Weeks Of Double-blind Treatment Research Articles

Safety and efficacy of continuous subcutaneous levodopa–carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial

Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson's disease. We conducted a phase 3, randomised, double-blind, double-dummy, active-controlled, multicentre trial at 117 academic and community neurology sites in 16 countries, including in Europe, Israel, and the USA. Eligible participants were men and women aged 30 years or older with a diagnosis of Parkinson's disease (Hoehn and Yahr stage ≤3 in the on state) who experienced at least 2·5 h/day of off time. Participants underwent an open-label run-in phase (<12 weeks), during which time optimal regimens were established for both oral immediate-release levodopa-carbidopa and for 24 h/day subcutaneous ND0612 infusion (levodopa-carbidopa 60·0/7·5 mg/mL), with supplemental oral levodopa-carbidopa if needed. Participants were then randomly assigned (1:1) to 12 weeks of double-blind treatment with their optimised regimen of either subcutaneous ND0612 or oral levodopa-carbidopa, with matching oral or subcutaneous placebo given as required to maintain blinding. Randomisation was done via an interactive web response system, stratified by region, using a permuted block schedule. Participants, study partners, treating investigators, study site personnel, and the sponsor were masked to treatment group allocation. The primary efficacy endpoint was the change from baseline (ie, time of randomisation, when all patients were receiving an optimised open-label ND0612 regimen) to end of the double-blind phase in total daily on time without troublesome dyskinesia, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT04006210, and is complete. Between Sept 30, 2019, and April 8, 2022, 381 participants were enrolled, of whom 259 (68%) were randomly assigned, 128 (49%) to subcutaneous ND0612 and 131 (51%) to oral levodopa-carbidopa. 243 (94%) participants completed the study. Treatment with subcutaneous ND0612 provided an additional 1·72 h (95% CI 1·08 to 2·36) of on time without troublesome dyskinesia compared with oral levodopa-carbidopa (change from baseline of -0·48 h [-0·94 to -0·02] with subcutaneous ND0612 vs -2·20 h [-2·65 to -1·74] with oral levodopa-carbidopa; p<0·0001). Significant treatment differences favouring subcutaneous ND0612 were also found in the first four of nine prespecified hierarchical outcomes of daily off time (-1·40 h [95% CI -1·99 to -0·80]), Movement Disorders Society-Unified Parkinson's Disease Rating Scale part II scores (-3·05 [-4·28 to -1·81]), Patients Global Impression of Change (odds ratio [OR] 5·31 [2·67 to 10·58]), and Clinical Global Impression of Improvement (OR 7·23 [3·57 to 14·64]). Hierarchical testing ended after the fourth secondary endpoint. Adverse events were reported by 287 (89%) of 322 participants during open-label ND0612 optimisation, and by 103 (80%) of 128 in the ND0612 group and 97 (74%) of 131 in the oral levodopa-carbidopa group during the double-blind phase. The most common adverse events were infusion-site reactions (266 [83%] participants during open-label ND0612, and 73 [57%] in the ND0612 group vs 56 [43%] in the oral levodopa-carbidopa group during the double-blind phase), most of which were mild. Serious adverse events in four participants in the ND0612 group were related to study treatment (infusion-site cellulitis [n=2], infusion-site abscess and infusion-site ulcer [n=1]; and paraesthesia and peripheral sensorimotor neuropathy [n=1]). One participant in the ND0612 group died during the double-blind phase, but the death was not related to study treatment (fall leading to traumatic brain injury). Results of this phase 3 study showed that subcutaneous ND0612 used in combination with oral immediate-release levodopa-carbidopa increased on time without troublesome dyskinesia and reduced off time, with a favourable benefit-risk profile. ND0612 might offer a safe and efficacious subcutaneous levodopa infusion approach to managing motor fluctuations in people with Parkinson's disease. The ongoing open-label extension phase will provide further information on the long-term efficacy and safety of treatment. NeuroDerm.

Efficacy and safety of cetagliptin as monotherapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial.

To assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D) and inadequate glycaemic control. In total, 504 eligible patients with T2D were enrolled and randomized to cetagliptin 50 mg once daily, cetagliptin 100 mg once daily or placebo at a ratio of 2:2:1 for 24 weeks of double-blind treatment, then all patients received cetagliptin 100 mg once daily for 28 weeks of open-label treatment. The primary efficacy endpoint was the change in HbA1c level from baseline at week 24. After 24 weeks, HbA1c from baseline was significantly reduced with cetagliptin 50 mg (-1.08%) and cetagliptin 100 mg (-1.07%) compared with placebo (-0.35%). The placebo-subtracted HbA1c reduction was -0.72% with cetagliptin 50 mg and 100 mg. Patients with a baseline HbA1c of 8.5% or higher had a greater HbA1c reduction with cetagliptin than those patients with a baseline HbA1c of less than 8.5%. Both doses studied led to a significantly higher proportion of patients (42.3% with 100 mg and 45.0% with 50 mg) achieving an HbA1c of less than 7.0% compared with placebo (12.9%). Cetagliptin also significantly lowered fasting plasma glucose and 2-hour postmeal plasma glucose relative to placebo. The incidence of adverse experiences was similar between cetagliptin and placebo. No drug-related hypoglycaemia was reported. Cetagliptin monotherapy was effective and well tolerated in Chinese patients with T2D who had inadequate glycaemic control on exercise and diet.

55-OR: HSK7653, a Novel Ultralong-Acting DPP-4 Inhibitor, as Monotherapy in Patients With Type 2 Diabetes—A Randomized, Double-Blind, Placebo-Controlled Phase III Trial

Background: HSK7653 is a novel ultralong-acting DPP-4 inhibitor that maintains the average plasma DPP-4 inhibition over 80% for 14 days after 10mg or 25mg dosing. This randomized, double-blind, placebo-controlled phase III trial was conducted to evaluate the efficacy and safety of HSK7653 biweekly as monotherapy for 52 weeks in drug naive type 2 diabetes patients with inadequate glycemic control on diet and exercise. Methods: A total of 475 patients with a mean HbA1c level of 8.1% were randomized to HSK7653 10mg, 25mg or placebo biweekly at a ratio of 1:1:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label extension treatment with HSK7653 25mg for all patients. The primary endpoint was the change in HbA1c from baseline at 24 weeks. Results: At week 24, the least-squares mean change in HbA1c from baseline was -0.96% in HSK7653 10mg, -0.92% in HSK7653 25mg and -0.33% in placebo. HSK7653 10mg and 25mg treatment resulted in significant placebo-subtracted changes in HbA1c of -0.63% (95% CI: -0.81%, -0.46%, p&amp;lt;0.0001) and -0.59% (95% CI: -0.77%, -0.42%, p&amp;lt;0.0001), respectively. The percentage of patients achieving HbA1c&amp;lt;7.0% was 44.2% in HSK7653 10mg group and 44.4% in HSK7653 25mg group versus 20.6% in placebo group (p&amp;lt;0.0001 for HSK7653 groups vs. placebo). No meaningful body weight changes were observed in all treatment groups. In the open-label extension treatment (from week 24 to week 52), the sustaining reduction of HbA1c from baseline were observed in HSK7653 10mg switched to 25mg group and HSK7653 25mg maintenance group. There were no excess hypoglycemia events in HSK7653 vs. placebo, and the incidence of adverse events was similar in all groups during the treatment. Conclusions: In people with type 2 diabetes who had inadequate glycemic control on diet and exercise, HSK7653 monotherapy significantly improved glycemic control with well tolerability and safety. Clinical trial information: NCT04556851. Disclosure L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck &amp; Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics. F.Bian: None. T.Pan: None. H.Jiang: None. C.Jiang: None. Q.Ren: None.

