Phase 3 Double-Blind Study on Rimegepant for Intermittent Prevention of Menstrual Migraine in Women Aged 18-45

The primary objective is to confirm the superiority of rimegepant 75 mg orally disintegrating tablet (ODT) compared to placebo for the intermittent prevention of menstrual migraine attacks occurring during the 5-day perimenstrual period (PMP), when administered for 7 days per menstrual cycle. The study evaluates efficacy and safety of this intervention. Secondary objectives include:

• Further assessment of the superiority of rimegepant 75 mg ODT versus placebo for the intermittent prevention of attacks during the 5-day PMP.
• Evaluation of monthly migraine frequency based on daily headache diary data.
• Analysis of additional efficacy variables during the double-blind treatment (DBT) phase.
• Assessment of patient-reported outcomes, including productivity, function, global status, and treatment satisfaction.
• Evaluation of safety and tolerability of the 75 mg ODT dose.

This study involves 374 female participants diagnosed with menstrual migraine. The study population consists of individuals aged 18 to 45 years who possess regular menstrual cycles lasting between 24 and 34 days. Inclusion requires a minimum one-year history of migraine, with or without aura, according to the International Classification of Headache Disorders, 3rd Edition. Participants must have experienced menstrual migraine attacks during the perimenstrual period in at least two of the three menstrual cycles preceding screening. Eligible subjects may be using stable doses of permitted continuous prophylactic medication or specific forms of contraception, such as oral contraceptive tablets or an intrauterine device, provided these regimens have been maintained for a specified duration prior to the study.

This is a Phase 3, double-blind, parallel group, interventional study designed to evaluate the efficacy and safety of rimegepant 75 mg oral lyophilisate compared to a placebo for the intermittent prevention of menstrual migraine. The methodology aims to confirm the superiority of the test product when administered for 7 days per menstrual cycle during the 5-day perimenstrual period. The study design involves a screening visit to assess eligibility based on specific criteria, including age, menstrual cycle regularity, and a documented history of migraine. Following screening, participants enter the double-blind treatment phase. Primary and secondary endpoints include changes in the number of migraine days and headache days, as well as the use of acute migraine-specific medication. The total study duration is estimated to extend from September 2025 to March 2027. Participation may be discontinued if specified conditions or safety protocols necessitate early termination.

The experimental treatment consists of rimegepant, administered as a 75 mg oral lyophilisate. This medication is intended for oral administration for a duration of 7 days per menstrual cycle to investigate the intermittent prevention of menstrual migraine.

The comparator treatment is a placebo designed to match the 75 mg oral lyophilisate in appearance and administration characteristics.

The efficacy assessment focuses on the intermittent prevention of menstrual migraine. The primary endpoint is the mean change from the open-label period in the number of migraine days per 5-day perimenstrual period across each cycle of the double-blind treatment phase.

Secondary efficacy endpoints include:

• Mean change from the open-label period in the number of headache days per 5-day perimenstrual period across each cycle of the double-blind treatment phase.
• Percentage of participants achieving a 50% responder rate, defined as a ≥50% reduction from the open-label period in the number of migraine days per 5-day perimenstrual period.
• Mean change from the open-label period in the number of acute migraine medication days per 5-day perimenstrual period.
• Mean change from the open-label period in the number of acute migraine-specific medication days per 5-day perimenstrual period, as measured via eDiary.
• Mean change from the open-label period in the number of migraine days with moderate-severe functional disability per 5-day perimenstrual period.
• Mean change from the open-label period in the number of moderate-severe headache days and moderate-severe migraine days per 5-day perimenstrual period.
• Mean change from baseline in the Migraine Clinical Outcome Assessment System cognition score at post-dosing, recorded 1 day after the 7-day dosing period.
• Mean change from the open-label period in monthly migraine days, monthly headache days, and monthly acute migraine-specific medication days, normalized to 28 days across each cycle of the double-blind treatment phase.