Active-controlled Study Research Articles

Comparison of efficacy of diclofenac and tramadol in relieving pain in patients of acute pancreatitis: A randomized parallel group double blind active controlled pilot study.

Opioids and non steroidal anti inflammatory drugs (NSAIDs) are commonly used for pain relief in acute pancreatitis (AP). Opioids carry risk of sphincter of oddi constriction. Although diclofenac prevents post endoscopic retrograde cholangio-pancreatography (ERCP) pancreatitis, few reports of diclofenac associated AP are also present. Although, both tramadol and diclofenac are commonly used for pain relief in AP, no study has evaluated their comparative efficacy and safety. Forty-six eligible participants were randomized to either diclofenac or tramadol. Primary objectives ofour study were improvement in pain intensity onvisual analogue scale (VAS pain score after 1hr of drug administration)and number of patients requiring supplementary analgesia. The secondary objectives were total number of times of supplementary analgesia requirement, time to significant decrease (33%) in VAS pain score from baseline, number of painful days (VAS pain score>5), VAS pain score on 7th day, side effects, all cause death and complications of pancreatitis between the two groups. Although 46 patients were randomized, the final analysis included 41 participants. Five patients were withdrawn from the study (intubation=3, altered sensorium=2). No significant difference was seen in terms of VAS score after 1hr of drug administration, number of patients requiring supplementary analgesic and number of painful days. However, time taken to significant reduction of pain was lower in the diclofenac group (p=.028). Both the agents were comparable in terms of safety. Although complications were less in the diclofenac group, the difference was not statistically significant. Both diclofenac and tramadol are equally effective in controlling pain in AP with similar safety profile. There are no studies that have compared the safety and efficacy of two commonly used analgesics for pain relief in patients with AP. We found that both diclofenac and tramadol are equally effective in decreasing the pain associated with AP. There is also no significant difference in the incidence of side effects between both the groups. Hence both diclofenac and tramadol can be used safely and effectively for pain control in AP. The trial was registered with clinical trials registry India (Number- CTRI/2018/05/014309).

Improved glycaemic variability and time in range with dapagliflozin versus gliclazide modified release among adults with type 2 diabetes, evaluated by continuous glucose monitoring: A 12-week randomized controlled trial.

To evaluate whether there is a difference between the effects of dapagliflozin and gliclazide modified release (MR) on glycaemic variability (GV) and glycaemic control, as assessed by continuous glucose monitoring (CGM), in individuals with uncontrolled type 2 diabetes. This randomized, open-label, active-controlled study was conducted in individuals with uncontrolled type 2 diabetes who were drug-naïve or on steady-dose metformin monotherapy. Participants were treated once daily with 10 mg dapagliflozin or 120 mg gliclazide MR. CGM and GV index calculations were performed at baseline and after 12 weeks. In total, 97 participants (age 57.9 ± 8.7 years, 50.5% men, baseline glycated haemoglobin 63 ± 9.8 mmol/mol [7.9 ± 0.9%]) were randomized, and 94 completed the 12-week protocol. Intention-to-treat (ITT) and per-protocol (PP) analyses showed that the reduction in GV, as measured by the mean amplitude of glycaemic excursions, was superior in the dapagliflozin group versus the gliclazide MR group (-0.9 mmol/L [95% CI -1.5, -0.4] vs -0.2 mmol/L [95% CI -0.6, 0.3]; P = 0.030 [ITT]). The reductions in GV estimated by the coefficient of variation and SD were greater in the dapagliflozin group. Moreover, dapagliflozin increased the glucose time in range (TIR; 3.9-10 mmol/L) by 24.9% (95% CI 18.6, 31.2) vs. 17.4% (95% CI 11.6, 23.3) in the gliclazide MR group (P = 0.089 [ITT]; P = 0.041 [PP]). Dapagliflozin improved GV and increased TIR more efficiently than gliclazide MR in individuals with type 2 diabetes over 12 weeks, as demonstrated by CGM.