890-P: Efficacy and Safety of Dapagliflozin Add-on Therapy to Evogliptin plus Metformin Combinations in Inadequately Controlled Patients with Type 2 Diabetes—A 24-Week, Randomized, Double-blind, Placebo-Controlled, Parallel-Design, Phase 3 Trial

Background and Aims: We aimed to evaluate the efficacy and safety of dapagliflozin versus placebo as add-on therapy in patients with type 2 diabetes and inadequate glycemic control with evogliptin and metformin combinations. Materials and Methods: In this multi-center, double-blind, randomized, placebo-controlled phase 3 trial, patients with HbA1c ≥7.0% and ≤10.5% who had received stable-dose (≥1000 mg) metformin and evogliptin 5mg for at least 8 weeks were randomized to receive dapagliflozin 10mg or placebo once daily for 24 weeks. All patients continued treatment with metformin and evogliptin 5 mg. The primary endpoint was the change from baseline in HbA1c after 24 weeks of double-blind treatment. Results:198 patients were randomized and 195 patients were included in efficacy analyses (dapagliflozin: 96, placebo: 99). At week 24, dapagliflozin significantly reduced HbA1c. The least square [LS] mean difference in the change from baseline with dapagliflozin versus placebo was -0.70% (95% confidence interval [–0.91, –0.48], p&amp;lt;0.0001). The proportion of patients achieving HbA1c &amp;lt;7% was higher in dapagliflozin group (42.71% versus 16.16% in placebo; p=0.0002). Compared to placebo, dapagliflozin treatment significantly reduced fasting plasma glucose, mean daily glucose, fasting insulin and HOMA-IR at week 24. Adiponectin was significantly increased from baseline over 24 weeks with dapagliflozin. Adverse event rates were similar between groups (dapagliflozin: 27.55%, placebo:27.27%) including hypoglycemia and genital infection. Conclusions: Triple combination with dapagliflozin add-on to evogliptin plus metformin improved glycemic control and is well tolerated in patients with type 2 diabetes who are not adequately controlled with evogliptin and metformin combination. Disclosure I.Jeong: None. K.Choi: None. K.Han: None. K.Kim: None. I.Kim: None. S.Han: None. W.Lee: None. S.Yoo: None.

Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington's disease (KINECT-HD): a phase 3, randomised, double-blind, placebo-controlled trial

Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for treatment of tardive dyskinesia. To address the ongoing need for improved symptomatic treatments for individuals with Huntington's disease, valbenazine was evaluated for the treatment of chorea associated with Huntington's disease. KINECT-HD (NCT04102579) was a phase 3, randomised, double-blind, placebo-controlled trial, performed in 46 Huntington Study Group sites in the USA and Canada. The study included adults with genetically confirmed Huntington's disease and chorea (Unified Huntington's Disease Rating Scale [UHDRS] Total Maximal Chorea [TMC] score of 8 or higher) who were randomly assigned (1:1) via an interactive web response system (with no stratification or minimisation) to oral placebo or valbenazine (≤80 mg, as tolerated) for 12 weeks of double-blinded treatment. The primary endpoint was a least-squares mean change in UHDRS TMC score from the screening and baseline period (based on the average of screening and baseline values for each participant) to the maintenance period (based on the average of week 10 and 12 values for each participant) in the full-analysis set using a mixed-effects model for repeated measures. Safety assessments included treatment-emergent adverse events, vital signs, electrocardiograms, laboratory tests, clinical tests for parkinsonism, and psychiatric assessments. The double-blind placebo-controlled period of KINECT-HD has been completed, and an open-label extension period is ongoing. KINECT-HD was performed from Nov 13, 2019, to Oct 26, 2021. Of 128 randomly assigned participants, 125 were included in the full-analysis set (64 assigned to valbenazine, 61 assigned to placebo) and 127 were included in the safety-analysis set (64 assigned to valbenazine, 63 assigned to placebo). The full-analysis set included 68 women and 57 men. Least-squares mean changes from the screening and baseline period to the maintenance period in the UHDRS TMC score were -4·6 for valbenazine and -1·4 for placebo (least-squares mean difference -3·2, 95% CI -4·4 to -2·0; p<0·0001). The most commonly reported treatment-emergent adverse event was somnolence (ten [16%] with valbenazine, two [3%] with placebo). Serious treatment-emergent adverse events were reported in two participants in the placebo group (colon cancer and psychosis) and one participant in the valbenazine group (angioedema because of allergic reaction to shellfish). No clinically important ch anges in vital signs, electrocardiograms, or laboratory tests were found. No suicidal behaviour or worsening of suicidal ideation was reported in participants treated with valbenazine. In individuals with Huntington's disease, valbenazine resulted in improvement in chorea compared with placebo and was well tolerated. Continued research is needed to confirm the long-term safety and effectiveness of this medication throughout the disease course in individuals with Huntington's disease-related chorea. Neurocrine Biosciences.

0642 Effect of Iloperidone on Sleep Symptoms in Bipolar Patients with Manic and Mixed Episodes: A Randomized, Placebo Controlled Study

Abstract Introduction Iloperidone, a dopamine D2 receptor and serotonin 5HT2A receptor antagonist, was evaluated for the treatment of acute manic and mixed episodes associated with bipolar I disorder in adults in a phase 3 clinical trial. A core symptom of bipolar I disorder is disturbance in sleep. During manic episodes this commonly presents as reduced need for sleep with studies finding that 69%–99% of bipolar individuals report a lessened need for sleep or difficulties in falling and/or staying asleep. Here we present a post hoc analysis evaluating iloperidone effects on the sleep component of the Young Mania Rating Scale (YMRS) in patients with bipolar I disorder which addresses both sleep and the reduced need for sleep in that component. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study of iloperidone in patients with acute manic or mixed episodes associated with bipolar I disorder. Patients received four weeks of double-blind treatment. The primary analysis demonstrating an overall improvement from baseline YMRS score in iloperidone assigned patients versus placebo assigned patients (p = 0.000008) at the end of the study (week 4). A YMRS item level analysis evaluated changes on YMRS single items including the sleep component in the intent-to-treat population (N = 392) using a mixed-effects model for repeated measures approach. Results The least squares mean difference (LSMD) in change from baseline to day 28 was statistically significant on the YMRS sleep component in favor of iloperidone versus placebo (iloperidone = -1.26, placebo = -0.95; p = 0.008). Conclusion In addition to improving overall mania symptoms as reported by the YMRS, improvements were also seen in iloperidone treated patients in the sleep component which at baseline included assessments of both decreased sleep and decreased need or denial of the need for sleep. Support (if any) This work was supported by Vanda Pharmaceuticals Inc.

