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Abstract Details

Rimegepant Has No Clinically Relevant Effect on ECG parameters at Therapeutic and Supratherapeutic Doses: A Thorough QT Study Versus Placebo and Moxifloxacin in Healthy Subjects
Headache
P6 - Poster Session 6 (12:00 PM-1:00 PM)
7-003
Some medications can affect ion channels in cardiac cells, delaying cardiac repolarization and resulting in proarrhythmic behavior. New drugs with systemic exposure should be tested for prolongation of the QT interval.
Evaluate the effect of therapeutic and supratherapeutic concentrations of rimegepant, a small molecule CGRP receptor antagonist with demonstrated efficacy and safety in the acute treatment of migraine, on the QTcF interval.
This was a single-center, Phase 1, partially double-blind, randomized, placebo-controlled, 12-sequence, 4-period crossover study. Fasted adults aged ≥18 and ≤55 years were randomized to 1 of 12 sequences: rimegepant 75 mg (1x 75 mg + 3 placebo); rimegepant 300 mg (4x 75 mg); placebo (4x); or moxifloxacin hydrochloride 400 mg as a positive control to establish assay sensitivity. From baseline through 24 hours postdose in each treatment period, PK, safety, and ECG parameters were assessed. The primary analysis was based on placebo-corrected change from baseline in QTcF.
Of the 38 subjects randomized, 37 received rimegepant 75 mg, 38 received rimegepant 300 mg, 36 received moxifloxacin, and 36 received placebo. A single rimegepant dose of 75 mg (therapeutic) or 300 mg (supratherapeutic) had no clinically relevant effect on ECG parameters, including the HR, PR, QRS and QT/QTcF intervals. The predicted placebo-corrected change from baseline in QTcF was 0.45 msec (90% CI: -1.11, 2.01) after dosing with rimegepant 75 mg, thus excluding the protocol-specified criteria of a 10 msec increase. Results were similar with rimegepant 300 mg. There were no SAEs or AEs leading to discontinuation. No ALT or AST levels were >3x ULN, and no subjects had total bilirubin levels >2x ULN.
Therapeutic and supratherapeutic doses of rimegepant had no clinically meaningful effect on ECG parameters (ie, HR, PR, QRS, and QTcF) and the results represent a negative TQT study. Rimegepant was safe and well tolerated in healthy adults.
Authors/Disclosures
Michael Hanna, PhD (Mercury Medical Research & Writing)
PRESENTER
No disclosure on file
Vladimir Coric Vladimir Coric has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Bioahven. Vladimir Coric has stock in Biohaven. Vladimir Coric has received intellectual property interests from a discovery or technology relating to health care.
Joseph Stringfellow Joseph Stringfellow has nothing to disclose.
Andrea Ivans Andrea Ivans has received personal compensation for serving as an employee of Biohaven Pharmaceuticals.
Robert Croop, MD Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has received personal compensation for serving as an employee of Pfizer Inc.. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has stock in Biohaven Ltd.. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.