Large-Eddy Simulation of Yawed Wind-Turbine Wakes: Comparisons with Wind Tunnel Measurements and Analytical Wake Models

In this study, we validated a wind-turbine parameterisation for large-eddy simulation (LES) of yawed wind-turbine wakes. The presented parameterisation is modified from the rotational actuator disk model (ADMR), which takes account of both thrust and tangential forces induced by a wind turbine based on the blade-element theory. LES results using the yawed ADMR were validated with wind-tunnel measurements of the wakes behind a stand-alone miniature wind turbine model with different yaw angles. Comparisons were also made with the predictions of analytical wake models. In general, LES results using the yawed ADMR are in good agreement with both wind-tunnel measurements and analytical wake models regarding wake deflections and spanwise profiles of the mean velocity deficit and the turbulence intensity. Moreover, the power output of the yawed wind turbine is directly computed from the tangential forces resolved by the yawed ADMR, in contrast with the indirect power estimation used in the standard actuator disk model. We found significant improvement in the power prediction from LES using the yawed ADMR over the simulations using the standard actuator disk without rotation, suggesting a good potential of the yawed ADMR to be applied in LES studies of active yaw control in wind farms.

Pembrolizumab versus chemotherapy in recurrent, advanced urothelial cancer in Japanese patients: a subgroup analysis of the phase 3 KEYNOTE-045 trial

BackgroundThe open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan.Patients and methodsAnalysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points.ResultsFifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44–1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32–1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95–3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3–5 events, occurred less frequently with pembrolizumab.ConclusionsPembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab.

Randomized Phase 2 Zanubrutinib (BGB-3111) + Obinutuzumab Vs Obinutuzumab Monotherapy in Patients with Relapsed/Refractory Follicular Lymphoma (R/R FL)

Randomized Phase 2 Zanubrutinib (BGB-3111) + Obinutuzumab Vs Obinutuzumab Monotherapy in Patients with Relapsed/Refractory Follicular Lymphoma (R/R FL)

Numerical Study of Active Aerodynamic Control via Flow Discharge on a High-Camber Rear Spoiler of a Road Vehicle

In this study, a numerical investigation of the active aerodynamic control via flow discharge was performed on a two-dimensional simplified vehicle with a spoiler. The analysis was performed using computational fluid dynamics techniques based on the unsteady Reynolds averaged Navier–Stokes equations. Unlike the conventional aerodynamic control methods, in which the control flow is forcibly injected to increase the lift or reduce the drag, the flow discharge method uses the ram air flow to reduce both the downforce and aerodynamic drag of a road vehicle. The technique of aerodynamic control via the flow discharge is applied to a simplified vehicle with a rear spoiler. For the isolated spoiler, at a discharge speed of 40% of the vehicle driving speed, the flow discharge at 75% of the chord exhibited a reduction of 4.5% and 1.8% in the aerodynamic drag and downforce reduction, respectively. For the vehicle with a spoiler, the drag and downforce were respectively reduced, on average, by 3.4% and 19.3% for a vehicle velocity range of 100–300 km/h; in this case, the discharge speed was 40% of the vehicle driving speed, and the discharge position was 75% of the chord owing to the interaction between the spoiler separation flow and vehicle wake.

Efficacy and safety of neuronox® for lateral canthal lines: a phase I/III, multicenter, randomized, double-blind, active-controlled study

Introduction Neuronox® has not yet been investigated for its efficacy and safety in the treatment of lateral canthal lines (LCL). Methods This study was a randomized, double-blind, active drug controlled, multicenter, 16 week, Phase I/III study designed to determine the non-inferiority of Neuronox® compared to onabotulinumtoxin A (ONA) in the treatment of moderate to severe LCL. Thirty subjects in Phase I and 220 subjects in Phase III were randomized in a 1:1 ratio to receive a single treatment (24 U) of either Neuronox® or ONA. The primary endpoint of the Phase III study was the responder rate according to the proportion of subjects achieving Grade 0 (none) or 1 (mild) from 2 (moderate) or 3 (severe) in LCL severity at maximum smile as assessed by the investigators at Week 4. Additional efficacy endpoints and safety endpoints (adverse events) were also evaluated. Results The primary endpoint was achieved as the proportion of responders was 83% for both Neuronox® and ONA, thus, supporting the non-inferiority of Neuronox® compare to ONA. The two groups also showed no statistical differences in safety analyses. Conclusion Treatment of moderate to severe LCL with Neuronox® was effective and well-tolerated.

