No clinically relevant electrocardiogram effects in a randomized TQT study of single therapeutic/supratherapeutic rimegepant doses in healthy adults

• DOI: 10.1111/cts.13727
• Publication Date: 2024-03-05T09:48:51Z
• Authors: Rajinder Bhardwaj; Michael S. Hanna; Beth A. Morris; Kyle T. Matschke; Richard Bertz; Robert S. Croop; Jing Liu
• Keywords: Therapeutics. Pharmacology; RM1-950; Articles; Public aspects of medicine; RA1-1270

A single-center, phase I, partially double-blind (double-blind regarding doses of rimegepant and placebo, open label with respect to moxifloxacin), randomized, 12-sequence, four-period crossover study therapeutic (75 mg) supratherapeutic (300 placebo moxifloxacin (400 controls was designed evaluate drug effect on the Fridericia corrected QT (QTcF) interval in healthy fasted adults. total 38 participants were randomized dosed study. Electrocardiogram (ECG) data available from 37 75-mg group, 300-mg 36 groups. Both 75- had no clinically relevant ECG parameters, including QTcF, heart rate, PR QRS interval, T-wave morphology, U-wave presence. All upper 90% confidence intervals for QTcF less than or equal 4.69 ms, well below 10-ms threshold potential clinical significance. Assay sensitivity demonstrated by moxifloxacin. Using both by-timepoint concentration-QTc analysis, a placebo-corrected change-from-baseline greater 10 ms could be excluded plasma concentrations up ~10,000 ng/mL, representing at least 10.8-fold maximum observed concentration dose rimegepant.