Medication Preference, Satisfaction, and Clinical Improvement Among Adults Receiving Long-Term Treatment With Rimegepant for Migraine (P10-12.011)

<h3>Objective:</h3> Assess preference for and satisfaction with rimegepant as well as clinical global impression of change (CGI-C) over a 1-year open-label extension (OLE) phase in which rimegepant was used for both preventive and acute treatment of migraine. <h3>Background:</h3> Rimegepant is an orally administered small molecule CGRP receptor antagonist for the acute and preventive treatment of migraine. <h3>Design/Methods:</h3> This 1-year OLE phase of a 12-week, phase 2/3, randomized, double-blind, placebo-controlled study (NCT03732638) included adults aged ≥18 years with a history of 4 to 18 moderate to severe monthly migraine attacks. Subjects who completed 12 weeks of double-blind treatment with rimegepant 75 mg or placebo every other day could continue with open-label treatment with rimegepant 75 mg every other day for preventive treatment of migraine for 52 weeks. On nonscheduled dosing days, subjects could take rimegepant 75 mg up to once per day as needed for acute treatment of migraine. Exploratory objectives in this study included evaluating the effect of rimegepant on Preference of Medication (PoM), Satisfaction with Medication (SM), and CGI-C. The PoM, SM, and CGI-C were evaluated at Weeks 12 and 52 of the OLE phase (ie, overall study Weeks 24 and 64), and percentages (95% CIs) were calculated. <h3>Results:</h3> At Week 12 (n=357) and Week 52 (n=246), respectively, 82.6% (78.3, 86.2) and 85.2% (80.4, 89.0) of subjects preferred rimegepant to previous migraine treatments; 32.7% (28.2, 37.6) and 47.2% (41.5, 53.0) of subjects were completely satisfied with rimegepant (a majority of the remaining subjects were very satisfied); and 95.1% (92.9, 96.7) and 98.3% (96.4, 99.2) of subjects were considered improved on the CGI-C scale. <h3>Conclusions:</h3> With long-term dosing of open-label rimegepant for both preventive treatment and acute treatment of migraine, the vast majority of subjects preferred rimegepant to prior migraine medications, were satisfied with rimegepant, and experienced clinical improvement. <b>Disclosure:</b> Dr. Mullin has received personal compensation in the range of $0-$499 for serving as a Consultant for Vorso. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Mullin has received personal compensation in the range of $0-$499 for serving as a Consultant for Theranica. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eli Lilly. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biohaven. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Pavlovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alder Pharmaceutical. Susan Hutchinson has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Allergan Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen Pharmaceutical. Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biohaven . Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Currax Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for electroCore. Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lilly Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $0-$499 for serving as a Consultant for Lundbeck Pharmaceutical. Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Upsher Smith. Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan . Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Allergan/AbbVie. Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen. Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biohaven . Susan Hutchinson has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Lilly Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lundbeck . Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva . Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Headache Cooperative of the Pacific . Susan Hutchinson has received publishing royalties from a publication relating to health care. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Dr. Jensen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Dr. Jensen has stock in Biohaven Pharmaceuticals. Alexandra Thiry has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Alexandra Thiry has received stock or an ownership interest from Biohaven Pharmaceuticals. Lisa Kamen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc.. Lisa Kamen has received stock or an ownership interest from Biohaven Pharmaceuticals, Inc.. Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.

Patterns of Medication Utilization and Migraine Frequency in Adults Using Rimegepant for Both Preventive and Acute Treatment for Migraine: Results From a 52-Week, Open-Label Extension Study (P9-12.006)

<h3>Objective:</h3> Assess use of rimegepant and other medications for acute treatment of migraine, as well as frequency of moderate or severe migraine days on scheduled and nonscheduled rimegepant dosing days. <h3>Background:</h3> Rimegepant is an orally administered small molecule CGRP receptor antagonist and is the only medication approved for both acute and preventive treatment of migraine. <h3>Design/Methods:</h3> This 52-week open-label extension phase of a 12-week, phase 2/3, randomized, double-blind, placebo-controlled study of rimegepant for the preventive treatment of migraine (NCT03732638) included adults aged ≥18 years with a history of 4–18 moderate to severe monthly migraine attacks. Subjects completing 12 weeks of double-blind treatment with rimegepant 75 mg or placebo every other day (QOD) could continue with open-label rimegepant 75 mg scheduled QOD for preventive treatment of migraine over 52 weeks. On nonscheduled rimegepant dosing days, subjects could take rimegepant 75 mg up to once per day as needed for acute treatment. Subjects received 30 rimegepant tablets per month. Subjects could also use other medications for the acute treatment of migraine on scheduled and nonscheduled dosing days if needed. Months were defined as 4-week intervals. <h3>Results:</h3> Through 52 weeks, subjects used rimegepant a mean (SD) of 14.2 (1.90) days per month. On scheduled and nonscheduled rimegepant dosing days over 52 weeks, mean (SD) moderate or severe migraine days per month were 1.4 (1.71) and 1.4 (1.63), respectively, and mean (SD) other acute migraine medication days per month were 0.6 (1.09) and 0.6 (1.08), respectively. On nonscheduled rimegepant dosing days, subjects used rimegepant as an acute migraine medication a mean (SD) of 1.1 (1.53) days per month and rimegepant plus other acute migraine medication 0.2 (0.59) days per month. <h3>Conclusions:</h3> The monthly frequency of moderate or severe migraine days and use of other acute migraine medications was low and consistent between scheduled and nonscheduled rimegepant dosing days. <b>Disclosure:</b> Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alder Pharmaceutical. Susan Hutchinson has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Allergan Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen Pharmaceutical. Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biohaven . Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Currax Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for electroCore. Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lilly Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $0-$499 for serving as a Consultant for Lundbeck Pharmaceutical. Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Upsher Smith. Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan . Susan Hutchinson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Allergan/AbbVie. Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen. Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biohaven . Susan Hutchinson has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Lilly Pharmaceutical . Susan Hutchinson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lundbeck . Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva . Susan Hutchinson has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Headache Cooperative of the Pacific . Susan Hutchinson has received publishing royalties from a publication relating to health care. Dr. Mullin has received personal compensation in the range of $0-$499 for serving as a Consultant for Vorso. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Mullin has received personal compensation in the range of $0-$499 for serving as a Consultant for Theranica. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eli Lilly. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biohaven. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Pavlovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Dr. Jensen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Dr. Jensen has stock in Biohaven Pharmaceuticals. Alexandra Thiry has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Alexandra Thiry has received stock or an ownership interest from Biohaven Pharmaceuticals. Lisa Kamen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc.. Lisa Kamen has received stock or an ownership interest from Biohaven Pharmaceuticals, Inc.. Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.

Supplementation with inulin-type fructans affects gut microbiota and attenuates some of the cardiometabolic benefits of a plant-based diet in individuals with overweight or obesity.