125O - Pembrolizumab + chemotherapy for advanced G/GEJ adenocarcinoma (GC): The phase III KEYNOTE-062 study

125O - Pembrolizumab + chemotherapy for advanced G/GEJ adenocarcinoma (GC): The phase III KEYNOTE-062 study

Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial

Prasugrel, a novel P2Y12 receptor antagonist, has been shown to be more effective than clopidogrel for preventing cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. We investigated the dose–response antiplatelet effects of prasugrel compared with clopidogrel in Japanese patients with non-cardioembolic stroke. The influence of cytochrome P450 (CYP) polymorphisms on the antiplatelet effects of both drugs was also compared. In this multicenter randomized active-control comparative study, patients were randomized to receive prasugrel 2.5 mg, 5 mg, or 7.5 mg (double blind) or clopidogrel 75 mg (open label) once daily for 14 days. The primary endpoint was inhibition of platelet aggregation (IPA) in response to adenosine diphosphate 20 μM within 8 h of study drug administration on day 14. Of the 66 patients randomized, data from 63 (prasugrel 2.5 mg, 5 mg, and 7.5 mg groups, n = 14, 16, and 18, respectively; clopidogrel group, n = 15) were used in the pharmacodynamic assessment. IPA (arithmetic mean ± SD) after prasugrel administration increased dose-dependently (33 ± 9%, 44 ± 11%, and 53 ± 14%, at 2.5 mg, 5 mg, and 7.5 mg, respectively) and was higher in these groups than after clopidogrel (23 ± 16%). In a subgroup of CYP2C19 intermediate metabolizers, IPA was higher in the prasugrel 5 mg and 7.5 mg groups than in the clopidogrel group. No death or serious adverse events were reported. Prasugrel was well tolerated at doses up to 7.5 mg/day and had antiplatelet effects higher than those of clopidogrel 75 mg/day. CYP2C19 polymorphisms may have reduced clopidogrel-induced IPA.

Schoolchildren's Compensatory Strategies and Skills in Relation to Attention and Executive Function App Training.

BackgroundGiven the importance of attention and executive functions (EF) in children’s behavior, programs aimed at improving these processes are of special interest. Nexxo-training combines the use of the Nexxo touchscreen application (inhibition and vigilance tasks) with procedural metacognitive strategies (imparted by an instructor) for all the individuals using the app, regardless of their level of ability, plus compensatory strategies based on individual child performance. This study presents an analysis of the compensatory strategies that schoolchildren (aged 6–8 years old) receive when experiencing difficulties with EF tasks, in addition to an analysis of the developmental factors and cognitive skills that may modulate EF task performance.MethodsFor this study, we use data from a previous randomized active-controlled study (under review), in which forty-six typically developing children aged between 6 and 8 years old (24 girls/22 boys) were enrolled in the training group. The selected children were in the 1st grade (n = 28, = 78.32 ± 4.037 months) and 3rd grade of primary education (n = 18, = 102.11 ± 3.445). We collected data on EF training performance, compensatory strategies needed and neuropsychological assessments.ResultsA total of 80.43% participants required some form of compensatory strategy during training. Regarding required compensatory strategies, those who had lower scores in EF training needed more compensatory strategies, in particular, instructional comprehension (r = −0.561, p < 0.001 for inhibition-tasks; r = −0.342, p < 0.001 for vigilance-tasks). Concerning developmental factors, age significantly predicted better performance in both EF tasks (β = 0.613, p < 0.001 for inhibition; β = 0.706, p < 0.001 for attention). As regards task performance, those with better performance in inhibition tasks also had better performance in vigilance tasks (r = 0.72, p < 0.001). Finally, regarding cognitive skills, participants with higher performance in fluid intelligence (Q1, n = 12) had higher scores (U = 14.5, p < 0.05) than the group with the lowest performance (Q4, n = 11) in vigilance.ConclusionAs previous literature suggests, inhibition is one of the core processes of EF. Therefore, we should focus training on the core EF processes. Inhibition and vigilance are closely related processes. In terms of the use of compensatory strategies, these are more needed for participants with lower levels of performance in inhibition or vigilance. Regarding strategy analysis, instructional comprehension and self-instruction (goal setting and planning) seem to be the most useful strategies for those with difficulties in inhibitory and vigilance task performance. Regarding development, as expected, age moderates task performance in inhibition and attention. Finally, cognitive skills, such as fluid intelligence and cognitive flexibility, predicted better results in attention. EF training using not only an app, but also compensatory strategies based on user performance, is a new research direction offering more opportunities to generalize EF training in everyday life.

