Open-label Study Research Articles

A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy.

Islatravir is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV-1. People living with HIV-1 receiving methadone maintenance therapy may benefit from islatravir. This study was designed to evaluate single-dose islatravir on steady-state methadone pharmacokinetics. A nonrandomized, open-label study (NCT04568603) was conducted and included adult participants receiving methadone therapy. Participants received their standard methadone therapy and a single oral dose of islatravir 60mg concomitantly. Blood samples were collected to determine methadone and islatravir pharmacokinetics. Fourteen participants aged 26-63years were enrolled; 13 completed the study. The geometric mean ratios for methadone area under the concentration-time curve from time 0 to 24hours (AUC0-24), maximum plasma concentration (Cmax), and concentration at 24hours (C24) were 1.03, 1.01, and 1.07, respectively. Similar effects were seen for the R- and S-enantiomer of methadone (R-methadone: AUC0-24, 1.03; Cmax, 1.02; and C24, 1.06; S-methadone: AUC0-24, 1.03; Cmax, 1.01; and C24, 1.08). For islatravir, based on a comparison with historical data, the geometric mean ratios for AUC0-inf and Cmax were 1.18 and 0.86, respectively. Coadministration of a single dose of islatravir and methadone was generally well tolerated. Single-dose islatravir did not affect steady-state methadone pharmacokinetics in a clinically meaningful way.

EVALUATION OF EFFICACY AND SAFETY OF AZITHROMYCIN AND DOXYCYCLINE IN TREATMENT OF ACNE VULGARIS WITH DIFFERENT LEVELS OF SERUM TESTOSTERONE: A PROSPECTIVE, RANDOMIZED, CONTROLLED, COST-EFFECTIVE, COMPARATIVE STUDY

Objectives: The objectives of this study are to compare the therapeutic efficacy, safety, quality of life (QoL), and cost-effectiveness of azithromycin and doxycycline in patients with acne vulgaris and the correlation of serum testosterone levels with the severity of acne. Methods: A prospective, randomized, open-label study was conducted at a tertiary care hospital in South India, according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice principles. After institutional ethics committee approval, 100 patients aged 15–40 with moderate-to-severe acne were enrolled, excluding those with a history of gastritis, drug hypersensitivity, pregnancy, or under 12 years old. Participants were randomized to receive either oral azithromycin 500 mg daily for three consecutive days each week for 4 weeks, or doxycycline 100 mg daily for 28 days, along with topical treatments. Efficacy was measured by the type and number of acne lesions, graded according to standardized criteria. QoL was assessed using the Cardiff Acne Disability Index (CADI). Serum testosterone levels were correlated with acne severity. Results: Of the 96 patients (42 males, 54 females) who completed the study, 49 were in the azithromycin group and 47 in the doxycycline group. The mean age was 23.5 years in the azithromycin group and 22.1 years in the doxycycline group. Significant reductions in acne severity and number of lesions were observed in both groups (p<0.0001), with azithromycin showing superior improvement (p<0.01). At baseline, most patients had Grade 3 or 4 acne, which improved significantly post-treatment. QoL improvements were also significant in both groups, with mean CADI scores reducing from around 8 to below 4 (p<0.0001). A weak positive correlation (r=0.24) was found between serum testosterone levels and acne severity. Adverse events were mild and did not necessitate discontinuation. To achieve a 1 unit decrease in CADI, azithromycin treatment costed an additional rupees of 264.5 over doxycycline. Conclusion: Azithromycin and doxycycline are effective treatments for moderate-to-severe acne vulgaris, with significant improvements in clinical and QoL outcomes. While azithromycin offers better clinical efficacy, doxycycline provides a more cost-effective option. Further studies could explore long-term outcomes and the impact of hormonal variations on treatment efficacy.

Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management in people with hemophilia A or B.

