Efficacy and Safety Study of Rimegepant in Episodic Migraine Prevention With Multiple Dosing Regimens

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the efficacy and safety of daily and every other day dosing of rimegepant to placebo as a preventive treatment for episodic migraine.

Official Title
-----------------
A Phase 4 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rimegepant in Episodic Migraine Prevention With Multiple Dosing Regimens

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Drug: Rimegepant 75mg daily dosing
* Drug: Rimegepant 75mg every other day dosing
* Drug: Placebo comparator dosing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1) Target Population: Subject has at least 1 year history of episodic migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following: Age of onset of migraines prior to 50 years of age Migraine attacks, on average, lasting 4-72 hours if untreated Per subject report, 4-14 migraine attacks per month within the last 3 months prior to the Screening Visit (month is defined as 4 weeks for the purpose of this protocol Exclusion Criteria: Sex and Reproductive Status: WOCBP who are unwilling or unable to use an acceptable contraceptive method or abstinence to avoid pregnancy for the entire study and for 60 days after the last dose of study drug Women who are pregnant or breastfeeding Women with a positive pregnancy test at screening or prior to study drug administration Prohibited Medications: Use of prophylactic migraine medication within 30 days prior to the Screening Visit. History of use of analgesics (e.g., non-steroidal anti-inflammatory drugs [NSAIDs] or acetaminophen) on ≥ 15 days per month during the 3 months (12 weeks) prior to the Screening Visit. Use of medication accepted for treatment of acute migraine for a nonmigraine indication on ≥ 15 days per month during the 3 months (12 weeks) prior to the Screening Visit. Subjects who previously discontinued biologic migraine medication must have done so at least 6 months (24 weeks) prior to the Screening Visit. Subjects taking a prohibited medication as defined per protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rimegepant 75mg Orally Disitegrating Tablet (ODT)daily dosing<br>Double-blind Treatment Phase: Rimegepant 75 mg ODT dosed daily Open-Label Extension Phase: Rimegepant 75 mg ODT dosed daily | Drug: Rimegepant 75mg daily dosing<br>* Daily<br>|
| Experimental: Rimegepant 75mg Orally Disintegrating Tablet (ODT)every other day dosing<br>Double-blind Treatment Phase: Rimegepant 75 mg ODT every other day dosing alternating with matching placebo | Drug: Rimegepant 75mg every other day dosing<br>* Every other day<br>|
| Placebo Comparator: Placebo comparator dosing<br>Double-blind Treatment Phase: matching placebo dosed daily | Drug: Placebo comparator dosing<br>* Placebo comparator<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from the Observation Phase in the number of migraine days per month over the entire Double-blind Treatment Phase (Weeks 1-12) | Change from baseline in mean number of migraine days per month | 3 months (12 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with > 50% reduction from the Observation Phase (Weeks 1 to 12). | Number of moderate to severe migraine days per month over the entire Double-blind Treatment Phase | 3 months (12 weeks) | 
| Mean change from the Observation Phase. | Number of migraine days per month in the last 4 weeks of the Double-blind Treatment Phase. | Weeks 9 to 12 | 
| Mean change from the Observation Phase | number of migraine days per month in the first 4 weeks of the Double-blind Treatment Phase. | Weeks 1 to 4 | 
| Mean number of acute migraine-specific medication days per month. | Over the entire Double-blind Treatment Phase. Acute migraine-specific medications are triptans and ergotamine. | Weeks 1 to 12 | 
| Mean change from baseline in the Migraine-Specific Quality-of-Life Questionnaire (MSQ) restrictive role function. | Domain score of the Double-blind Treatment Phase. | At Week 12 | 
| Number and percentage of subjects with AEs by intensity. | Serious adverse events (SAEs), AEs leading to study drug discontinuation, and grade 3 to 4 laboratory test abnormalities during the Double-blind Treatment and Open-label Extension Phases. | 24 Weeks | 
| Number and percentage of subjects treated with rimegepant with AST or ALT elevations. | >3x ULN concurrent (i.e., on the same laboratory collection date) with total bilirubin > 2x ULN during the Double-blind Treatment and Open-label Extension Phases. | 24 Weeks | 
| Number and percentage of subjects treated with rimegepant with hepatic-related AEs | By intensity and hepatic-related AEs leading to study drug discontinuation during the Double-blind Treatment and Open-label Extension Phases. | 24 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Migraine, Episodic Migraine, Adult Migraine, Calcitonin Gene-related Peptide, Migraine Prevention, Migraine Prophylaxis