Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial

Atogepant is an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist under investigation for treatment of migraine. We aimed to examine a range of oral doses for safety, tolerability, and efficacy for the preventive treatment of migraine. In this double-bli...

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Published in:Lancet neurology 2020-09, Vol.19 (9), p.727-737
Main Authors: Goadsby, Peter J, Dodick, David W, Ailani, Jessica, Trugman, Joel M, Finnegan, Michelle, Lu, Kaifeng, Szegedi, Armin
Format: Article
Language:English
Subjects:
Antibodies
Calcitonin
Calcitonin gene-related peptide
Double-blind studies
FDA approval
Headache
Migraine
Nausea
Oral administration
Pathophysiology
Patient satisfaction
Peptides
Personnel
Pharmacodynamics
Prevention
Safety
Studies
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Summary:Atogepant is an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist under investigation for treatment of migraine. We aimed to examine a range of oral doses for safety, tolerability, and efficacy for the preventive treatment of migraine. In this double-blind, phase 2b/3 trial, adults (aged 18–75 years), with a history (≥1 year) of migraine and 4–14 migraine days per month, were randomly assigned 2:1:2:2:1:1 (by means of a sequence generated by the statistical programming department of the sponsor, and operationalised through an automated interactive web-based response system) to receive placebo or atogepant 10 mg once daily, 30 mg once daily, 60 mg once daily, 30 mg twice daily, or 60 mg twice daily, in matching capsules. Participants, site personnel, and all study sponsor personnel were masked to treatment allocations. The study was done in 78 academic and private practice settings in the USA. The primary outcome was change from baseline in monthly migraine days across 12 weeks of treatment using a modified intention-to-treat approach. The overall type I error rate for multiple comparisons across active treatment doses was controlled at the 0·05 level by means of a graphic approach. The main outcomes to assess safety and tolerability were adverse event recordings. The trial is registered with ClinicalTrials.gov, NCT02848326 and is completed. Between Sept 6, 2016, and April 23, 2018, of 1772 individuals screened, 834 were randomly assigned and 825 received one dose or more of study medication: 186 received placebo, 93 atogepant 10 mg once daily, 183 atogepant 30 mg once daily, 186 atogepant 60 mg once daily, 86 atogepant 30 mg twice daily, and 91 atogepant 60 mg twice daily. Overall, 714 (87%) of 825 participants were female, 628 (76%) were white, median migraine duration was 17·5 years (IQR 10·0–28·0), and 232 (28%) had previously used preventive treatment. The primary efficacy analysis included 795 patients: 178 received placebo, 92 atogepant 10 mg once daily, 182 atogepant 30 mg once daily, 177 atogepant 60 mg once daily, 79 atogepant 30 mg twice daily, and 87 atogepant 60 mg twice daily. Across the 12-week treatment period, all five atogepant groups showed significant least-squares mean (SE) change from baseline in mean monthly migraine days versus placebo: atogepant 10 mg once daily −4·0 (0·3; p=0·024), 30 mg once daily −3·8 (0·2; p=0·039), 60 mg once daily −3·6 (0·2; p=0·039), 30 mg twice daily −4·2 (0·4; p
ISSN:1474-4422
1474-4465
DOI:10.1016/S1474-4422(20)30234-9