Fitusiran is an investigational small interfering RNA therapeutic that targets antithrombin (AT) to rebalance hemostasis in people with hemophilia. Here we present the results of the completed Phase 2 open-label extension study, which evaluated the long-term safety and efficacy of fitusiran in participants with moderate or severe hemophilia A or B, with or without inhibitors. Male participants who had completed the Phase 1 study (NCT02035605) were enrolled. Participants received monthly subcutaneous fitusiran (50 mg or 80 mg) under the original dose regimen until a voluntary dosing pause in 2020, following which the AT-based dose regimen was introduced, targeting the recommended AT activity levels of 15-35%. Thirty-four participants (hemophilia A [n=27]; hemophilia B [n=7]) were enrolled in the Phase 2 study and treated with fitusiran for a median exposure of 4.1 years. Adverse events reported on the original and the AT-based dose regimen were consistent with the identified risks of fitusiran. Following implementation of the AT-based dose regimen, no thrombotic events, and a reduction in the incidence of elevated transaminases and biliary events were reported. The observed median annualized bleeding rate (ABR) on the AT-based dose regimen (0.87) was comparable to the ABR under the original dose regimen (0.70). Furthermore, fitusiran prophylaxis was associated with improved health-related quality of life compared to baseline and provided successful hemostatic control during surgical procedures and invasive interventions. Overall, fitusiran was well tolerated and effective bleeding control was maintained on an AT-based dose regimen. This trial was registered at www.clinicaltrials.gov as #NCT02554773.

Efficacy of vitamin/mineral supplement on children with Down syndrome and autism spectrum disorder

Objectives The management of language deficits and therapeutic efficacy of micronutrients supplementation in improving presentations in Down syndrome (DS) and autistic children are very challenging. The aim of this open-label study is to explore the effect of micronutrients supplementation together with language stimulating environment on language abilities, the severity of autism spectrum spectrum (ASD) presentations, and on serum levels of some micronutrients and serotonin in these children. Methods DS and autistic children (N = 57) who presented with intellectual disability and developmental language delay were subjected to assessment of the language abilities, severity of autism in ASD participants, in addition to measuring of serum levels of iron, magnesium, B6, B12, and serotonin level by ELISA before and after 16 wk of an oral once-per-day dietary supplementation, together with a home-based language stimulation. The supplement included vitamins (B complex, E, C), trace minerals (Iron, magnesium, zinc), and other nutrients. Results All the participants showed improved language abilities (p = 0.01). Autistic children showed reduced autism severity (p = 0.005). Increased levels of iron, magnesium, vitamin B6, and serotonin in the serum after supplementation have been observed (p ≤ 0.05). Conclusions This research provides further support for the benefits of dietary supplementation with home-based language stimulation for DS and autistic children.

An open label, single arm, pilot study to evaluate the safety, tolerability, and efficacy of daily fluconazole 150 mg in subjects suffering from Tinea cruris and Tinea corporis

Background Dermatophytes are the most common superficial fungal infections worldwide and are treated with prescribed regimens of terbinafine and itraconazole, or with weekly doses of fluconazole. Dermatologists are increasingly encountering treatment failures, and experts suggest that standard treatment regimens are not applicable anymore. We planned an open-label study to evaluate the results of fluconazole 150 mg daily for 8 weeks in patients with tinea cruris and tinea corporis. Methods Patients were enrolled from the La’Mer Clinic, Mumbai, India. We included adult subjects with uncomplicated dermatophytosis confirmed by microscopic examination of skin scrapings. Pregnancy, poor renal function, and recent exposure to anti-fungal therapy were exclusion criteria. Patients were reviewed on days 14, 28 and 56. The treating doctor scored the severity of erythema, scaling, and pruritus on a four-point scale: absent, mild, moderate, and severe. Of 107 subjects screened, 100 were finally included in the study. Eleven were lost to follow up and one subject withdrew consent. Results The site of disease was body alone in 29, groin alone in 7, and both body and groin in 64 cases. At 5 weeks, 98%, 100%, and 97% of patients had no scaling, erythema, and pruritus, respectively. Skin scrapings showed 100% mycological cure. In one patient the alanine transaminase level rose from 54.9 to 100.2 U/L, and qualified as a grade 1 adverse event not requiring intervention. No other significant adverse events were noted. Conclusions Our results suggest that fluconazole 150 mg daily for eight weeks effectively treats dermatophytosis. This regimen is safe and well-tolerated even in patients with co-morbidities. Fluconazole is about eight times less expensive than itraconazole or terbinafine and may be the preferred therapy. Registration The trial was registered with Clinical Trials Registry, India (Registration number CTRI/2020/06/026110) on 24 June 2020. FDC Company, India, provided financial support for the study.