The gut microbiota has emerged as a potential therapeutic target to improve the management of obesity and its comorbidities. We investigated the impact of a high fiber (∼38 g/d) plant-based diet, consumed ad libitum, with or without added inulin-type fructans (ITF), on the gut microbiota composition and cardiometabolic outcomes in subjects with obesity. We also tested if baseline Prevotella/Bacteroides (P/B) ratio predicts weight loss outcomes. This is a secondary exploratory analysis from the PREVENTOMICS study, in which 100 subjects (82 completers) aged 18-65 years with body mass index 27-40 kg/m2 were randomized to 10 weeks of double-blinded treatment with a personalized or a generic plant-based diet. Changes from baseline to end-of-trial in gut microbiota composition (16S rRNA gene amplicon sequencing), body composition, cardiometabolic health and inflammatory markers were evaluated in the whole cohort (n = 82), and also compared in the subgroup of subjects who were supplemented with an additional 20 g/d ITF-prebiotics (n = 21) or their controls (n = 22). In response to the plant-based diet, all subjects lost weight (-3.2 [95% CI -3.9, -2.5] kg) and experienced significant improvements in body composition and cardiometabolic health indices. Addition of ITF to the plant-based diet reduced microbial diversity (Shannon index) and selectively increased Bifidobacterium and Faecalibacterium (q < 0.05). The change in the latter was significantly associated with higher values of insulin and HOMA-IR and lower HDL cholesterol. In addition, the LDL:HDL ratio and the concentrations of IL-10, MCP-1 and TNFα were significantly elevated in the ITF-subgroup. There was no relationship between baseline P/B ratio and changes in body weight (r = -0.07, p = 0.53). A plant-based diet consumed ad libitum modestly decreases body weight and has multiple health benefits in individuals with obesity. Addition of ITF-prebiotics on top this naturally fiber-rich background selectively changes gut microbiota composition and attenuates some of the realized cardiometabolic benefits. [https://clinicaltrials.gov/ct2/show/NCT04590989], identifier [NCT04590989].

Long-Term Preventive and Acute Treatment of Migraine With Rimegepant Improves Health Related Quality of Life (P12-12.003)

<h3>Objective:</h3> Assess the effects of rimegepant on quality of life (QoL) over 1-year of open-label treatment in which rimegepant was used for both preventive and acute treatment for migraine. <h3>Background:</h3> Rimegepant is an orally administered small molecule CGRP receptor antagonist for the acute and preventive treatment of migraine. <h3>Design/Methods:</h3> This open-label extension phase of a 12-week, phase 2/3, randomized, double-blind, placebo-controlled study (NCT03732638) enrolled adults aged ≥18 years with a history of 4–18 moderate to severe monthly migraine attacks. Subjects completing 12 weeks of double-blind treatment with rimegepant 75 mg or placebo every other day could continue with open-label treatment with rimegepant 75 mg for 52 weeks of preventive treatment. On nonscheduled dosing days, subjects could take open-label rimegepant 75 mg as needed up to once per day for acute treatment of migraine. The effects of rimegepant on QoL were measured using Migraine-Specific Quality-of-Life Questionnaire v 2.1 (MSQ) scores on the role restrictive (RR), role preventative (RP), and emotional function (EF) domains. Changes from baseline in MSQ domain scores were assessed at Weeks 12 and 52 of the open-label phase (ie, overall study Weeks 24 and 64). Higher MSQ scores indicated better quality of life. <h3>Results:</h3> Respective mean (SD) baseline MSQ scores for the RR, RP, and EF domains were 51.0 (18.70), 65.2 (21.01), and 57.7 (27.23). At Week 12 (n=536) mean (SD) changes from baseline in RR, RP, and EF, respectively, were 28.4 (22.71), 21.8 (21.46), and 27.4 (26.58); at Week 52 (n=398), they were 32.9 (21.46) for RR, 25.1 (21.66) for RP, and 30.1 (26.40) for EF. <h3>Conclusions:</h3> Long-term treatment with oral rimegepant 75 mg taken every other day for preventive treatment and up to once daily on nonscheduled days as needed for acute treatment was associated with improvements in migraine-specific QoL. <b>Disclosure:</b> Dr. Pavlovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Turner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan, Amgen, Novartis, Teva, Lilly, Lundbeck, Biohaven,Impel. Dr. Turner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen, Teva, Allergan, Biohaven, Lilly, Lundbeck, Theranica, Revance. Dr. Turner has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Allergan, Amgen, Biohaven, Teva, Novartis, Lundbeck, Lilly. The institution of Dr. Turner has received research support from Allergan, Amgen, Biohaven, Lilly, Lundbeck, Theranica. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck . Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen. Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Allergan. Dr. Winner has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lundbeck. Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Winner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for lilly. The institution of Dr. Winner has received research support from Amgen. The institution of Dr. Winner has received research support from Allergan. The institution of Dr. Winner has received research support from Lundbeck . The institution of Dr. Winner has received research support from Novartis. The institution of Dr. Winner has received research support from Lilly. The institution of Dr. Winner has received research support from Teva. The institution of Dr. Winner has received research support from Supernus. The institution of Dr. Winner has received research support from Biogen. The institution of Dr. Winner has received research support from Avinar. The institution of Dr. Winner has received research support from SAMUS. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Gilbert J. L’Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L’Italien has received stock or an ownership interest from biohaven pharmaceuticals. Dr. Jensen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Dr. Jensen has stock in Biohaven Pharmaceuticals. Alexandra Thiry has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Alexandra Thiry has received stock or an ownership interest from Biohaven Pharmaceuticals. Lisa Kamen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc.. Lisa Kamen has received stock or an ownership interest from Biohaven Pharmaceuticals, Inc.. Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.

Safety and Tolerability of Rimegepant Every Other Day for Preventive Treatment of Migraine Plus As-Needed for Acute Treatment of Migraine: Results from A 52-Week, Open-Label Extension Phase (P12-12.006)