Effects of the Propeller Advance Ratio on Delta Wing UAV Leading Edge Vortex

Delta wing is a triangular-shaped platform that can be applied into the unmanned aerial vehicle (UAV) or drone applications. However, the flow above the delta wing is governed by complex leading-edge vortex structures which result in complicated aerodynamics behaviour. At higher angles of attack, the vortex burst can take place when the swirling flow is unable to sustain the adverse pressure gradient. More studies are needed to understand these vortex phenomena. This paper addresses an experimental study of active flow control called propeller on a generic 55° swept angle sharp-edged delta wing model. In this experiment, a propeller was placed at two different locations. The first location was at the apex of the wing while the second position was at the rear of the wing. The experiments were conducted in a 1.5 × 2.0 m2 closed-loop wind tunnel facility at Universiti Teknologi Malaysia. The freestream velocities were set at 20 m/s and 25 m/s. The research consisted of an intensive surface pressure measurement above the wing surface to investigate the effects of rotating propeller towards the leading-edge vortex. The experiments were divided into four configurations. The clean wing configuration was performed without the propeller and followed by pusher-propeller configuration using 10-inch 9-inch propellers. The final configuration was the tractor-propeller with a 10-inch propeller. The results emphasise the influences of the propeller size and its location corresponding to vortex properties above the delta-winged UAV model. The findings had indicated that the vortex peak is increased when the propeller is installed for both pusher and tractor configurations. The results also indicate that the pressure coefficient is increased when the propeller advance ratio increases.

Effects of ruxolitinib cream on pruritus and quality of life in adult patients with atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study

Effects of ruxolitinib cream on pruritus and quality of life in adult patients with atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study

DIAGNOSIS AND OUTCOMES IN PATIENTS WITH ATYPICAL PATHOGENS IN A PHASE-3 COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA TRIAL COMPARING DELAFLOXACIN TO MOXIFLOXACIN