First results of migoprotafib, a potent and highly selective Src homology-2 domain-containing phosphatase 2 (SHP2) inhibitor in patients with advanced solid tumors.

Src homology-2 domain-containing phosphatase 2 (SHP2) promotes RAS-MAPK signaling and tumorigenesis and is a promising therapeutic target for multiple solid tumors. Migoprotafib is a potent and highly selective SHP2 inhibitor designed for the treatment of RAS-MAPK driven cancers, particularly in combination with other targeted agents. Here we report first-in-human study results of single agent migoprotafib in advanced solid tumor patients. We conducted a phase 1a, open-label, multi-center, dose-escalation and expansion study in adult patients with locally advanced or metastatic solid tumors. The key objectives were to evaluate safety, pharmacokinetics, pharmacodynamics (peripheral blood pERK) and preliminary anti-tumor activity. Fifty-six heavily pre-treated patients were treated with migoprotafib (10-150 mg QD). Migoprotafib had a rapid absorption rate (~0.5-2 hours) with dose-dependent increases in exposure and pathway modulation (pERK changes). The maximum tolerated dose was 100 mg and the recommended phase 2 dose (RP2D) was 60 mg daily (QD) based on safety, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity. Migoprotafib was generally well tolerated with the most frequent adverse events of diarrhea, peripheral edema, dyspnea, anemia, constipation, fatigue, AST increase and platelet count decrease. Stable disease was observed in 10 patients (18%). Migoprotafib had predictable, dose-dependent PK with an effective half-life that supports QD dosing and demonstrated promising safety, tolerability, and clinical activity at the RP2D. Further clinical testing of migoprotafib in combination with other targeted agents is warranted.

Budesonide/formoterol turbuhaler vs pMDI salbutamol for acute asthma in outpatient emergency department: a prospective, randomized, open-label study

Background The Global Initiative for Asthma (GINA) has suggested the need for more studies on inhaled corticosteroid (ICS)-formoterol in the Emergency Department (ED). Objectives We aimed to compare the outcomes of budesonide/formoterol (160/4.5 mcg/inhalation) turbuhaler versus pressurized metered-dose inhaler (pMDI) salbutamol (100 mcg/puff) in acute asthma in the outpatient ED. Methods This single-centre, prospective, randomized, and open-label study involved adult asthma patients with mild to moderate asthma exacerbation who attended the outpatient ED of a tertiary hospital in Malaysia. The intervention arm received budesonide/formoterol (Symbicort® 160/4.5 mcg) turbuhaler, while the control arm received pMDI salbutamol with a valved holding chamber. Stratified randomization with variable baseline ICS use was employed. Direct discharge rate from outpatient ED was the primary outcome. Vital signs pre- and post-treatment between the two arms were also compared. Results Seventy-four (n = 37 for each arm) asthma patients were recruited. Baseline clinical characteristics were comparable between the two arms. Direct discharge rates from ED were comparable between the intervention (94.6%) and the control (91.9%) arms (p = 1.000). Post-treatment outcomes (respiratory rate, oxygen saturation, peak expiratory flow rate) were similar between the two arms, except for the higher increment of heart rate (p < 0.001) and lesser reduction of blood pressure in the control arm (p = 0.013). Intravenous hydrocortisone use was significantly higher in the control arm (n = 19, 51.4%) than in the budesonide/formoterol arm (n = 6, 16.2%) (p = 0.001). Conclusion Budesonide/formoterol turbuhaler is as effective as pMDI salbutamol in treating asthma exacerbation in the outpatient ED with less effect on heart rate and lower usage of intravenous corticosteroids.

