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

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

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.

Study Overview

• Status: Completed
• Conditions: Migraine; Acute Treatment of Migraine
• Intervention / Treatment: Drug: Rimegepant; Drug: Placebo; Drug: Sumatriptan

Detailed Description

Intervention Model: Parallel Versus Comparator + Placebo

• Study Type: Interventional
• Enrollment (Actual): 1026
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
    • Tempe, Arizona, United States, 85282
      • Clinical Res. Advantage Inc/ Desert Clinical Research Llc
  • California
    • San Francisco, California, United States, 94115
      • University of California, San Francisco
    • Santa Monica, California, United States, 90404
      • California Medical Clinic for Headache
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Colorado
    • Denver, Colorado, United States, 80239
      • Radiant Research, Inc.
  • Florida
    • Miami, Florida, United States, 33143
      • Miami Research Associates
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Pembroke Pines, Florida, United States, 33026
      • Broward Research Group
    • Saint Petersburg, Florida, United States, 33716
      • Comprehensive Clinical Development, Inc
  • Illinois
    • Chicago, Illinois, United States, 60642
      • Diamond Headache Clinic, Ltd.
  • Massachusetts
    • Milford, Massachusetts, United States, 01757
      • Milford Emergency Associates, Inc.
    • Watertown, Massachusetts, United States, 02472-3930
      • MedVadis Research Corporation
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head Pain and Neurological Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute, Inc.
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center For Pharmaceutical Research. Pc
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
    • Springfield, Missouri, United States, 65807
      • Clinvest/ A Division Of Banyan Group, Inc.
  • New York
    • Endwell, New York, United States, 13760
      • Regional Clinical Research Inc.
    • Manlius, New York, United States, 13104
      • Central New York Clinical Research
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Community Research
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research of Philadelphia, LLC
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center, Inc.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • ClinSearch, LLC
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Austin, Texas, United States, 78705
      • Premier Research Group Limited
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research, Inc.
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • The Innovative Clinical Research Center
    • Virginia Beach, Virginia, United States, 23454
      • Tidewater Integrated Medical Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Pain And Headache Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: Rimegepant, 10 mg; 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; Rimegepant capsules; Drug: Placebo; Rimegepant placebo-matching capsules
Experimental: Treatment B: Rimegepant, 25 mg; 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; Rimegepant capsules; Drug: Placebo; Rimegepant placebo-matching capsules
Experimental: Treatment C: Rimegepant, 75 mg; 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; Rimegepant capsules; Drug: Placebo; Rimegepant placebo-matching capsules
Experimental: Treatment D: Rimegepant, 150 mg; 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; Rimegepant capsules; Drug: Placebo; Rimegepant placebo-matching capsules
Experimental: Treatment E: Rimegepant, 300 mg; 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; Rimegepant capsules; Drug: Placebo; Rimegepant placebo-matching capsules
Experimental: Treatment F: Rimegepant, 600 mg; 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; Rimegepant capsules; Drug: Placebo; Rimegepant placebo-matching capsules
Placebo Comparator: Treatment P: Rimegepant Placebo-Matching Capsules; 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; Rimegepant placebo-matching capsules
Active Comparator: Treatment G: Sumatriptan 100 mg; 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; Rimegepant placebo-matching capsules; Drug: Sumatriptan; Rimegepant matching sumatriptan and Rimegepant matching placebo capsules; Other Names: Imitrex®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Marcus R, Goadsby PJ, Dodick D, Stock D, Manos G, Fischer TZ. BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial. Cephalalgia. 2014 Feb;34(2):114-25. doi: 10.1177/0333102413500727. Epub 2013 Aug 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2011
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: September 7, 2011
• First Submitted That Met QC Criteria: September 7, 2011
• First Posted (Estimate): September 8, 2011

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Vasoconstrictor Agents; Sumatriptan
• Other Study ID Numbers: CN170-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No