SESSION TITLE: Monday Electronic Posters 1 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: An etiological agent is often not identified at the time of diagnosis of community-acquired bacterial pneumonia (CABP) and as such, the Infectious Diseases Society of America/American Thoracic Society Guidelines recommend that empirical treatment cover atypical pathogens. Fluoroquinolones (FQ) have a spectrum of activity that covers gram-positive, gram-negative and atypical pathogens common in CABP. Delafloxacin (DLX) is a new FQ with activity against many Gram-positive FQ-resistant strains. A Phase 3 global, randomized, double-blind, active-controlled study was recently completed to evaluate IV-to-oral DLX compared with moxifloxacin (MOX) in the treatment of CABP. We report the clinical outcomes among patients with atypical pathogens. METHODS: CABP patients were randomized to receive 5-10 days of either DLX or MOX and could switch from IV to oral dosing after Day 3. Serologic diagnosis of Legionella pneumophila (Lp), Mycoplasma pneumoniae (Mp), and Chlamydophila pneumoniae (Cp) was made using paired acute and convalescent sera showing at least a 4-fold increase in titer. Additionally, Lp could be diagnosed by sputum culture or urinary antigen and Mp could be diagnosed by culture of oropharyngeal swabs. Susceptibility testing was performed on Lp and Mp isolates. Efficacy assessments were performed at 96 (±24) hours for Early Clinical Response (ECR) and at the Test of Cure (TOC) visit 5-10 days after the end of treatment. RESULTS: 859 patients were enrolled from sites in 18 countries, and a microbiological diagnosis (all pathogens) was established in 60.5% of patients. In the patients with baseline pathogens, Lp, Mp and Cp were detected in 11.9, 12.5 and 7.9% of these patients, respectively. Overall, 13.1% of microbial diagnoses were monomicrobial infections with atypical pathogens. DLX had potent activity against Mp and Lp. The DLX MIC90 was 0.5 μg/mL for Mp and the MICs ranged from 0.00025-0.001 μg/mL (n=4) for Lp. Overall DLX was non-inferior to MOX for the treatment of CABP in the primary outcome of ECR and by-pathogen success rates were high. In the evaluable population, ECR (DLX vs. MOX) was 93.1% vs. 87.5% for Lp, 85.7% vs. 96.7% for Mp, and 96.0% vs 87.5% for Cp. At the TOC visit, clinical success was 93.1% vs. 100% for Lp, 96.7% vs. 100% for Mp, and 100% vs 100% for Cp. CONCLUSIONS: Atypical pathogens were frequently identified in this Phase 3 study in CABP, including as monomicrobial infections. DLX, which is approved for treatment of acute bacterial skin and skin structure infections in the US, was confirmed as efficacious in monotherapy for CABP and provided comparable outcomes to MOX for the treatment of patients with atypical pathogens. CLINICAL IMPLICATIONS: DLX may be a useful treatment option for monotherapy in CABP on either an inpatient or outpatient basis when empirical coverage of atypical pathogens is desired. DISCLOSURES: Employee relationship with Melinta Please note: >$100000 Added 03/03/2019 by Sue Cammarata, source=Web Response, value=Salary Employee relationship with Melinta Therapeutics, Inc. Please note: >$100000 Added 03/04/2019 by Kara Keedy, source=Web Response, value=Salary Stock holder relationship with Melinta Therapeutics, Inc. Please note: $1001 - $5000 Added 03/12/2019 by Kara Keedy, source=Web Response, value=stock Employee relationship with Melinta Therapeutics Please note: >$100000 Added 03/12/2019 by Laura LAWRENCE, source=Web Response, value=Salary No relevant relationships by Yang Li, source=Web Response Employee $100000 Added 03/12/2019 by Sandra McCurdy, source=Web Response, value=Salary<br former employee relationship with Melinta Therapeutics Please note: >$100000 Added 03/12/2019 by Ashley Nenninger, source=Web Response, value=salary and stock Employee relationship with Melinta Therapeutics, Inc. Please note: >$100000 Added 03/12/2019 by Megan Quintas, source=Web Response, value=Salary Employee relationship with Melinta Therapeutics Inc Please note: >$100000 Added 03/12/2019 by Amanda Sheets, source=Web Response, value=Salary Stock holder relationship with Melinta Therapeutics Inc Please note: $1-$1000 Added 03/12/2019 by Amanda Sheets, source=Web Response, value=Consulting fee Removed 03/12/2019 by Amanda Sheets, source=Web Response Stock holder relationship with Melinta Therapeutics Inc Please note: $1001 - $5000 Added 03/12/2019 by Amanda Sheets, source=Web Response, value=Stock