Evaluation of NUN-004, a Novel Engineered Ephrin Antagonist, in Healthy Volunteers and Patients with Amyotrophic Lateral Sclerosis: A Phase I/Ib, Open-Label, Escalating Dose and Extended Access Study.

Erythropoietin-producing hepatocellular carcinoma A4 (EphA4) is implicated in the pathophysiology of amyotrophic lateral sclerosis. EphA4 fusion protein (EphA4-Fc) inhibits EphA4 function in vivo but is too short-lived for prolonged therapy. NUN-004 (mEphA4-Fc) is a modified EphA4-Fc engineered for an extended half-life. This first-in-human phase I/Ib study evaluated the safety, tolerability, pharmacokinetics, immunogenicity and efficacy of NUN-004 in healthy volunteers and patients with amyotrophic lateral sclerosis. In this open-label study, Part 1 enrolled 20 healthy volunteers in five single ascending dose cohorts (1, 3, 10, 20 and 30 mg/kg), followed by Part 2, which enrolled eight patients with amyotrophic lateral sclerosis in two multiple ascending dose cohorts (cycle 1: 15 and 30 mg/kg) who could continue into an extended access phase (cycles 2-6: 15 mg/kg) for a total of 6 months' treatment. All participants received intravenous NUN-004; multiple dosing was administered weekly in 28-day cycles. Primary endpoints included safety assessments, single-dose and multiple-dose pharmacokinetics, and anti-drug antibodies. Efficacy assessments were Amyotrophic Lateral Sclerosis Function Rating Score Revised (ALSFRS-R) and forced vital capacity. NUN-004 was well tolerated, with no serious adverse events or discontinuations. NUN-004 exposure generally increased with dose. Single-dose half-life was 111.7 (± 22.8) h in healthy volunteers (n = 20) and 74.4 (± 19.4) h in patients (n = 6). Steady state was observed in patients by day 8. Steady-state half-life (cycle 1 doses 2-4) was 83.7 (± 26.6) to 101.1 (± 46.0) h. No antibody response was observed. ALSFRS-R showed a slight improvement (+0.09 points/month) to cycle 4 and a slight decline (-0.35 points/month) over the whole study. Forced vital capacity trends were consistent with ALSFRS-R. This study supports the safety, tolerability and extended half-life of NUN-004, and provides preliminary evidence for its ability to ameliorate disease progression in an amyotrophic lateral sclerosis cohort. Registered on ANZCTR under identifier ACTRN12621000514808 (3 May, 2021).

Apomorphine for prolonged disorders of consciousness: a multimodal open-label study