<h3>Objective:</h3> Assess the safety and tolerability of rimegepant 75 mg dosed every other day (EOD) for the preventive treatment of migraine and as-needed (PRN) for acute treatment on nonscheduled dosing days. <h3>Background:</h3> Rimegepant is an orally administered small molecule CGRP receptor antagonist indicated for the acute and preventive treatment of migraine. <h3>Design/Methods:</h3> This open-label extension phase of a 12-week, phase 2/3, randomized, double-blind, placebo-controlled study (NCT03732638) included adults aged ≥18 years with a history of 4–18 moderate to severe monthly migraine attacks. Subjects completing 12 weeks of double-blind treatment with rimegepant 75 mg or placebo EOD could continue with rimegepant 75 mg EOD for preventive treatment of migraine for 52 weeks. On nonscheduled dosing days, subjects could take rimegepant 75 mg up to once per day PRN for acute treatment of migraine. Subjects who took ≥1 dose of open-label rimegepant were analyzed. Months were defined as 4-week intervals. <h3>Results:</h3> Of the 741 subjects who received double-blind treatment, 603 (81.4% [rimegepant n=301, placebo n=302]) were treated in the open-label extension. The most common AEs were upper respiratory tract infection (7.1%), nasopharyngitis (6.3%), and back pain (4.3%). The rate of discontinuation due to AEs was 2.8%. Serious AEs in 2.2% of subjects were considered not related to rimegepant. Two deaths (0.3%), 1 due to aortic dissection related to Marfan syndrome and 1 due to sepsis, were also deemed unrelated to rimegepant. Aminotransferases &gt;3× the upper limit of normal (ULN) occurred in 3.4% of subjects; none had concurrent elevations in bilirubin &gt;2× ULN. Subjects took a mean (SD) of 14.6 (2.45) rimegepant doses per month; 81.4% used ≤16 rimegepant tablets per month. <h3>Conclusions:</h3> One year of open-label rimegepant 75 mg dosed EOD for preventive treatment of migraine plus PRN on nonscheduled dosing days for acute treatment was safe and well tolerated, with no new safety concerns identified. <b>Disclosure:</b> Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Dr. Kudrow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Kudrow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Kudrow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Kudrow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Kudrow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Kudrow has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen. Dr. Kudrow has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eli Lilly. Dr. Kudrow has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Kudrow has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Allergan. Dr. Kudrow has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lundbeck. Dr. Kudrow has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biohaven. The institution of Dr. Smith has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Nocira. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vorso/Nesos. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alder/Lundbeck. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. The institution of Dr. Smith has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. The institution of Dr. Smith has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurolief. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Nocira. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theranica. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. The institution of Dr. Smith has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Abbvie/Allergan. The institution of Dr. Smith has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biohaven. The institution of Dr. Smith has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lilly. Dr. Smith has stock in United Health Group. The institution of Dr. Smith has received research support from Aeon. The institution of Dr. Smith has received research support from Alder/Lundbeck. The institution of Dr. Smith has received research support from Alnylam. The institution of Dr. Smith has received research support from Amgen. The institution of Dr. Smith has received research support from Abbvie/Allergan. The institution of Dr. Smith has received research support from Biohaven. The institution of an immediate family member of Dr. Smith has received research support from Eliem Pharmaceuticals. The institution of Dr. Smith has received research support from Lilly. The institution of Dr. Smith has received research support from Pfizer. The institution of Dr. Smith has received research support from Nocira. The institution of Dr. Smith has received research support from Novo Nordisk. The institution of Dr. Smith has received research support from Teva. The institution of Dr. Smith has received research support from Theranica. The institution of Dr. Smith has received research support from Vorso/Nesos. Dr. Smith has a non-compensated relationship as a Board Member with National Headache Foundation that is relevant to AAN interests or activities. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Allergan/Abbvie. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck/Alder. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Impel. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nesos. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GlaxoSmithKline. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiodeliveryScienceIndustry. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Miravo. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theranica. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Satsuma. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeon. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Axsome. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lindpharma. Dr. Ailani has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Pain and Headache Report. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Live. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medscape. Dr. Ailani has stock in Ctrl M. The institution of Dr. Ailani has received research support from Allergan/Abbvie. The institution of Dr. Ailani has received research support from Eli Lilly. The institution of Dr. Ailani has received research support from Zosano. Dr. Ailani has received research support from Satsuma. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Advisory Panel with Medscape. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Medical Advisor with SELF. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aeon BioPharmaceuticals. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven Pharmaceuticals. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli-Lilly. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epalex. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel Neuropharma. Dr. Goadsby has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dr Reddys. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biodelivery Sciences International. Dr. Goadsby has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeon Biopharma. Dr. Goadsby has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Massachusetts Medical Society. The institution of Dr. Goadsby has received research support from Celgene. The institution of Dr. Goadsby has received research support from Eli-Lilly. The institution of Dr. Goadsby has received research support from Visual Snow Initiative. Dr. Goadsby has received publishing royalties from a publication relating to health care. Dr. Goadsby has received publishing royalties from a publication relating to health care. Dr. Goadsby has a non-compensated relationship as a Trustee with Migraine Trust that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Trustee with Organisation for Understanding Cluster Headache (UK) that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Executive roles with American Headache Society that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Scientific Officer with British Association for the Study of Headache that is relevant to AAN interests or activities. Dr. Goadsby has a non-compensated relationship as a Director with American Migraine Foundation that is relevant to AAN interests or activities. Lisa Kamen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc.. Lisa Kamen has received stock or an ownership interest from Biohaven Pharmaceuticals, Inc.. Alexandra Thiry has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Alexandra Thiry has received stock or an ownership interest from Biohaven Pharmaceuticals. Dr. Jensen has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Dr. Jensen has stock in Biohaven Pharmaceuticals. Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.

Adjunctive Cariprazine in Patients With Major Depressive Disorder: Post Hoc Analysis of Efficacy by Baseline Antidepressant Response

AbstractIntroductionPatients with major depressive disorder (MDD) often have inadequate response to antidepressant treatment (ADT) requiring augmentation with other treatments. Cariprazine is a D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat schizophrenia and manic, mixed, and depressive episodes of bipolar I disorder. The efficacy of cariprazine as an adjunctive treatment for patients with MDD and inadequate response to ADT alone has been evaluated in phase 2/3 randomized, double-blind, placebo-controlled trials. Post hoc analyses of one phase 3 trial (NCT03738215) evaluated cariprazine + ADT for improving depressive symptoms in subgroups of patients categorized by 1) the level of response to ongoing ADT at baseline and 2) the number of ADTs associated with inadequate response during the current episode.MethodsPatients were randomized to placebo + ADT (n=254), cariprazine 1.5 mg/d + ADT (n=252), or cariprazine 3 mg/d + ADT (n=253) for 6 weeks of double-blind treatment. Post hoc analyses evaluated change from baseline to week 6 in MADRS total score in subgroups of patients who had ≥25%–&lt;50% or &lt;25% response to ongoing ADT at baseline, and in subgroups of patients who had inadequate response to 1 or ≥2 ADTs in the current episode. Analyses used a mixed-effects model for repeated measures; least squares mean differences (LSMD) versus placebo with 95% confidence interval (95% CI) were calculated.ResultsAt baseline, 65.1% (n=486) of patients had an ADT response level between 25%–&lt;50% and 34.9% (n=261) of patients had an ADT response level &lt;25%. Mean MADRS total score reductions were greater for cariprazine 1.5 mg/d + ADT versus placebo + ADT in both ADT response subgroups (25%–&lt;50% ADT response: -14.8 vs -11.9, LSMD [95% CI]=-2.3 [-4.2, -0.3]; &lt;25% response to ADT: (-14.7 vs -11.7, LSMD [95% CI]=-2.6 [-5.5, 0.3]). For cariprazine 3 mg/d + ADT, mean change in MADRS total score was numerically greater versus placebo in both response subgroups (25%–&lt;50% response=-14.2, LSMD [95% CI]=-1.5 [-3.5, 0.4]; &lt;25% response= -12.3, LSMD [95% CI]=-0.74 [-3.6, 2.1]). Approximately 86% (n=644) and 14% (n=105) of patients in this study had inadequate response to 1 ADT or ≥2 ADTs, respectively, during the current episode. The LSMD (95% CI) in MADRS total score change for cariprazine 1.5 mg/d + ADT versus placebo + ADT was -2.3 (-4.1, -0.6) in the subgroup of patients with 1 previous ADT and -3.2 [-7.1, 0.8]) in the subgroup of patients with ≥2 previous ADTs. For cariprazine 3 mg/d + ADT, the LSMD (95% CI) in MADRS total score change versus placebo was -0.7 (-2.5, 1.0) in the 1 previous ADT subgroup and -4.7 (-8.8, -0.6) in the ≥2 previous ADTs subgroup.ConclusionsIn these post hoc analyses, cariprazine + ADT was associated with greater reductions in MADRS total score versus placebo regardless of the level of response to ongoing ADT at baseline or number of prior ADT failures in the current episode.FundingAbbVie

Lurasidone and risk of metabolic syndrome: results from short and long-term studies in patients with bipolar depression.