716 Early Clinical Response and Remission With Vedolizumab Versus Adalimumab in Ulcerative Colitis: Results From VARSITY

INTRODUCTION: VARSITY is the first head-to-head trial comparing the efficacy and safety of 2 biologic therapies, vedolizumab (VDZ) and adalimumab (ADA), in patients with moderately to severely active ulcerative colitis (UC). We previously reported significantly higher rates of clinical remission (31.3% vs 22.5%; P = 0.0061) and endoscopic improvement (39.7% vs 27.7%; P = 0.0005) at Week (Wk) 52 with VDZ vs ADA. 1 METHODS: VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-controlled study (NCT02497469; EudraCT 2015-000939-33). Here we report the predefined, exploratory endpoints of early clinical response and clinical remission (defined in the Table 1) within the first 14 wks, as well as durable clinical remission (patients in clinical remission at Wk 14 and Wk 52). RESULTS: A total of 769 patients received ≥1 dose of VDZ (n = 383) or ADA (n = 386). Baseline characteristics were comparable between the 2 groups. A trend for separation in clinical response started to emerge at Wk 6 favoring VDZ vs ADA. Clinical response at Wk 14 favored VDZ vs ADA (257 [67.1%] vs 177 [45.9%]; treatment difference 21.2%). More patients achieved clinical remission at Wk 14 on VDZ vs ADA (102 [26.6%] vs 82 [21.2%]; treatment difference 5.3%). Patients on VDZ achieved higher rates of durable clinical remission (70 [18.3%] vs 46 [11.9%]); laboratory results correlated with these findings. Post hoc analyses showed a larger mean (standard deviation) change of C-reactive protein (CRP) from baseline to Wk 14 (−32.88 [155.77] nmol/L VDZ vs −3.35 [260.81] nmol/L ADA) and to Wk 52 (−50.87 [174.76] nmol/L VDZ vs −37.21 [169.17] nmol/L ADA) in favor of VDZ. Greater mean declines in fecal calprotectin (FCP) levels were seen in patients on VDZ compared with ADA (Wk 14: −1,551.3 [6,236.70] mg/kg VDZ vs −1,167.6 [4,647.67] mg/kg ADA; Wk 52: −2,187.3 [7,440.42] mg/kg VDZ vs −1,846.6 [4,560.55] mg/kg ADA). CONCLUSION: Patients on VDZ had numerically higher rates of both clinical response and clinical remission by Wk 14 compared with ADA. Patients on VDZ also achieved higher rates of durable clinical remission compared with ADA. CRP and FCP results correlated with these findings. These data on early clinical response and clinical remission, as well as durable remission, further support the use of VDZ over ADA in patients with moderately to severely active UC.

P1935Pharmacokinetic and pharmacodynamic assessment of a lipid-based aspirin formulation: results of a prospective, randomised, crossover study

Abstract Objectives Aspirin, or acetylsalicylic acid (ASA), can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer, underscoring the need for ASA formulations with a more favorable safety profile while maintaining an effective pharmacologic profile. A liquid formulation using a novel pharmaceutical lipid aspirin complex (PL-ASA) has been designed to prevent the disruption of the protective mucosal bilayer. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with traditional, immediate release aspirin (IR-ASA). Methods In this active-control crossover study, 16 healthy volunteers were randomized to receive a single dose of either IR-ASA 325 mg or PL-ASA 325 mg in a sequential fashion with a 2-week washout period between treatment assignments. The primary objectives of the study were to assess PK (i.e., plasma salicylic acid levels) and PD (i.e., serum thromboxane B2 levels) bioequivalence over a 24–hour period after drug administration, of PL-ASA and IR-ASA using established criteria. Results The PK parameter values were similar for PL-ASA and IR-ASA, with median AUC 0-t and Cmax values nominally higher for PL-ASA. Log-transformed PK parameters meeting FDA-criteria for bioequivalence (80% to 125%) are provided in the Table. Serum thromboxane B2 levels were similar for PL-ASA and IR-ASA, with Cmin values below 3.1 ng/mL (cut-off associated with decreased cardiovascular events) for both drugs. Both drugs also showed &gt;99% inhibition of serum thromboxane B2 levels (≥95% inhibition represents the cut-off to define aspirin responders). Several secondary PK/PD parameters showed similarities between the two drugs (data not shown). Overall, these findings support functional and clinical equivalence between PL-ASA and IR-ASA. PK Results Parameter Ratio (PL-ASA/IR-ASA) 90% Confidence Interval AUC0-t 96.51 89.24, 104.37 Cmax 103.73 92.06, 116.89 Conclusions PL-ASA's novel liquid formulation has similar PK and PD performance compared with IR-ASA. The improved endoscopic safety profile of PL-ASA coupled with its pharmacologic efficacy equivalent to IR-ASA may result in an improved benefit-risk performance, warranting evaluation in future trials. Acknowledgement/Funding PLx Pharma, Inc.