Apomorphine is a dopaminergic candidate therapy to improve recovery in patients with prolonged disorders of consciousness (PDoC). Behavioural improvements were previously described in non-controlled case series, but its efficacy and neural mechanisms remain largely unknown. This open-label controlled study using multimodal outcome measures investigates the action of apomorphine in severely brain-injured patients. Thirteen PDoC patients received 30-day subcutaneous apomorphine treatment (n=6) or standard care (control group, n=7) in a neurological rehabilitation centre between February 2018 and January 2021. The apomorphine group was monitored 30 days before treatment initiation, during treatment and one year after treatment. Primary outcome measure was defined as changes in behavioural diagnosis using the Coma Recovery Scale-Revised (CRS-R). CRS-R index, recovery of new conscious behaviours, DoC-feeling scores, high-density electroencephalography, and fluorodeoxyglucose positron emission tomography were employed as secondary outcome measures. The control group was monitored with repeated CRS-R only. Registration: EudraCT 2018-003144-23; Clinicaltrials.govNCT03623828. Groups (apomorphine vs. control: odds ratio 8.9, 95% CI 3.3-17.8) and study phase (treatment vs. baseline, apomorphine group only: odds ratio 3.9, 95% CI 1.5-10.1) significantly influenced positive changes in behavioural diagnosis. At one-year post-injury, 4/6 patients in the apomorphine group and 1/7 patients in the control group had improved their diagnosis. Similarly, CRS-R index was significantly influenced by study phase (treatment vs. baseline). All items on the DoC-feeling score were rated higher after treatment than before by both family and medical staff. Patients in the apomorphine group recovered more conscious behaviours than control patients. Alpha-band whole-brain connectivity and participation coefficient, as well as alpha-band parieto-temporal connectivity and frontal participation coefficient were higher after treatment than at baseline. Whole-brain metabolism increased by a relative mean of 13.8% after treatment compared to baseline, with a significant effect of timing (pre-vs. post-treatment scans) on regional SUV. Long-lasting consciousness improvements were observed in patients treated with apomorphine, compared to controls and compared to baseline. Changes in brain connectivity and metabolism were observed after treatment, providing insights into possible neurophysiological mechanisms and target areas. This open-label study confirmed the feasibility and safety of apomorphine treatment, which may represent a key therapeutic option for PDoC. University and University Hospital of Liege, Belgian National Funds for Scientific Research, Fund Generet of the King Baudouin Foundation, AstraZeneca Foundation, Leon Fredericq Foundation and NeuroHealing Pharmaceuticals Inc.

S19 Real-World Efficacy and Safety of Ozanimod in US Patients With Moderately to Severely Active Ulcerative Colitis: Initial Results from POLARIS, an Ongoing Phase 4 Open-Label Study

S19 Real-World Efficacy and Safety of Ozanimod in US Patients With Moderately to Severely Active Ulcerative Colitis: Initial Results from POLARIS, an Ongoing Phase 4 Open-Label Study

Cortical hypometabolism as a predictor of intermittent theta burst stimulation response in treatment-resistant depression patients: An open-label study

Cortical hypometabolism as a predictor of intermittent theta burst stimulation response in treatment-resistant depression patients: An open-label study

Does Vitamin E Supplementation Alter Hormonal Levels in Polycystic Ovary Syndrome: A Systematic Review of Randomized Controlled Trials

Background: Vitamin E influences hormonal parameters in women, but the evidence concerning its effectiveness in polycystic ovarian syndrome (PCOS) are constrained. Objective: The objective of this systematic review is to perceive the mechanism behind the hormonal effects of vitamin E in PCOS and explore the effectiveness of vitamin E by analyzing the clinical studies. Methods: Electronic bibliographic databases, such as PubMed, Scopus, ProQuest, DOAJ, ScienceDirect, and Cochrane Library, were searched for clinical studies scrutinizing the effect of vitamin E supplementation on PCOS. The systematic review protocol is registered in PROSPERO (CRD42021272963) and was performed as per the PRISMA guidelines. Records analyzing the hormonal parameters were included. For individual study, the risk of bias was ascertained with NHLBI protocol for controlled randomized studies. Results: There were 1438 records identified, of which seven records were retrieved which met the inclusion criteria. Bibliographic details, number of participants, the dose of vitamin E, duration of the treatment and trial, parameters analyzed, and outcome of each study were extracted comprehensively. In the review, the majority of the studies embraced high-quality studies, which included double-blinded controlled trials, open-label controlled studies, and cohort studies. Conclusion: Vitamin E implies having a progesterone-like impression with estrogenic and androgenic properties. Furthermore, the ability of vitamin E as an antioxidant is also advantageous in PCOS women. However, there is a lack of empirical evidence on its mechanism, and the inadequacy of large-scale concerns about different age groups against PCOS is requisite.

