A Single Supratherapeutic Dose Of Atogepant Does Not Affect Cardiac Repolarization In Healthy Adults: Results From A Randomized, Single-Dose, Phase 1 Crossover Trial
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT(2021)
摘要
Atogepant is a selective, oral calcitonin gene-related peptide receptor antagonist in development for preventive treatment of migraine. This randomized, double-blind, phase 1 crossover study evaluated the cardiac repolarization effect of a single supratherapeutic (300 mg) atogepant dose vs placebo in healthy adults. Moxifloxacin 400 mg was the open-label active control. The primary end point was a change from baseline in Fridericia-corrected QT intervals (Delta QTcF). Sixty participants were randomized to atogepant 300 mg, placebo, and moxifloxacin; 59 (98.3%) completed all interventions. Assay sensitivity was confirmed: lower 90% confidence interval limit for QTcF interval change from baseline (Delta Delta QTcF) for moxifloxacin was >5 millisecond vs placebo at prespecified 2-, 3-, and 4-hour time points. Following single-dose atogepant 300 mg, mean atogepant Delta Delta QTcF and upper 90% confidence interval limits were lower than the 10-millisecond threshold at all time points. Atogepant mean peak plasma concentration was 3197 ng/mL, area under the concentration-time curve from time 0 to time t was 16 640 ng center dot h/mL, area under the concentration-time curve from time 0 to 24 hours was 16 607 ng center dot h/mL, and median time to peak plasma concentration was 2.1 hours. The incidence of adverse events was low; no serious adverse events or elevations of liver enzymes were reported. Overall, a single supratherapeutic dose of atogepant was safe and did not impact cardiac repolarization in healthy participants.
更多查看译文
关键词
atogepant, calcitonin gene–, related peptide receptor antagonist, cardiac repolarization, migraine disorders, thorough QT study
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要