P.336Vision DMD: a phase IIb randomized, double-blind, parallel group, placebo- and active-controlled study to assess the efficacy and safety of vamorolone in boys with Duchenne muscular dystrophy

Vamorolone is a first-in-class steroid that shows the anti-inflammatory efficacy of glucocorticoids while reducing adverse effects of glucocorticoids. Vamorolone, unlike glucocorticoids (prednisone and deflazacort), also shows mineralocorticoid receptor antagonist activity and membrane stabilizing properties. VBP15-004 is a Phase IIb, randomised, double blind, parallel group, placebo and active (prednisone 0.75mg/kg/day) controlled study of two doses of vamorolone in 120 steroid naïve, ambulant DMD boys aged 4 to <7 years. The study primary objectives are to evaluate safety and tolerability of daily doses of vamorolone of 2.0 and 6.0 mg/kg/day and to compare its efficacy (Time to Stand from supine) over a 24-week treatment period vs. placebo. Secondary objectives include additional measures of strength and function (efficacy), and measures of safety. The study includes innovative outcome measures assessing feasibility and clinical relevance for use in future clinical trials including: exploratory safety and efficacy pharmacodynamic biomarkers; novel evaluation of the impact of vamorolone and prednisone on bone health and turnover; mobile health band study investigating the feasibility of wearable healthcare technology for recording activity data; innovative application program for consenting/assenting patients designed to provide information to young children about research and the clinical trial. The study, which opened in August 2018, has been designed in collaboration with patient organisations and is being conducted in 34 sites across 11 countries (USA, Canada, UK, Israel, Australia, Sweden, Czech Republic, Belgium, Spain, Greece, Netherlands). Vamorolone has been developed by ReveraGen Biopharma under a venture philanthropy model, in partnership with international non-profit foundations, and the US and EU governments.

Experimental Study of Active T-Foil Control of Longitudinal Motions of a Trimaran Hull in Irregular Waves

High-speed ships often experience over larger ship motions in waves. Therefore, highspeed ships without motion control hardly have practical commercial values. Recent years saw wider adoptions of T-foils on high-speed ships, which greatly improve ship performances in waves. In this study, we designed a series of model tests to study the motion-reducing effects of T-foils in waves. Heaves, pitches, and bow accelerations are quantities to be measured in the experimental tests. The study shows that the reduction effects of T-foil-controlled longitudinal motions of a trimaran model are prominent. Comparing with naked model tests, it is found that active T-foil controls may reduce motions of trimaran ships in irregular waves by about 20–30%. In the most favorable case, the reduction is as high as 51%. This study shows that installation of T-foils may dramatically reduce the motions and, thus, provide an efficient control tool to mitigate ship motions in waves. The main aims of the present study were to provide an experimental setup for model testing of an active T-foil control system and determine the control equations. Although the control and actuation systems designed in this study are simple, they do produce the required effects. The model-tested control equations can be used for high-speed foil-type ship design directly if proper similarity ratios are used to project the model test results to real ships. 1. Introduction Increasing the length-to-beam ratio is one of the most effective ways to reduce wave-making resistance so that high speed can be achieved (Ackers et al. 1998). High-speed ships with very slender hulls are, however, not stable. Placing two small side hulls on the port and starboard with displacements less than 10% of the total ship displacements improves the ship's stability greatly. This simple consideration led to the fast development of trimaran hull forms in recent years (Coppola &amp; Mandarino 2001; Degiuli et al. 2003; Oh et al. 2005). Encouraged by the successful sea trials of the 127-m-long littoral combat ship Independence at the speed of 50 knots, researchers move forward to search for new technology to improve the motion performances of trimaran hull forms in waves (Li et al. 2002; Hebblewhite et al. 2007; Jia et al. 2009). This is because high-speed ships are faced with the big challenge of severe oscillations in waves. Too large motion responses in waves would counterbalance the high-speed benefits. Therefore, motion control is crucial for high-speed trimaran ships.

Efficacy of levetiracetam as the first line anti- epileptic drug in management of neonatal seizures