S9 Efficacy and Safety of Obefazimod in Patients With Ulcerative Colitis at Week 48 of an Open-Label Maintenance Study Among Clinical Nonresponses at Week 8 of the Phase 2b Induction Trial

S9 Efficacy and Safety of Obefazimod in Patients With Ulcerative Colitis at Week 48 of an Open-Label Maintenance Study Among Clinical Nonresponses at Week 8 of the Phase 2b Induction Trial

Open-Label Study of the Efficacy, Safety, and Durability of Peanut Sublingual Immunotherapy in Peanut-Allergic Children.

Open-Label Study of the Efficacy, Safety, and Durability of Peanut Sublingual Immunotherapy in Peanut-Allergic Children.

Management of obesity with semaglutide or metformin in patients with antipsychotic-induced weight gain (MOSA): a non-randomised open-label pilot study

BackgroundAntipsychotic-induced weight gain (AIWG) represents a significant clinical challenge for both patients and clinicians, requiring appropriate interventions to prevent or reverse weight gain in patients using antipsychotics. Glucagon-like peptide 1 (GLP-1) agonists represent a novel approach to the management of obesity that has recently attracted considerable attention. Semaglutide (a GLP-1 agonist) has been demonstrated to result in notable weight loss. The present study investigates whether semaglutide is equally effective in achieving weight loss in patients with AIWG.MethodsA prospective, non-randomised cohort study was conducted with the objective of evaluating the efficacy and safety of oral semaglutide for the treatment of AIWG in routine outpatient clinical practice. Subsequently, the results were compared with those of a control group of AIWG patients taking metformin.ResultsAfter 16 weeks, the mean body weight loss was 4.5 kg (95% confidence interval (CI), -6.7 to -2.3 kg; p < 0.001) in the semaglutide group (n = 10) versus 2.9 kg (95% CI, -4.5 to -1.4 kg; p < 0.001) in the metformin group (n = 26). This corresponds to an average body weight loss of 4% for semaglutide, and 2.5% for metformin. The respective reductions in body mass index (BMI) and waist circumference were -1.7 kg/m2 (95% CI, -2.4 to -1.0 kg/m2; p < 0.001) and -6.8 cm (95% CI, -9.7 to -3.8 cm; p < 0.001) for semaglutide. The observed reductions for metformin were -0.8 kg/m2 (95% CI, -1.4 to -0.3 kg/m2; p = 0.001) and -3.4 cm (95% CI, -5.4 to -1.3 cm; p = 0.001). The differences between the two groups were not statistically significant. In both groups, adverse effects were typically mild and transient, predominantly nausea. Furthermore, psychiatric symptoms were reduced, and quality of life improved.ConclusionsOral semaglutide represents a viable, effective, and safe treatment option for psychiatric patients. However, further investigation is required to corroborate these findings.

Efficacy of Rifaximin and Probiotics in the Treatment of Small Intestinal Bacterial Overgrowth When Used Concomitantly or Sequentially

Background: With the prevalence of small intestinal bacterial overgrowth (SIBO) on the rise, treatment has become of paramount importance for patients suffering from this disease. Antibiotics used to treat SIBO include rifaximin, ciprofloxacin, metronidazole, and neomycin. Probiotics reinforce the small intestine's internal microbiota and help cure many diseases. Aim: In this study, we aimed to evaluate the efficacy of rifaximin together with a multi-strain probiotic in patients with SIBO. In a multi-center open-labeled prospective study, recruited patients were randomized into two groups treated with rifaximin as a base and probiotics that varied in the timing of initiation (concomitantly; group A or sequentially; group B) for treating the clinical manifestations of the disease. The primary endpoint evaluated the clinical response to treatment, and the secondary endpoint evaluated the eradication rates. Results: Eradication rates revealed that 69.8% of the patients in group A and 74.8% of the patients in group B were successfully treated and returned with negative lactulose hydrogen breath test results. Clinical response rates were divided into partial and complete responders; partial responders were reported in 23.3% and 26.6% of patients in groups A and B, respectively, and complete responders were reported in 62.7% and 59.5% of patients in groups A and B, respectively. Overall, partial or complete responders' combined rate comprised 86% and 86.2% in groups A and B, respectively. There were no reported side effects by patients treated with rifaximin and the multi-strain probiotic for both protocols. Conclusion: The addition of probiotics, both concomitantly or sequentially, to the treatment regimen acts synergistically with rifaximin to improve outcomes. According to our study, there were no statistical differences between the two regimens. In conclusion, the extension of probiotics in the sequential regimen provided a more prolonged clinical response rate.

