Trial in Adult Subjects With Acute Migraines

BHV3000-303: Phase 3, Double-Blind, Randomized, Placebo Controlled, Safety and Efficacy Trial of BHV-3000 (Rimegepant) Orally Disintegrating Tablet (ODT) for the Acute Treatment of Migraine

The purpose of this study is to compare the efficacy of BHV-3000 (rimegepant ODT) versus placebo in subjects with Acute Migraines.

Study Overview

• Status: Completed
• Conditions: Migraine, With or Without Aura
• Intervention / Treatment: Drug: Rimegepant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1811
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, LLC
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Clinical Research Consortium, an AMR company
    • Tucson, Arizona, United States, 85712
      • Radiant Research, Inc.
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group, LLC
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center For Clinical Research
  • California
    • Encino, California, United States, 91316
      • Pharmacology Research Institute
    • La Mesa, California, United States, 91942
      • eStudySite
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, LLC
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Institute
    • National City, California, United States, 91950
      • Synergy San Diego
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • San Francisco, California, United States, 94102
      • Optimus Medical Group
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University
    • Stamford, Connecticut, United States, 06905
      • Ki Health Partners LLC DBA New England Institute for Clinical Research
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Hialeah, Florida, United States, 33012
      • Aga Clinical Trials
    • Lake City, Florida, United States, 32055
      • Multi-Specialty Research Associates, Inc.
    • Miami, Florida, United States, 33143
      • Qps Mra, Llc
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc
    • Ormond Beach, Florida, United States, 32174
      • Ormond Medical Arts Pharmaceutical Research
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Synexus
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta, LLC
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research, LLC
  • Kansas
    • Augusta, Kansas, United States, 67010
      • Heartland Research Associates LLC
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates, LLC
  • Louisiana
    • Chalmette, Louisiana, United States, 70043
      • Cresent City Headache and Neurology Center LLC
    • New Orleans, Louisiana, United States, 70119
      • New Orleans Center for Clinical Research
    • New Orleans, Louisiana, United States, 70124
      • DelRicht Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Fall River, Massachusetts, United States, 02721
      • NECCR Primacare Research, LLC
    • Marlborough, Massachusetts, United States, 01752
      • Community Clinical Research Network/Milford Emergency Associates, Inc
  • Minnesota
    • Minneapolis, Minnesota, United States, 55042
      • Clinical Research Institute, Inc.
    • Plymouth, Minnesota, United States, 55441
      • Clinical Research Institute, Inc.
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Center For Pharmaceutical Research
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research, LLC
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research, LLC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
  • New York
    • Brooklyn, New York, United States, 11235
      • SPRI Clinical Trials, LLC
    • Jamaica, New York, United States, 11432
      • CNS Research Science, Inc.
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest, LLC
    • Raleigh, North Carolina, United States, 27609
      • PMG Research of Raleigh
    • Wilmington, North Carolina, United States, 28401
      • Wilmington Health, PLLC
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Radiant Research, Inc.
    • Dayton, Ohio, United States, 45424
      • Hometown Urgent Care and Research
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics, Inc.
    • Dublin, Ohio, United States, 43016
      • Aventiv Research Inc
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network (Oregon) Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research Of Philadelphia, Llc
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
      • Meridian Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
    • Nashville, Tennessee, United States, 37203
      • Nashville Neuroscience Group
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Institute, Inc.
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Fort Worth, Texas, United States, 76104
      • Ventavia Research Group, LLC
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Lake Jackson, Texas, United States, 77566
      • Red Star Research
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Virginia Beach, Virginia, United States, 23454
      • Tidewater Integrated Medical Research
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98105
      • Seattle Women's: Health, Research, Gynecology
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53144
      • Clinical Investigation Specialists, Inc.

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Subject has at least 1 year history of migraines (with or without aura), consistent with a diagnosis according to the International Classification of Headache Disorder, 3rd Edition, Beta version [1] including the following:

1. Migraine attacks present for more than 1 year with the age of onset prior to 50 years of age
2. Migraine attacks, on average, lasting about 4-72 hours if untreated
3. Not more than 8 attacks of moderate to severe intensity per month within the last 3 months
4. Consistent migraine headaches of at least 2 migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening period
5. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening Period.
6. Subjects on prophylactic migraine medication are permitted to remain on therapy provided they have been on a stable dose for at least 3 months prior to screening visit and the dose is not expected to change during the course of the study.
7. Subjects with contraindications for use of triptans may be included provided they meet all other study entry criteria.