Background: Neonatal seizure management has not changed much in the last 50 years. Neuronal apoptosis in animal models and cognitive impairment in human subjects has been reported with the use of Phenobarbitone. Levetiracetam is advantageous as it is effective, well tolerated and has least drug interactions.Methods: This double blinded, randomized, parallel group, active controlled study was conducted among 66 neonates in the Neonatal intensive care unit of a tertiary care hospital for a period of 18 months. Neonates with seizures fulfilling the inclusion criteria were treated either with Phenobarbitone or Levetiracetam. Seizure control was defined as no seizure activity within 40 minutes of the administration of the first drug. Failure of first line agent was treated with Phenytoin. Neonates were observed for a period of 14 weeks for recurrence of seizure and any serious adverse effects.Results: Effective seizure control was achieved in 64.7% neonates in Levetiracetam group as compared to 31.2% in Phenobarbitone group (p &lt;0.05). Early resumption of breast feeds within 6 hours of therapy was achieved in 73.5% neonates treated with Levetiracetam compared to 31.2% neonates treated with Phenobarbitone (p value = 0.001).Conclusions: Levetiracetam is a promising alternative as first line Anti-epileptic drug in neonates with seizures. Prolonged sedation was the adverse effect noted to Phenobarbitone that made breast feeding and neuro- assessment difficult. No serious adverse effects were seen with Levetiracetam.

HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study

PurposeCurrently available local anesthetics have not demonstrated sufficient analgesia beyond 12–24 h postoperatively. The purpose of the study was to assess the safety and efficacy of HTX-011 (bupivacaine and meloxicam in Biochronomer® polymer technology), a long-acting investigational anesthetic, in reducing both postoperative pain over 72 h and postoperative opioid use compared to bupivacaine hydrochloride (HCl).MethodsA phase 3, randomized, double-blind, active-controlled multi-center study (EPOCH 2; NCT03237481) in subjects undergoing unilateral open inguinal herniorrhaphy with mesh placement was performed. Subjects randomly received a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl, or saline placebo prior to closure.ResultsThe study evaluated 418 subjects, and the primary and all key secondary efficacy endpoints were in favor of HTX-011. HTX-011 reduced mean pain intensity by 23% versus placebo (primary endpoint; p < 0.001) and by 21% versus bupivacaine HCl (p < 0.001) with significant reductions in the number of patients experiencing severe pain. Opioid consumption over 72 h was reduced by 38% versus placebo (p < 0.001) and 25% versus bupivacaine HCl (p = 0.024). Overall, 51% of HTX-011 subjects were opioid-free through 72 h (versus 22% for placebo [p < 0.001] and 40% for bupivacaine HCl [p = 0.049]). HTX-011 was generally well-tolerated with fewer opioid-related adverse events reported compared to the bupivacaine HCl and placebo and no evidence of local anesthetic systemic toxicity.ConclusionsHTX-011 demonstrated significant improvement in postoperative pain control and a clinically meaningful reduction in opioid consumption when compared to the most widely used local anesthetic, bupivacaine HCl.

Pharmacokinetic/pharmacodynamic assessment of a novel, pharmaceutical lipid\u2013aspirin complex: results of a randomized, crossover, bioequivalence study

Aspirin (acetylsalicylic acid, ASA) can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer. A liquid formulation of a novel pharmaceutical lipid–aspirin complex (PL-ASA) was designed to prevent this disruption. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with immediate release aspirin (IR-ASA). In this active-control crossover study, 32 healthy volunteers were randomized to receive 1 of 2 dose levels (a single dose of 325 mg or 650 mg) of either PL-ASA or IR-ASA. After a 2-week washout period between treatment assignments, subjects received a single dose of the alternative treatment, at the same dose level. The primary objectives of the study were to assess, for PL-ASA and IR-ASA at 325 mg and 650 mg dose levels, PK and PD bioequivalence, and safety, over a 24–h period after administration of both drugs. PK parameters were similar for PL-ASA and IR-ASA, and met FDA-criteria for bioequivalence. Regarding PD, both drugs also showed Cmin TxB2 values below 3.1 ng/mL (cut-off associated with decreased cardiovascular events) and > 99% inhibition of serum TxB2 ( ≥ 95% inhibition represents the cut-off for aspirin responders) along with similar results in several secondary PK/PD parameters. There were no serious adverse events or changes from baseline in vital signs or laboratory values in either of the 2 treatment groups. PL-ASA’s novel liquid formulation has similar PK and PD performance compared with IR-ASA, supporting functional and clinical equivalence. These data coupled with the improved gastric safety of PL-ASA suggest that this novel formulation may exhibit an improved benefit-risk profile, warranting evaluation in future trials.Clinical trial registration:http://www.clinicaltrials.gov. Unique Identifier: NCT04008979