Abstract Details

Title Results of a Phase 1, Open-label, Single-dose, Parallel-group Study of Rimegepant 75 mg in Subjects with Hepatic Impairment

Topic Headache

Presentation(s) P1 - Poster Session 1 (12:00 PM-1:00 PM)

Poster/Presentation
Number 7-006

Objective Determine the effect of hepatic impairment on the pharmacokinetics (PK) of a single 75 mg dose of rimegepant, a small molecule CGRP receptor antagonist with demonstrated efficacy and safety in migraine.

Background Hepatic impairment can have clinically significant effects on the PK of migraine medications.

Design/Methods This was a 2-center, Phase 1, open-label, single-dose, 4-group PK study. Subjects included adults aged ≥18 and ≤80 years, with BMI ≥18.0 and ≤40.0 kg/m²; weight ≥50.0 kg (males) and ≥45.0 kg (females); and a score of 0 on the Sheehan Suicidality Tracking Scale (S-STS). They were grouped by degree of hepatic impairment based on Child-Pugh score: normal (controls); mild (5-6 points); moderate (7-9 points); and severe (10-15 points). Healthy subjects were matched to hepatically impaired subjects based on gender, age, and BMI. The primary PK endpoints were AUC_0-t, AUC_0-inf, and C_max. Subjects received a single 75 mg oral dose of rimegepant under fasting conditions.

Results Thirty-six subjects were enrolled, treated, completed the study, and analyzed for safety and PK. The PK results in subjects with mild or moderate hepatic impairment were similar to controls. In subjects with severe hepatic impairment, log-transformed ratios (severe impairment / controls) were 202.25 (90% CI: 154.30, 265.10; p<0.001) for AUC_0-t; 202.21 (90% CI: 154.20, 265.17; p<0.001) for AUC_0-inf; and 189.14 (90% CI: 132.11, 270.80; p=0.009) for C_max. Three (8.3%) subjects reported at least 1 TEAE: 2 with normal hepatic function and 1 with severe hepatic impairment. No event was reported in more than 1 subject, and all events were reported as mild in intensity.

Conclusions The mild or moderate hepatic impairment groups and matched controls showed no notable differences in rimegepant exposure. Subjects with severe hepatic impairment had approximately 2-fold increases in AUC and Cmax compared with matched controls. Rimegepant was well tolerated in healthy adults and in subjects with hepatic impairment.

Authors/Disclosures
PRESENTER	No disclosure on file
	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.
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 received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Collima LLC. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has stock in Biohaven Ltd.. Dr. Croop has stock in Actio Biosciences, Inc. . Dr. Croop has received research support from Pfizer Inc. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.