The elevated prevalence of metabolic syndrome (MetS) in patients with depression has been associated with increased mortality. This post hoc analysis assessed the effect of treatment with lurasidone on risk of MetS in patients with bipolar depression. Data used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (N=1192), consisting of 1 monotherapy, and 2 adjunctive trials (lithium or valproate). Also analyzed was a 6-month open-label (OL) extension study (monotherapy, N=316; adjunctive therapy, N=497); and a 5-month, OL, stabilization phase followed by randomization to a 28-week DB, placebo-controlled, adjunctive therapy study with lurasidone (N=490). MetS was defined based on NCEP ATP III criteria (2005 revision). The proportion of patients with new-onset MetS was similar for lurasidone vs placebo in the short-term studies (monotherapy, 13.9% vs 15.3%; adjunctive therapy, 13.6% vs 11.0%); and remained stable during both the 6-month extension phase study (monotherapy, 15.2%; adjunctive therapy, 16.9%), and the 5-month stabilization study (adjunctive therapy, 12.2%). After 28weeks of DB treatment (following 5-month treatment in the stabilization study), new onset MetS was observed at endpoint (OC) in 26.2% of the lurasidone group, and 30.8% of the placebo group. This post hoc analysis found that both short and long-term treatment with lurasidone was associated with a relatively low risk for the development of MetS in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.

Atorvastatin Metabolite Pattern in Skeletal Muscle and Blood from Patients with Coronary Heart Disease and Statin-Associated Muscle Symptoms.

Self-perceived statin-associated muscle symptoms (SAMS) are prevalent, but only a minority is drug-dependent. Diagnostic biomarkers are not yet identified. The local statin exposure in skeletal muscle tissue may correlate to the adverse effects. We aimed to determine whether atorvastatin metabolites in blood reflect the corresponding metabolite levels in skeletal muscle, and whether genetic variants of statin transporters modulate this relationship. We also addressed atorvastatin metabolites as potential objective biomarkers of SAMS. Muscle symptoms were examined in patients with coronary disease and self-perceived SAMS during 7 weeks of double-blinded treatment with atorvastatin 40 mg/day and placebo in randomized order. A subset of 12 patients individually identified with more muscle symptoms on atorvastatin than placebo (confirmed SAMS) and 15 patients with no difference in muscle symptom intensity (non-SAMS) attended the present follow-up study. All received 7 weeks of treatment with atorvastatin 40 mg/day followed by 8 weeks without statins. Biopsies from the quadriceps muscle and blood plasma were collected after each treatment period. Strong correlations (rho > 0.7) between muscle and blood plasma concentrations were found for most atorvastatin metabolites. The impact of the SLCO1B1 c.521T>C (rs4149056) gene variant on atorvastatin's systemic pharmacokinetics was translated into muscle tissue. The SLCO2B1 c.395G>A (rs12422149) variant did not modulate the accumulation of atorvastatin metabolites in muscle tissue. Atorvastatin pharmacokinetics in patients with confirmed SAMS were not different from patients with non-SAMS. In conclusion, atorvastatin metabolite levels in skeletal muscle and plasma are strongly correlated, implying that plasma measurements are suitable proxies of atorvastatin exposure in muscle tissue. The relationship between atorvastatin metabolites in plasma and SAMS deserves further investigation.

Energy Trial in Warm Autoimmune Hemolytic Anemia (wAIHA): Design of a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nipocalimab, an FcRn Blocker

Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare condition characterized by the premature destruction of red blood cells (RBCs) mainly in the presence of pathogenic immunoglobulin G (IgG) autoantibodies that preferentially bind to RBCs at 37°C, resulting in extravascular hemolysis of these RBCs in the spleen (or liver). Patients with wAIHA can experience acute or chronic worsening of anemia, increased risk of thromboembolic events, and premature death. Innovative targeted therapies that address the underlying pathogenesis of wAIHA are needed, as there is currently no approved treatment for this disease. Nipocalimab is a high affinity, fully human, aglycosylated, effectorless IgG1 monoclonal antibody that targets the neonatal Fc receptor (FcRn) to lower circulating IgG levels, including pathogenic autoantibodies. Nipocalimab is being evaluated across multiple IgG-mediated diseases. A completed phase 2 study in patients with generalized myasthenia gravis demonstrated rapid, durable total serum IgG and pathogenic IgG autoantibody reductions and meaningful clinical response [Guptill J, et al. AAN 2021. Presentation 2157]. Aim: Describe the rationale and study design of ENERGY, an ongoing, adaptive, phase 2/3 multicenter, randomized, double-blind, placebo-controlled study that will evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of nipocalimab compared with placebo in patients with wAIHA (NCT04119050). Methods: Subjects ≥18 years of age who have been diagnosed with primary or secondary wAIHA and are currently receiving treatment for wAIHA or have previously received treatment for wAIHA will be included in the study. Subjects with cold antibody AIHA, cold agglutinin syndrome, mixed type (i.e., warm and cold) AIHA, or paroxysmal cold hemoglobinuria will be excluded. Stable doses of corticosteroids or immunosuppressants will be allowed. Approximately 111 patients will be randomized 1:1:1 to receive nipocalimab at two different dose schedules or placebo. Following completion of 24 weeks of double-blind treatment, patients may enter an open-label extension period to receive nipocalimab for 144 weeks with a follow-up period of 6 weeks after last assessment. Results: ENERGY will include approximately 160 sites across 19 countries, including Brazil, Canada, China, Czech, Egypt, France, Germany, Greece, Hungary, Japan, Israel, Malaysia, Netherlands, Italy, Poland, South Korea, Spain, the United Kingdom, and the United States. The primary endpoint is percentage of participants achieving durable response of improvement in hemoglobin (Hgb). The secondary endpoints include change from baseline in the total score from the Functional Assessment of Chronic Illness Therapy-Fatigue Scale, corticosteroid dose reduction from baseline, and normalization of hemolytic markers. Conclusion/Summary: The results of ENERGY have the potential to identify a novel treatment option to address the significant unmet needs of patients with wAIHA. Enrollment is ongoing in this clinical trial.

The efficacy and safety of macitentan in Fontan-palliated patients: results of the 52-week randomised, placebo-controlled RUBATO trial

