TY - JOUR
T1 - Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine
T2 - a randomised, phase 3, double-blind, placebo-controlled trial
AU - Croop, Robert
AU - Goadsby, Peter J.
AU - Stock, David A.
AU - Conway, Charles M.
AU - Forshaw, Micaela
AU - Stock, Elyse G.
AU - Coric, Vladimir
AU - Lipton, Richard B.
N1 - Funding Information:
PJG reports, over the past 36 months, grants and personal fees from Amgen and Eli Lilly, and personal fees from Alder Biopharmaceuticals, Allergan, Autonomic Technologies, Biohaven Pharmaceuticals, Dr Reddy's Laboratories, Electrocore, eNeura, Impel Neuropharma, MundiPharma, Novartis, Teva, Trigemina, WL Gore, MedicoLegal work, Massachusetts Medical Society, Up-to-Date, Oxford University Press, and Wolters Kluwer; and a patent magnetic stimulation for headache assigned to eNeura without fee. RBL serves on the editorial board of Neurology and Cephalalgia and as senior advisor to Headache but is not paid for his roles on Neurology or Headache; has received research support from the National Institutes of Health; receives support from the Migraine Research Foundation and the National Headache Foundation; receives research grants from Allergan, Amgen, Dr Reddy's Laboratories, and Novartis; has reviewed for the National Institute on Aging and National Institute of Neurological Disorders and Stroke; serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, Amgen, Avanir, Biohaven, Boston Scientific, Dr Reddy's Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta; receives royalties from Wolff's Headache eighth edition (Oxford Press University, 2009) and Informa; and holds stock options in eNeura Therapeutics and Biohaven Pharmaceuticals. RC, DAS, CMC, MF, EGS, and VC are employed by and own stock in Biohaven Pharmaceuticals.
Funding Information:
This trial was funded by Biohaven Pharmaceuticals, developer of rimegepant. Medical writing services were provided by Christopher Caiazza and funded by Biohaven Pharmaceuticals. The authors express their appreciation to the patients, investigators, and site staff who participated in this study. The authors also thank Francine Healy, Christopher Jensen, and Ashwini Ghatpande of Biohaven Pharmaceuticals, for careful reviews and helpful comments on the manuscript.
PY - 2019/8/31
Y1 - 2019/8/31
N2 - Background: Rimegepant, a small molecule calcitonin gene-related peptide receptor antagonist, has shown efficacy in the acute treatment of migraine using a standard tablet formulation. The objective of this trial was to compare the efficacy, safety, and tolerability of a novel orally disintegrating tablet formulation of rimegepant at 75 mg with placebo in the acute treatment of migraine. Methods: In this double-blind, randomised, placebo-controlled, multicentre phase 3 trial, adults aged 18 years or older with history of migraine of at least 1 year were recruited to 69 study centres in the USA. Participants were randomly assigned to receive rimegepant (75 mg orally disintegrating tablet) or placebo and instructed to treat a single migraine attack of moderate or severe pain intensity. The randomisation was stratified by the use of prophylactic medication (yes or no), and was carried out using an interactive web response system that was accessed by each clinical site. All participants, investigators, and the sponsor were masked to treatment group assignment. The coprimary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 h postdose. The efficacy analyses used the modified intention-to-treat population, which included all patients who were randomly assigned, had a migraine attack with pain of moderate or severe intensity, took a dose of rimegepant or placebo, and had at least one efficacy assessment after administration of the dose. The safety analyses included all randomly assigned participants who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, number NCT03461757, and is closed to accrual. Findings: Between Feb 27 and Aug 28, 2018, 1811 participants were recruited and assessed for eligibility. 1466 participants were randomly assigned to the rimegepant (n=732) or placebo (n=734) groups, of whom 1375 received treatment with rimegepant (n=682) or placebo (n=693), and 1351 were evaluated for efficacy (rimegepant n=669, placebo n=682). At 2 h postdose, rimegepant orally disintegrating tablet was superior to placebo for freedom from pain (21% vs 11%, p<0·0001; risk difference 10, 95% CI 6–14) and freedom from the most bothersome symptom (35% vs 27%, p=0·0009; risk difference 8, 95% CI 3–13). The most common adverse events were nausea (rimegepant n=11 [2%]; placebo n=3 [<1%]) and urinary tract infection (rimegepant n=10 [1%]; placebo n=4 [1%]). One participant in each treatment group had a transaminase concentration of more than 3 × the upper limit of normal; neither was related to study medication, and no elevations in bilirubin greater than 2 × the upper limit of normal were reported. Treated participants reported no serious adverse events. Interpretation: In the acute treatment of migraine, a single 75 mg dose of rimegepant in an orally disintegrating tablet formulation was more effective than placebo. Tolerability was similar to placebo, with no safety concerns. Funding: Biohaven Pharmaceuticals.
AB - Background: Rimegepant, a small molecule calcitonin gene-related peptide receptor antagonist, has shown efficacy in the acute treatment of migraine using a standard tablet formulation. The objective of this trial was to compare the efficacy, safety, and tolerability of a novel orally disintegrating tablet formulation of rimegepant at 75 mg with placebo in the acute treatment of migraine. Methods: In this double-blind, randomised, placebo-controlled, multicentre phase 3 trial, adults aged 18 years or older with history of migraine of at least 1 year were recruited to 69 study centres in the USA. Participants were randomly assigned to receive rimegepant (75 mg orally disintegrating tablet) or placebo and instructed to treat a single migraine attack of moderate or severe pain intensity. The randomisation was stratified by the use of prophylactic medication (yes or no), and was carried out using an interactive web response system that was accessed by each clinical site. All participants, investigators, and the sponsor were masked to treatment group assignment. The coprimary endpoints were freedom from pain and freedom from the most bothersome symptom at 2 h postdose. The efficacy analyses used the modified intention-to-treat population, which included all patients who were randomly assigned, had a migraine attack with pain of moderate or severe intensity, took a dose of rimegepant or placebo, and had at least one efficacy assessment after administration of the dose. The safety analyses included all randomly assigned participants who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, number NCT03461757, and is closed to accrual. Findings: Between Feb 27 and Aug 28, 2018, 1811 participants were recruited and assessed for eligibility. 1466 participants were randomly assigned to the rimegepant (n=732) or placebo (n=734) groups, of whom 1375 received treatment with rimegepant (n=682) or placebo (n=693), and 1351 were evaluated for efficacy (rimegepant n=669, placebo n=682). At 2 h postdose, rimegepant orally disintegrating tablet was superior to placebo for freedom from pain (21% vs 11%, p<0·0001; risk difference 10, 95% CI 6–14) and freedom from the most bothersome symptom (35% vs 27%, p=0·0009; risk difference 8, 95% CI 3–13). The most common adverse events were nausea (rimegepant n=11 [2%]; placebo n=3 [<1%]) and urinary tract infection (rimegepant n=10 [1%]; placebo n=4 [1%]). One participant in each treatment group had a transaminase concentration of more than 3 × the upper limit of normal; neither was related to study medication, and no elevations in bilirubin greater than 2 × the upper limit of normal were reported. Treated participants reported no serious adverse events. Interpretation: In the acute treatment of migraine, a single 75 mg dose of rimegepant in an orally disintegrating tablet formulation was more effective than placebo. Tolerability was similar to placebo, with no safety concerns. Funding: Biohaven Pharmaceuticals.
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U2 - 10.1016/S0140-6736(19)31606-X
DO - 10.1016/S0140-6736(19)31606-X
M3 - Article
C2 - 31311674
AN - SCOPUS:85070260348
VL - 394
SP - 737
EP - 745
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10200
ER -