Dose Ranging Study of Rimegepant (BMS-927711) for the Acute Treatment of Migraine

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the efficacy of rimegepant (BMS-927711) compared with placebo in the acute treatment of migraine as measured by Pain Freedom (headache pain intensity level reported as no pain) at 2 hours post dose using a four point numeric rating scale (no pain, mild pain, moderate pain, severe pain) while identifying an optimal dose to support the Phase 3 clinical trials.

Detailed Description
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Intervention Model: Parallel Versus Comparator + Placebo

Official Title
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Phase IIb: Double-Blind, Randomized, Placebo Controlled, Dose-ranging Trial of BMS-927711 for the Acute Treatment of Migraine

Conditions
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Migraine, Acute Treatment of Migraine

Intervention / Treatment
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* Drug: Rimegepant
* Drug: Placebo
* Drug: Sumatriptan


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patient with at least 1-year history of migraines (with or without aura) including the following: Migraine attacks more than 1 year with age of onset prior to 50 years of age Migraine attacks, on average, last about 4 - 72 hours if untreated No more than 8 attacks of moderate to severe intensity per month within last 3 months Patient must be able to distinguish migraine attacks from tension/cluster attacks and must have consistent migraine headaches of at least 2 migraine headaches attacks of moderate to severe intensity in each of the last 3 months Less than 15 days of headache (migraine or non-migraine) per month in each of 3 months prior to screening Male and female ≥ 18 years and ≤ age 65 No clinically significant abnormality identified on the medical or laboratory evaluation Key Exclusion Criteria: Patient has a history of basilar migraine or hemiplegic migraine Patient does not receive migraine relief from triptan migraine treatment Medications that may alter the pH of the stomach (acid reducing agents), such as H-2 antagonists, Proton Pump inhibitors (PPI), antacids History of ergotamine or triptan intake greater than/equal 10 days per month on a regular basis for greater than 3 months History of non-narcotic analgesic intake on greater then/equal 15 days per month for greater than/equal 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: Rimegepant, 10 mg<br>Participants received a single dose (one capsule) of rimegepant 10 milligram (mg) orally and three rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | Drug: Rimegepant<br>* Rimegepant capsules<br>Drug: Placebo<br>* Rimegepant placebo-matching capsules<br>|
| Experimental: Treatment B: Rimegepant, 25 mg<br>Participants received a single dose (one capsule) of rimegepant 25 mg orally; and three rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | Drug: Rimegepant<br>* Rimegepant capsules<br>Drug: Placebo<br>* Rimegepant placebo-matching capsules<br>|
| Experimental: Treatment C: Rimegepant, 75 mg<br>Participants received a single dose (one capsule) of rimegepant 75 mg orally; and three rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | Drug: Rimegepant<br>* Rimegepant capsules<br>Drug: Placebo<br>* Rimegepant placebo-matching capsules<br>|
| Experimental: Treatment D: Rimegepant, 150 mg<br>Participants received a single dose (one capsule) of rimegepant 150 mg orally; and three rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | Drug: Rimegepant<br>* Rimegepant capsules<br>Drug: Placebo<br>* Rimegepant placebo-matching capsules<br>|
| Experimental: Treatment E: Rimegepant, 300 mg<br>Participants received a single dose (two 150 mg capsules) of rimegepant 300 mg orally; and two rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | Drug: Rimegepant<br>* Rimegepant capsules<br>Drug: Placebo<br>* Rimegepant placebo-matching capsules<br>|
| Experimental: Treatment F: Rimegepant, 600 mg<br>Participants received a single dose (four capsules of 150 mg each) of rimegepant 600 mg orally; anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | Drug: Rimegepant<br>* Rimegepant capsules<br>Drug: Placebo<br>* Rimegepant placebo-matching capsules<br>|
| Placebo Comparator: Treatment P: Rimegepant Placebo-Matching Capsules<br>Participants received a single dose (4 capsules) of rimegepant placebo-matching capsules orally, anytime within 45 days of randomization once they experienced a migraine headache of moderate to severe intensity. | Drug: Placebo<br>* Rimegepant placebo-matching capsules<br>|
| Active Comparator: Treatment G: Sumatriptan 100 mg<br>Participants received a single dose (one capsule) of rimegepant-matching sumatriptan 100 mg orally and three rimegepant matching placebo capsules orally, anytime within 45 days of randomization once they experienced a migraine headache of moderate to severe intensity. | Drug: Placebo<br>* Rimegepant placebo-matching capsules<br>Drug: Sumatriptan<br>* Rimegepant matching sumatriptan and Rimegepant matching placebo capsules<br>* Other names: Imitrex®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | Pain freedom was defined as participants reporting a value of none on the four-point numeric rating scale (none=0, mild =1, moderate =2, severe =3) from baseline. Participants with baseline moderate pain or severe pain were included in the analysis. | Baseline, 2 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | Total migraine freedom is defined as complete absence of migraine symptoms. A participant was positive for total migraine freedom at a particular time point if he/she reports the absence of: pain, nausea, photophobia, and phonophobia. This corresponds to reporting none on each of the four-point numeric rating scale (none =0, mild =1, moderate =2, severe =3) from baseline associated with these symptoms. Participants with baseline moderate pain or severe pain were included in the analysis. | Baseline, 2 hours post dose | 
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. | AEs: from first dose to end of treatment visit (up to 7 weeks); SAE: from signing of informed consent to 30 days after the last dose (up to 11 weeks). | 
| Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | Participants were considered to have sustained pain freedom if all of their reported pain readings in the interval are none on the four point numeric rating scale (no pain=0, mild pain=1, moderate pain=2, severe pain=3). The intervals are inclusive of the endpoints. Sustained pain freedom was analyzed with a Cochran Mantel Haenszel (CMH) test for general association that compares the ED90 to placebo, and controls for baseline pain severity. | 2 hours to 24 hours post dose | 
| Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | Participants were considered to have sustained pain freedom if all of their reported pain readings in the interval are none on the four point numeric rating scale (no pain=0, mild pain=1, moderate pain=2, severe pain=3). The intervals are inclusive of the endpoints. Sustained pain freedom was analyzed with a CMH test for general association that compares the ED90 to placebo, and controls for baseline pain severity. | 2 hours to 48 hours post dose |