C4951012 - BHV3000-407: a Phase 4, Randomized, Double-blind, Placebo controlled Study to Evaluate the Efficacy and Tolerability of Rimegepant for the Prevention of Migraine in Adults with a History of Inadequate Response to Oral Preventive Medications

INTERVENTION: Product Name: VYDURA 75 mg oral lyophilisate, Product Code:PRD10088770, Pharmaceutical Form: ORAL LYOPHILISATE, Other descriptive name: , Strength: , Product Name: Placebo for Rimegepant 75 mg, Product Code:N/A, Pharmaceutical Form: N/A, Other descriptive name: N/A , Strength: , Pharmaceutical form of the placebo: N/A CONDITION: migraine headaches with or without aura ; MedDRA version: 20.0Level: PTClassification code: 10027599Term: Migraine Class: 100000004852 Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: To compare the efficacy of rimegepant to placebo as an EOD dosing regimen for prophylaxis in adults with a history of inadequate response to agents across 2‐4 categories of recognized, orally‐administered migraine preventive medications as measured by the mean reduction from the Observation Phase in the number of migraine days per month (28 days) over the entire DBT Phase. Primary end point(s): Mean change from the Observation Phase in the number of migraine days per month over the entire double‐blind treatment (DBT) Phase. Secondary Objective: To compare the proportion of subjects with = 50% reduction from the Observation Phase in the number of migraine days of moderate or severe headache pain intensity per month over the entire DBT Phase (Weeks 1 to 12) between rimegepant and placebo., To compare the mean reduction from the Observation Phase in the number of migraine days per month in the first 4 weeks of the DBT Phase between rimegepant and placebo., To compare the mean reduction from the Observation Phase in the number of migraine days per month in the last 4 weeks of the DBT Phase between rimegepant and placebo., To compare the mean change from baseline in the Migraine‐Specific Quality‐of‐Life Questionnaire v 2.1 (MSQ) restrictive role function domain score at Week 12 of the DBT Phase between rimegepant and placebo., To compare the mean change from baseline in Migraine Interictal Burden Scale (MIBS) score at Week 12 of the DBT Phase between rimegepant and placebo. SECONDARY OUTCOME: Secondary end point(s):Mean change from baseline in the MIBS score at Week 12 of the DBT Phase. Secondary end point(s):Mean change from baseline in the MSQ restrictive role function domain score at Week 12 of the DBT Phase. Secondary end point(s):Mean change from the Observation Phase in the number of migraine days per month in the first 4 weeks (Weeks 1 to 4) of the DBT Phase. Secondary end point(s):Mean change from the Observation Phase in the number of migraine days per month in the last 4 weeks (Weeks 9 to 12) of the DBT Phase. Secondary end point(s):Proportion of subjects with = 50% reduction from the Observation Phase in the number of migraine days of moderate or severe headache pain intensity per month over the entire DBT Phase (Weeks 1 to 12). INCLUSION CRITERIA: Target Population: Minimum 1 year documented history of migraines (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition.3 Per self‐report, with confirmation from Investigator / supporting medical record, subjects must have: a. Migraine attacks present for more than 1 year from the Screening Visit b. Age of onset prior to 50 years of age c. Migraine attacks lasting about 4–72 hours, if untreated d. 4 to 14 migraine days, on average, across the 3 months prior to the Screening Visit e. 4 to 14 migraine days during the 28‐day Observation Phase f. Subjects must be able to distinguish migraine attacks from tension headaches g. Prior inadequate response, within 10 years of the Screening Visit, to agents across 2‐4 categories of recognized, orally‐administered migraine‐preventive medications where at least one example of prior inadequate response is due to lack of efficacy or prior intolerance (no