A Study to Learn About the Study Medicine Called Rimegepant in Adults When Used for the Prevention of Chronic Migraine

This Phase 3, multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy, safety, and tolerability of rimegepant 75 mg administered once daily for the preventive treatment of chronic migraine in adults. Approximately 400 participants with chronic migraine will complete a 28-day Observation Phase and then be randomized in a 1:1 ratio to receive either rimegepant 75 mg or placebo during a 12-week Double-Blind Treatment (DBT) Phase.

The primary objective is to determine whether once-daily rimegepant is superior to placebo in reducing monthly migraine days in adults with chronic migraine. Secondary objectives include evaluation of migraine responder rates, headache frequency and severity, acute migraine medication use, quality of life, headache-related disability, work productivity, cognitive functioning, and patient-reported improvement.

Participants will record migraine and headache information using an electronic diary and will complete protocol-specified efficacy and safety assessments throughout the study. Safety evaluations will include monitoring of adverse events, clinical laboratory assessments, vital signs, electrocardiograms, and other protocol-defined safety measures.

Eligible participants who complete the DBT Phase and remain eligible may enter a 12-week Open-Label Extension (OLE) Phase, during which all participants will receive open-label rimegepant 75 mg once daily. During the OLE Phase, participants may also take an additional dose of rimegepant 75 mg for the acute treatment of breakthrough migraine attacks, up to 10 doses per month. Following completion or discontinuation of study treatment, participants will enter a 28-day Follow-Up Phase.

The study is designed to determine whether once-daily rimegepant provides superior efficacy to placebo for the preventive treatment of chronic migraine in adults and to further characterize the safety and tolerability profile of daily rimegepant administration.

Inclusion criteria

• Male or female participants ≥18 years of age.
• Diagnosis of chronic migraine, with or without aura, according to International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria.
• History of migraine for at least 1 year before screening.
• Migraine onset before 50 years of age and chronic migraine onset before 65 years of age.
• Migraine attacks lasting 4 to 72 hours when untreated or unsuccessfully treated.
• During the 3 months prior to screening, an average of:
• ≥15 monthly headache days (MHDs),
• including ≥8 monthly migraine days (MMDs),
• and ≥1 non-headache day per month.
• Completion of the Observation Phase and fulfillment of all protocol-defined eligibility requirements prior to randomization.
• Willing and able to comply with study procedures, including completion of the electronic diary.

Exclusion criteria

• Prior use of rimegepant for migraine prevention.
• History of treatment failure of:

• 2 gepants, or
• 2 CGRP-targeting biologics, or
• 1 gepant and ≥1 CGRP-targeting biologic.
• Failure of >4 migraine preventive medications, including at least 2 with different mechanisms of action.
• Any medical or psychiatric condition, or clinically significant laboratory abnormality, that in the investigator's judgment may increase risk to the participant or interfere with study participation or interpretation of results. This includes, but is not limited to, uncontrolled hypertension or a history of Raynaud's phenomenon.
• Pregnant, breastfeeding, planning to become pregnant, or planning to initiate breastfeeding during the study.
• Positive amphetamine screening result unless attributable to prescribed stimulant therapy that has been stable for at least 3 months prior to Visit 1 and is expected to remain stable throughout study participation.
• Use of investigational products or participation in another clinical study within protocol-defined exclusion windows.
• Any other condition that, in the opinion of the investigator or sponsor, would make study participation unsafe or compromise study conduct.