Abstract Background The clinical utility and long-term effects of endothelin receptor antagonists (ERAs) in Fontan-palliated patients remain unclear and there are currently no approved therapies. A decline in peak VO2 between consecutive cardiopulmonary exercise tests (CPETs) is highly prognostic for death or transplant in adult Fontan patients, hence its use as a primary endpoint in clinical trials of ERAs in patients with Fontan circulation. Purpose The RUBATO trial aimed to assess the efficacy and safety of macitentan, an endothelin receptor antagonist, in Fontan-palliated patients over 52 weeks. Methods In the multicentre, double-blind, randomised, placebo-controlled, phase 3 RUBATO trial, Fontan-palliated patients were randomised 1:1 to macitentan 10 mg once-daily or placebo for 52 weeks. Eligible patients were aged ≥12 years, in New York Heart Association functional class II or III, had no limitations for CPET (including no pacemakers), had undergone lateral tunnel or extracardiac conduit Fontan (total cavopulmonary connection) &amp;gt;1 year before screening and showed no signs of Fontan failure or clinical deterioration within 3 months before screening. Primary efficacy endpoint was change in peak VO2 from baseline to week 16. Secondary endpoints were change in peak VO2 from baseline over 52 weeks and change in mean count per minute of daily physical activity from baseline to week 16 as measured by an accelerometer. Adverse events were also assessed. Results 137 patients were randomised to macitentan (n=68) or placebo (n=69). 92.7% of patients completed 52 weeks of double-blind treatment: 7 and 3 patients prematurely discontinued study treatment in macitentan and placebo arms, respectively. Patient baseline characteristics are shown in Table 1. At week 16, the mean (SD) change from baseline in peak VO2 was –0.16 (2.86) with macitentan vs –0.67 (2.66) mL/kg/min with placebo (median unbiased estimate of the difference between macitentan and placebo: 0.62 mL/kg/min [99% repeated confidence interval –0.62; 1.85], p=0.1930). No treatment effect was observed in the two secondary endpoints (Table 2): mean (SD) count per minute of daily physical activity decreased from baseline to week 16 by 3.02 (92.44) with macitentan and by 14.34 (117.56) with placebo (p=0.4512). The most common AEs were headache (10.3% vs 8.7% on placebo), nasopharyngitis (5.9% vs 4.3%), and pyrexia (5.9% vs 4.3%). AEs leading to treatment discontinuation were reported in 3 (4.4%) and 1 (1.4%) of macitentan and placebo patients. Conclusion The 52-week RUBATO trial provides an important addition to data on the clinical utility of ERAs in Fontan-palliated patients. The primary efficacy endpoint was not met and no treatment effect was observed for the two secondary endpoints. Macitentan was well tolerated; safety findings were consistent with the known safety profile of macitentan 10 mg. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson &amp; Johnson.

PRIOR SPECIALIST CONSULTATIONS AND TREATMENTS IN A REFRACTORY CHRONIC COUGH POPULATION ENROLLED IN A PHASE 2B STUDY OF THE P2X3 ANTAGONIST BLU-5937

SESSION TITLE: Signs and Symptoms of Chest Disease Abstract PostersSESSION TYPE: Original Investigation PostersPRESENTED ON: 10/18/2022 01:30 pm - 02:30 pmPURPOSE: The lack of approved treatment for refractory chronic cough (RCC) increases the burden on patients by resulting in multiple cycles of medical consultations, diagnostic investigations and trials of therapy. The development of P2X3 antagonists for the treatment of RCC has opened the possibility to alleviate this burden in the future. To better understand the current experience of RCC patients, we report the prior specialty consultations and treatments in a RCC population enrolled in a phase 2b study of BLU-5937, a selective P2X3 antagonist.METHODS: SOOTHE (NCT04678206) was a multi-center phase 2b, randomized, placebo-controlled, parallel arm clinical dose-finding study in participants diagnosed with RCC for ≥1 year and with an awake cough frequency ≥25 coughs/h. Patients included also had to report a cough severity of at least 40 mm on a 100 mm visual analog scale. A FEV1/FVC score of at least 60% was also necessary for inclusion. Patients with a diagnosis of COPD, bronchiectasis or IPF were excluded from the study. Prohibited medications during the study included anti-tussive therapy, gabapentin, pregabalin, baclofen, tricyclic antidepressants, systemic corticosteroids and ACE inhibitors. Following a single-blind run-in period, 249 participants who had maintained a baseline awake cough frequency ≥25 coughs/h were randomized 1:1:1:1 to the three active treatment arms of BLU-5937 (12.5, 50 and 200 mg BID) or placebo for 4 weeks of double-blind treatment.RESULTS: Ninety-four percent of patients enrolled in SOOTHE had seen at least one specialist prior to the study. Pulmonologists were the specialists most often consulted, with 78% of participants having seen at least one. Moreover, 59% had consulted with an ENT specialist, 50% with an allergist or immunologist and 46% with a gastroenterologist. A speech language pathologist had been seen by 16% of participants. Patients enrolled in the main population of SOOTHE had received an average of 5.2 ±3.1 treatments related to their cough prior to the start of the trial. Interestingly, 31% were diagnosed with asthma but 73% had received at least one prior treatment for the condition; 46% were diagnosed with GERD but 77% had received at least one prior treatment; 26% were diagnosed with UACS but 70% had received at least one prior treatment. Overall, the most common prior medications included acid reducers (76%), inhaled bronchodilators (56%) and oral antihistamines (51%).CONCLUSIONS: Overall, the broad range of specialists seen by RCC patients reflect the evaluation needed to establish the diagnosis.CLINICAL IMPLICATIONS: The large number of specialists consulted, and treatments attempted demonstrate the burden put on patients and healthcare systems by RCC.DISCLOSURES: Consultant relationship with Bellus Please note: 3/19-current Added 03/25/2022 by Michael Blaiss, value=HonorariaSpeaker/Speaker's Bureau relationship with Merck Please note: 3/19-current Added 03/25/2022 by Michael Blaiss, value=Honorariano disclosure submitted for Catherine Bonuccelli;Consultant relationship with Merck Please note: 2017-2021 by Peter Dicpinigaitis, value=Consulting feeConsultant relationship with Bayer Please note: 2019-2021 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting feeConsultant relationship with Bellus Please note: 2019-2022 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting feeConsultant relationship with Bellus Please note: 2019-2022 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting feeRemoved 03/25/2022 by Peter DicpinigaitisConsultant relationship with Shionogi Please note: 2019-2022 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting feeConsultant relationship with Chiesi Please note: 2020-2022 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting feeEmployeeNo relevant relationships by Vivek IyerEmployee relationship with Bellus Health Please note: 2020-2022 Added 03/16/2022 by Sylvain Lanouette, value=SalaryConsultant relationship with Bellus Health Please note: 2020-2022 Added 03/26/2022 by Lorcan McGarvey, value=Consulting feeScientific Medical Advisor relationship with Merck Please note: $1001 - $5000 by Jaclyn Smith, value=Consulting feeScientific Medical Advisor relationship with Vitalograph Ltd Please note: $5001 - $20000 by Jaclyn Smith, value=Grant/Research SupportGrant Funding relationship with Merck Please note: 2020-2022 by Jaclyn Smith, value=Grant/Research SupportConsultantEmployee SESSION TITLE: Signs and Symptoms of Chest Disease Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: The lack of approved treatment for refractory chronic cough (RCC) increases the burden on patients by resulting in multiple cycles of medical consultations, diagnostic investigations and trials of therapy. The development of P2X3 antagonists for the treatment of RCC has opened the possibility to alleviate this burden in the future. To better understand the current experience of RCC patients, we report the prior specialty consultations and treatments in a RCC population enrolled in a phase 2b study of BLU-5937, a selective P2X3 antagonist. METHODS: SOOTHE (NCT04678206) was a multi-center phase 2b, randomized, placebo-controlled, parallel arm clinical dose-finding study in participants diagnosed with RCC for ≥1 year and with an awake cough frequency ≥25 coughs/h. Patients included also had to report a cough severity of at least 40 mm on a 100 mm visual analog scale. A FEV1/FVC score of at least 60% was also necessary for inclusion. Patients with a diagnosis of COPD, bronchiectasis or IPF were excluded from the study. Prohibited medications during the study included anti-tussive therapy, gabapentin, pregabalin, baclofen, tricyclic antidepressants, systemic corticosteroids and ACE inhibitors. Following a single-blind run-in period, 249 participants who had maintained a baseline awake cough frequency ≥25 coughs/h were randomized 1:1:1:1 to the three active treatment arms of BLU-5937 (12.5, 50 and 200 mg BID) or placebo for 4 weeks of double-blind treatment. RESULTS: Ninety-four percent of patients enrolled in SOOTHE had seen at least one specialist prior to the study. Pulmonologists were the specialists most often consulted, with 78% of participants having seen at least one. Moreover, 59% had consulted with an ENT specialist, 50% with an allergist or immunologist and 46% with a gastroenterologist. A speech language pathologist had been seen by 16% of participants. Patients enrolled in the main population of SOOTHE had received an average of 5.2 ±3.1 treatments related to their cough prior to the start of the trial. Interestingly, 31% were diagnosed with asthma but 73% had received at least one prior treatment for the condition; 46% were diagnosed with GERD but 77% had received at least one prior treatment; 26% were diagnosed with UACS but 70% had received at least one prior treatment. Overall, the most common prior medications included acid reducers (76%), inhaled bronchodilators (56%) and oral antihistamines (51%). CONCLUSIONS: Overall, the broad range of specialists seen by RCC patients reflect the evaluation needed to establish the diagnosis. CLINICAL IMPLICATIONS: The large number of specialists consulted, and treatments attempted demonstrate the burden put on patients and healthcare systems by RCC. DISCLOSURES: Consultant relationship with Bellus Please note: 3/19-current Added 03/25/2022 by Michael Blaiss, value=Honoraria Speaker/Speaker's Bureau relationship with Merck Please note: 3/19-current Added 03/25/2022 by Michael Blaiss, value=Honoraria no disclosure submitted for Catherine Bonuccelli; Consultant relationship with Merck Please note: 2017-2021 by Peter Dicpinigaitis, value=Consulting fee Consultant relationship with Bayer Please note: 2019-2021 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting fee Consultant relationship with Bellus Please note: 2019-2022 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting fee Consultant relationship with Bellus Please note: 2019-2022 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting fee Removed 03/25/2022 by Peter Dicpinigaitis Consultant relationship with Shionogi Please note: 2019-2022 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting fee Consultant relationship with Chiesi Please note: 2020-2022 Added 03/25/2022 by Peter Dicpinigaitis, value=Consulting fee Employee No relevant relationships by Vivek Iyer Employee relationship with Bellus Health Please note: 2020-2022 Added 03/16/2022 by Sylvain Lanouette, value=Salary Consultant relationship with Bellus Health Please note: 2020-2022 Added 03/26/2022 by Lorcan McGarvey, value=Consulting fee Scientific Medical Advisor relationship with Merck Please note: $1001 - $5000 by Jaclyn Smith, value=Consulting fee Scientific Medical Advisor relationship with Vitalograph Ltd Please note: $5001 - $20000 by Jaclyn Smith, value=Grant/Research Support Grant Funding relationship with Merck Please note: 2020-2022 by Jaclyn Smith, value=Grant/Research Support Consultant Employee

