Journal of Pain Research (Jul 2024)
Efficacy and Safety of Rimegepant 75 mg Oral Tablet, a CGRP Receptor Antagonist, for the Acute Treatment of Migraine: A Randomized, Double-Blind, Placebo-Controlled Trial
Abstract
Richard B Lipton,1 Alexandra Thiry,2 Beth A Morris,3 Robert Croop3 1Department of Neurology and the Montefiore Headache Center, Albert Einstein College of Medicine, Bronx, NY, USA; 2Biostatistics, Pfizer, Inc., New York, NY, USA; 3Clinical Operations (BM) and Development (RC), Biohaven Pharmaceuticals, Inc., New Haven, CT, USACorrespondence: Richard B Lipton, Montefiore Headache Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Van Etten 3C12, Bronx, NY, 10461, USA, Tel +1 718-430-3896, Email [email protected]: This study compared the efficacy, tolerability, and safety of rimegepant 75 mg oral tablet – a small molecule calcitonin-gene receptor peptide (CGRP) receptor antagonist – with placebo in the acute treatment of migraine.Methods: This double-blind, randomized, placebo-controlled trial enrolled adults aged ≥ 18 years with at least a 1-year history of migraine. Participants randomized to rimegepant 75 mg oral tablet or placebo treated a single migraine attack of moderate or severe pain intensity. The coprimary endpoints, pain freedom and freedom from the most bothersome symptom ([MBS] nausea, photophobia, or phonophobia) at 2 hours postdose, were evaluated using Mantel–Haenszel risk estimation.Results: Of the 1485 participants enrolled, 1162 (78.2%) were randomized to rimegepant (n = 582) or placebo (n = 580). Most participants (85.5%) were female; the population had a mean (SD) age of 41.6 (12.2) years and a history of 4.7 (1.8) migraine attacks per month. At 2 hours postdose, rimegepant-treated participants had higher pain freedom rates (19.2% [104/543] vs 14.2% [77/541]; risk difference 4.9; 95% confidence interval [CI] 0.5 to 9.3; P=0.0298) and MBS freedom rates (36.6% [199/543] vs 27.7% [150/541]; risk difference 8.9; 95% CI 3.4 to 14.4; P=0.0016) than placebo-treated participants. Rimegepant-treated participants also had higher rates of pain relief (56.0% [304/543] vs 45.7% [247/541]; risk difference 10.3; 95% CI 4.4 to 16.2, P=0.0006) at 2 hours postdose. The most common adverse events were nausea (0.9% [5/546] vs 1.1% [6/549]) and dizziness (0.7% [4/546] vs 0.4% [2/549]). No signal of drug-induced liver injury due to rimegepant was identified.Conclusion: Rimegepant 75 mg oral tablet was effective in the acute treatment of migraine. Tolerability and safety were similar to placebo, with no evidence of hepatotoxicity.Trial Registration: Clinicaltrials.gov Identifier: NCT03235479.Plain Language Summary: Researchers wanted to know if rimegepant 75 mg is effective and safe for the acute treatment of migraine. They gave half the participants rimegepant and half placebo and waited 2 hours. Then, they measured the percentages of participants whose headache and most bothersome migraine symptom besides pain (nausea, sensitivity to light or sound) were gone. They also measured side effects to make sure rimegepant is safe.The study included 1084 adults with migraine, 927 (86%) of whom were women. Two hours after taking the medicine: pain freedom was 19% with rimegepant and 14% with placebo. Freedom from the most bothersome symptom was 37% with rimegepant and 28% with placebo. Pain relief rates, defined as the transition from moderate or severe pain to pain that was mild or absent, occurred in 56% with rimegepant and 46% with placebo. The most common side effects were nausea and dizziness, which affected fewer than 1% of rimegepant patients. Rimegepant 75 mg was more effective than placebo for migraine, with similar tolerability and safety.Keywords: migraine, acute, CGRP, rimegepant, efficacy, safety, tablet