Key Exclusion Criteria:

1. Subject with a history of HIV disease
2. Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening
3. Uncontrolled hypertension (high blood pressure), or uncontrolled diabetes (however subjects can be included who have stable hypertension and/or diabetes for at least 3 months prior to being enrolled)
4. Subject has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (e.g., schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion might interfere with study assessments.
5. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease that causes malabsorption
6. The subject has a history of current or evidence of any significant and/ or unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial.
7. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or subjects who have met DSM-V criteria for any significant substance use disorder within the past 12 months from the date of the screening visit.
8. Subjects are excluded if they have previously participated in any BHV-30000 (rimegepant) study within the last 2 years.
9. Participation in any other investigational clinical trial while participating in this clinical trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Rimegepant 75 mg; Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Drug: Rimegepant; 75 mg ODT QD; Other Names: BHV-3000
Placebo Comparator: Arm 2: Placebo; Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Drug: Placebo; Placebo ODT to match rimegepant dose QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Freedom From Pain at 2 Hours Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic diary (eDiary). Pain freedom was defined as pain level of none.	2 hours post-dose
Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose	MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at onset that was absent post-dose.	2 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose	Photophobia (sensitivity to light) status was measured as absent or present in the eDiary. Freedom from photophobia was defined as photophobia absent.	2 hours post-dose
Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose	Phonophobia (sensitivity to sound) status was measured as absent or present in the eDiary. Freedom from phonophobia was defined as phonophobia absent.	2 hours post-dose
Percentage of Participants With Pain Relief at 2 Hours Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild.	2 hours post-dose
Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose	Nausea status was measured as absent or present in the eDiary. Freedom from nausea was defined as nausea absent.	2 hours post-dose
Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose	Participants who did not experience relief of their migraine headache at the end of 2 hours after dosing with study medication (and after the 2-hour assessments had been completed on the eDiary) were permitted to use the following rescue medications: aspirin, ibuprofen, acetaminophen up to 1000 mg/day (this includes Excedrin Migraine), naproxen (or any other type of nonsteroidal anti-inflammatory drug), antiemetics (e.g., metoclopramide or promethazine), or baclofen. The participant's use of rescue medication was recorded by the participant in a paper diary.	24 hours post-dose
Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.	From 2 hours up to 24 hours post-dose
Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.	From 2 hours up to 24 hours post-dose
Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.	From 2 hours up to 48 hours post-dose
Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.	From 2 hours up to 48 hours post-dose
Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose	Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function.	2 hours post-dose
Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 24 Hours Post-dose	MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Sustained freedom was defined as MBS reported at onset that was absent at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.	From 2 hours up to 24 hours post-dose
Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 24 Hours Post-dose	Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Sustained freedom from functional disability was defined as normal function at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.	From 2 hours up to 24 hours post-dose
Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 48 Hours Post-dose	MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Sustained freedom was defined as MBS reported at onset that was absent at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.	From 2 hours up to 48 hours post-dose
Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 48 Hours Post-dose	Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Sustained freedom from functional disability was defined as normal function at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.	From 2 hours up to 48 hours post-dose
Percentage of Participants With Freedom From Functional Disability at 90 Minutes Post-dose	Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function.	90 minutes post-dose
Percentage of Participants With Pain Relief at 90 Minutes Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild.	90 minutes post-dose
Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 90 Minutes Post-dose	MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at onset that was absent post-dose.	90 minutes post dose
Percentage of Participants With Freedom From Pain at 90 Minutes Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic diary (eDiary). Pain freedom was defined as pain level of none.	90 minutes post-dose
Percentage of Participants With Pain Relief at 60 Minutes Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild.	60 minutes post-dose
Percentage of Participants With Freedom From Functional Disability at 60 Minutes Post-dose	Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function.	60 minutes post-dose
Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relapse was defined as pain level of mild, moderate, or severe after 2 hours up to 48 hours post-dose for the participants who were pain-free at 2 hours post-dose.	From 2 hours up to 48 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Johnston KM, Powell L, Popoff E, Harris L, Croop R, Coric V, L'Italien G. Rimegepant, Ubrogepant, and Lasmiditan in the Acute Treatment of Migraine Examining the Benefit-Risk Profile Using Number Needed to Treat/Harm. Clin J Pain. 2022 Nov 1;38(11):680-685. doi: 10.1097/AJP.0000000000001072.
• Croop R, Goadsby PJ, Stock DA, Conway CM, Forshaw M, Stock EG, Coric V, Lipton RB. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019 Aug 31;394(10200):737-745. doi: 10.1016/S0140-6736(19)31606-X. Epub 2019 Jul 13.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2018
• Primary Completion (Actual): October 8, 2018
• Study Completion (Actual): October 15, 2018

Study Registration Dates

• First Submitted: March 6, 2018
• First Submitted That Met QC Criteria: March 9, 2018
• First Posted (Actual): March 12, 2018

Study Record Updates

• Last Update Posted (Actual): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 14, 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
• Other Study ID Numbers: BHV3000-303

Drug and device information, study documents

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