EFFICACY AND SAFETY OF NIPOCALIMAB, AN FCRN BLOCKER, IN WARM AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA): ENERGY PHASE 2/3 STUDY DESIGN

Warm autoimmune hemolytic anemia (wAIHA) is characterized by the destruction of red blood cells (RBCs) by pathogenic autoantibodies which bind to RBCs and lead to their clearance in the spleen and liver. Patients with wAIHA can experience acute worsening of anemia, which can be a medical emergency, and have an increased risk of thromboembolic events and premature death. Nipocalimab is a fully human, aglycosylated, effectorless IgG1 monoclonal antibody that blocks the IgG binding site on the neonatal Fc receptor (FcRn) with high affinity. FcRn, which is expressed in endothelial cells, is responsible for recycling IgG into the circulation and for the relatively long half-life of IgG antibodies compared to other Igs. It is expected that nipocalimab, by blocking IgG binding to FcRn, will prevent IgG recycling and lower pathogenic IgG autoantibodies that cause many autoantibody diseases, including wAIHA. Nipocalimab has been studied in multiple phase 1 studies in healthy subjects and in a completed phase 2 study in subjects with Generalized Myasthenia Gravis (gMG). Treatment with nipocalimab was associated with rapid and durable total serum IgG and pathogenic IgG autoantibody reduction and meaningful clinical response. Here we share the rationale and study design for an adaptive, phase 2/3 multicenter, randomized, double-blind, placebo-controlled study in patients with wAIHA whose aim is to evaluate the efficacy, safety, tolerability, PK, and PD of nipocalimab compared with placebo (NCT04119050). Male or female subjects ≥18 years of age who have been diagnosed with primary or secondary wAIHA and have not experienced a sufficient response or have not tolerated currently available treatments will be included in the study. Subjects with cold antibody AIHA, cold agglutinin syndrome, mixed type (i.e., warm and cold) AIHA, or paroxysmal cold hemoglobinuria will be excluded. Participants will be randomized 1:1:1 to receive nipocalimab at two different dose schedules or placebo. Following completion of 24 weeks of double-blind treatment, participants may enter an open-label extension period to receive nipocalimab. The primary endpoint is percentage of participants achieving durable response of improvement in hemoglobin (Hgb). The main secondary endpoints are change from baseline in the total score from the FACIT-Fatigue Scale, number of participants who attain normal lactate dehydrogenase, normal haptoglobin, and normal indirect bilirubin levels at a minimum of 3 consecutive visits after baseline. ENERGY is a phase 2/3 study that will evaluate the efficacy and safety of nipocalimab in wAIHA. ENERGY is currently enrolling globally. IM received research support from Alexion, Annexon, Incyte, Kezar, Momenta, Rigel, and Sanofi; and served as a consultant for Apellis, Janssen, Momenta, Novartis, Rigel, and Sanofi. BF is a consultant of Alexion, Amgen, Janssen, Momenta, and Novartis. DC is an employee of Janssen Global Services, LLC, which is a wholly owned subsidiary of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson; was an employee of Momenta. AMBP is an employee of Janssen Latin America, which is a wholly owned subsidiary of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson. MHJ was an employee of Momenta.

A Multicenter, Randomized, Double-blind, Active-controlled, Factorial Design, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of Pitavastatin and Ezetimibe Versus Monotherapy of Pitavastatin in Patients With Primary Hypercholesterolemia

Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia. Korean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups. Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy. gov identifier: NCT04584736.

34587 Efficacy of ruxolitinib cream for the treatment of atopic dermatitis by anatomic region: Pooled analysis from two randomized phase 3 studies

Atopic dermatitis (AD) is a highly pruritic inflammatory skin disease. Two phase 3 studies (TRuE-AD1/TRuE-AD2) enrolled patients aged ≥12 years with AD for ≥2 years, an Investigator’s Global Assessment (IGA) score of 2/3, and 3%–20% affected body surface area. Patients (total N = 1249; median age, 32 years) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream, 1.5% ruxolitinib cream, or vehicle cream for 8 weeks of double-blind treatment, and thereafter continued in a long-term, 44-week period of the studies.