An Evaluation of VYC-17.5L for the Treatment of Marionette Lines: A Prospective, Open-Label, Postmarketing Study.

Marionette lines are a feature of the aging face, descending from the oral commissures towards the jaw. VYC-17.5 L is a dermal filler that contains 17.5 mg/mL of hyaluronic acid (HA) and lidocaine (3 mg/mL); it is intended for the treatment of skin depressions. VYC-17.5 L has been shown to be safe and effective in different conditions, but there is a lack of published literature on its effectiveness in marionette lines. This 12-month prospective, open-label, post-marketing study evaluated the effectiveness and safety of the injectable HA filler VYC-17.5 L for the improvement of marionette lines. Adults (≥ 18 years) with mild-to-severe marionette lines on the validated Allergan Marionette Line Scale (AMLS) received VYC-17.5 L on Day 1 with optional touch-up on Day 14. The primary endpoint was proportion of participants with ≥ 1-point change in AMLS from baseline at Month 1 (M1). Secondary endpoints were investigator- and participant-rated Global Aesthetic Improvement Scale (GAIS), FACE-Q satisfaction with facial appearance, and appraisal of lines: marionette. Safety was assessed throughout. A total of 83 participants completed the study; 69.9% of participants had ≥ 1-point change in AMLS at M1. Investigator and participant GAIS showed improvement. Both FACE-Q scores significantly improved from baseline (p < 0.0001). A significant volume improvement was seen and maximized at M1. Most participant-reported injection site reactions were mild or moderate and resolved within 8 days; 14 subjects reported adverse device effects, with the most common being pain, which resolved within 8 days. This prospective, open-label study showed that VYC-17.5 L effectively improved marionette lines and was well tolerated.

Cannabis combined with oxycodone for pain relief in fibromyalgia pain: a randomized clinical self-titration trial with focus on adverse events.

We determined whether adding cannabis to oxycodone for chronic non-cancer pain management could reduce treatment-related adverse effects (AEs) while maintaining effective analgesia. In this open-label study, fibromyalgia patients aged ≥18 years were randomized to receive 5 mg oxycodone tablets (max. four times/day), 150 mg of inhaled cannabis containing 6.3% Δ9-tetrahydrocannabinol and 8% cannabidiol (max. times inhalation sessions/day), or a combination of both for 6 weeks. The primary endpoint was treatment-related adverse events, assessed using a 10-point composite adverse event (cAE) score; additionally, we recorded daily reported pain relief and daily tablet and cannabis consumption. In total, 23 patients were treated with oxycodone, 29 with cannabis, and 29 with the oxycodone/cannabis combination. Three patients from the oxycodone group (13%) and 18 patients from the cannabis groups (31%, 9 in each group) withdrew from the trial within 2-3 weeks because of the severity of AEs. There were no differences in treatment-related cAE scores among the three groups that completed the study (p = 0.70). The analgesic responder rate showed a ≥1- point reduction in pain in 50% and a ≥2-point reduction in 20% of patients, while 50% of patients experienced no treatment benefit. The combination treatment reduced oxycodone tablet consumption by 35% (p = 0.02), but it did not affect the number of cannabis inhalation sessions. Cannabis combined with oxycodone offered no advantage over either treatment alone, except for a reduction in opioid tablet intake; however, the overall drug load was the highest in the combination group. Moreover, cannabis was poorly tolerated and led to treatment discontinuation in one-third of participants treated with cannabis. The trial was registered at the WHO International Clinical Trials Registry Platform (trialsearch.who.int) on July 26, 2019, identifier NL7902.

