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

Phase 2

Completed

Conditions: Migraine
Acute Treatment of Migraine

Interventions: Drug: Rimegepant
Drug: Placebo
Drug: Sumatriptan

Registration Number: NCT01430442

Lead Sponsor: Pfizer

Brief Summary: 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: Intervention Model: Parallel Versus Comparator + Placebo

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1026

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment D: Rimegepant, 150 mg	Rimegepant	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.
Treatment A: Rimegepant, 10 mg	Placebo	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.
Treatment B: Rimegepant, 25 mg	Placebo	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.
Treatment C: Rimegepant, 75 mg	Rimegepant	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.
Treatment C: Rimegepant, 75 mg	Placebo	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.
Treatment D: Rimegepant, 150 mg	Placebo	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.
Treatment E: Rimegepant, 300 mg	Placebo	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.
Treatment F: Rimegepant, 600 mg	Placebo	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.
Treatment P: Rimegepant Placebo-Matching Capsules	Placebo	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.
Treatment G: Sumatriptan 100 mg	Placebo	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.
Treatment G: Sumatriptan 100 mg	Sumatriptan	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.
Treatment A: Rimegepant, 10 mg	Rimegepant	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.
Treatment B: Rimegepant, 25 mg	Rimegepant	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.
Treatment E: Rimegepant, 300 mg	Rimegepant	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.
Treatment F: Rimegepant, 600 mg	Rimegepant	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.

Primary Outcome Measures

Name	Time	Method
Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Total Migraine Freedom at 2 Hours Post Dose	Baseline, 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.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events	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).	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.
Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose	2 hours 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.
Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose	2 hours 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.

Trial Locations

Locations (40): Broward Research Group
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Pembroke Pines, Florida, United States
Clinical Res. Advantage Inc/ Desert Clinical Research Llc
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Tempe, Arizona, United States
Tidewater Integrated Medical Research
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Virginia Beach, Virginia, United States
Diablo Clinical Research, Inc.
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Walnut Creek, California, United States
Pharmquest
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Greensboro, North Carolina, United States
Clinical Research Of Philadelphia, Llc
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Philadelphia, Pennsylvania, United States
Milford Emergency Associates, Inc.
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Milford, Massachusetts, United States
Medvadis Research Corporation
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Watertown, Massachusetts, United States
Clinvest/ A Division Of Banyan Group, Inc.
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Springfield, Missouri, United States
Renstar Medical Research
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Ocala, Florida, United States
Central New York Clinical Research
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Manlius, New York, United States
The Innovative Clinical Research Center
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Alexandria, Virginia, United States
Diamond Headache Clinic, Ltd.
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Chicago, Illinois, United States
Cleveland Clinic
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Cleveland, Ohio, United States
Miami Research Associates
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Miami, Florida, United States
University Of California, San Francisco
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San Francisco, California, United States
Community Research
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Cincinnati, Ohio, United States
J. Lewis Research, Inc
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Salt Lake City, Utah, United States
Swedish Pain And Headache Center
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Seattle, Washington, United States
Mayo Clinic Arizona
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Scottsdale, Arizona, United States
California Medical Clinic For Headache
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Santa Monica, California, United States
Encompass Clinical Research
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Spring Valley, California, United States
Comprehensive Clinical Development, Inc
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Saint Petersburg, Florida, United States
Clinical Research Institute, Inc.
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Minneapolis, Minnesota, United States
Regional Clinical Research Inc.
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Endwell, New York, United States
Rochester Clinical Research, Inc.
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Rochester, New York, United States
Clinsearch, Llc
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Chattanooga, Tennessee, United States
Omega Medical Research
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Warwick, Rhode Island, United States
Premier Research Group Limited
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Austin, Texas, United States
Coastal Carolina Research Center, Inc.
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Mount Pleasant, South Carolina, United States
Wake Research Associates
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Raleigh, North Carolina, United States
Mercy Health Research
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Saint Louis, Missouri, United States
Futuresearch Trials Of Neurology
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Austin, Texas, United States
R/D Clinical Research, Inc.
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Lake Jackson, Texas, United States
Compass Research, Llc
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Orlando, Florida, United States
Radiant Research, Inc.
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Denver, Colorado, United States
Michigan Head Pain And Neurological Institute
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Ann Arbor, Michigan, United States
The Center For Pharmaceutical Research. Pc
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Kansas City, Missouri, United States
Pmg Research Of Winston-Salem
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Winston-Salem, North Carolina, United States
Thomas Jefferson University
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Philadelphia, Pennsylvania, United States