Efficacy and safety of Neurocognitive Adaptive Training for Depression combined with SSRIs for treating cognitive impairment among patients with late-life depression: a 12-week, randomized controlled study

BackgroundThis randomized, open-label study examined the therapeutic effects of Neurocognitive Adaptive Training for Depression (NCAT-D) combined with selective serotonin reuptake inhibitors (SSRIs) on cognitive impairment among patients with late-life depression (LLD).MethodStudy data were collected from May 5, 2021, to April 21, 2023. Outpatients who met the diagnostic criteria for major depressive disorder according to the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (i.e., a total score on the 17-item Hamilton Depression Rating Scale (HAMD-17) ≥ 18 and a total score on the Montreal Cognitive Assessment scale (MOCA) < 26) were recruited at Beijing Anding Hospital. These participants were randomly assigned to receive up to 12 weeks of NCAT-D and SSRIs treatment (n = 57) or SSRIs with a control treatment (n = 61). Primary outcomes included changes in Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores from baseline to week 12 between the two groups. Assessments were conducted at baseline, after 2 weeks, 4 weeks, 8 weeks, and at 12 weeks. Mixed model repeated measures (MMRM) analysis was performed on modified intention-to-treat (mITT) and completer populations.ResultsThe full analysis set (FAS) included 118 patients (NCAT-D and SSRIs group, n = 57; SSRIs and Control group, n = 61). During the 12-week study period, MMRM analysis revealed a significantly greater reduction in cognitive function (as indicated by ADAS-cog total scores) from baseline to post-treatment in the NCAT-D and SSRIs group compared to the SSRIs and Control groups [(F (1,115) = 13.65, least-squares mean difference [95% CI]: −2.77 [− 3.73, − 1.81], p < 0.001)]. The intervention group showed a significantly greater reduction in HAMD-17 scores compared to the control group [MMRM, estimated mean difference (SE) between groups: −3.59 [− 5.02, − 2.15], p < 0.001]. There was no significant difference in the incidence of adverse events between the two groups.ConclusionsNCAT-D combined with SSRIs was efficacious and well tolerated in LLD patients with cognitive impairment.Trial registrationRegistered on October 18, 2022, at ClinicalTrials.gov Identifier: (#NCT05588102).

The pharmacokinetics of brensocatib in participants with renal impairment following a single oral administration.

Brensocatib is an oral, selective, competitive and reversible dipeptidyl peptidase 1 inhibitor in development for the treatment of bronchiectasis. This study evaluated the pharmacokinetics (PKs), safety and tolerability of brensocatib in participants with varying degrees of renal impairment and normal renal function. In this phase 1, multicentre, open-label study, 28 participants with mild, moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] 60 to <90, 30 to <60 and 15 to <30 mL/min/1.73 m2, respectively) or normal renal function (≥90 mL/min/1.73 m2) received a single oral 25-mg dose of brensocatib. Blood samples were collected to measure brensocatib PKs at predetermined time points over the 14-day study period. PK parameters were derived using noncompartmental methods. Demographic and baseline characteristics were similar across groups. There were no significant differences between groups in brensocatib PK parameters. The mean coefficient of variation (CV) of elimination half-life of brensocatib was 37.0 (15.3), 42.8 (21.7), 36.3 (22.9) and 39.1 (17.8) h for mild, moderate, severe and normal renal function groups, respectively. Single-dose brensocatib was quickly absorbed; all groups had a median time to maximum observed plasma concentration of 1h. Regression model analyses indicated no significant relationships between selected brensocatib PK parameters and eGFR. No treatment-emergent adverse events were reported during the study. Single-dose brensocatib was well tolerated. The study data do not indicate a significant effect of renal impairment on brensocatib elimination and systemic exposure, suggesting that dose adjustment of brensocatib is not necessary in participants with renal impairment. NCT05673603.