Trial in Adult Subjects With Acute Migraines

• ClinicalTrials.gov Identifier: NCT03461757
• Recruitment Status: Completed
• First Posted: March 12, 2018
• Results First Posted: March 27, 2020
• Last Update Posted: February 16, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Migraine, With or Without Aura	Drug: Rimegepant; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1811 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized Controlled Trial
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-blind to Sponsor, Investigator and Participant
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 27, 2018
• Actual Primary Completion Date: October 8, 2018
• Actual Study Completion Date: October 15, 2018

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Freedom From Pain at 2 Hours Post-dose [ Time Frame: 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. Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose [ Time Frame: 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.

Secondary Outcome Measures :

1. Percentage of Participants With Pain Relief at 2 Hours Post-dose [ Time Frame: 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. Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose [ Time Frame: 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.
3. Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose [ Time Frame: From 2 hours up 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.
4. Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 24 Hours Post-dose [ Time Frame: From 2 hours up 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.
5. Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose [ Time Frame: 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.
6. Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 24 Hours Post-dose [ Time Frame: From 2 hours up 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.
7. Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up 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.
8. Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up 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.
9. Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up 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.
10. Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose [ Time Frame: 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.
11. Percentage of Participants With Freedom From Functional Disability at 90 Minutes Post-dose [ Time Frame: 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.
12. Percentage of Participants With Pain Relief at 90 Minutes Post-dose [ Time Frame: 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.
13. Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose [ Time Frame: From 2 hours up 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.
14. Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 90 Minutes Post-dose [ Time Frame: 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.
15. Percentage of Participants With Freedom From Pain at 90 Minutes Post-dose [ Time Frame: 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.
16. Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose [ Time Frame: 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.
17. Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up 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.
18. Percentage of Participants With Pain Relief at 60 Minutes Post-dose [ Time Frame: 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.
19. Percentage of Participants With Freedom From Functional Disability at 60 Minutes Post-dose [ Time Frame: 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.
20. Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Nausea status was measured as absent or present in the eDiary. Freedom from nausea was defined as nausea absent.
21. Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose [ Time Frame: From 2 hours up 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Coastal Clinical Research, LLC

Mobile, Alabama, United States, 36608

United States, Arizona

Clinical Research Consortium, An AMR Company

Tempe, Arizona, United States, 85283

Radiant Research, Inc.

Tucson, Arizona, United States, 85712

United States, Arkansas

Baptist Health Center for Clinical Research

Little Rock, Arkansas, United States, 72205

Woodland International Research Group, LLC

Little Rock, Arkansas, United States, 72211

United States, California

Pharmacology Research Institute

Encino, California, United States, 91316

eStudySite

La Mesa, California, United States, 91942

Collaborative Neuroscience Network, LLC

Long Beach, California, United States, 90806

Pharmacology Research Institute

Los Alamitos, California, United States, 90720

Synergy San Diego

National City, California, United States, 91950

Pharmacology Research Institute

Newport Beach, California, United States, 92660

Optimus Medical Group

San Francisco, California, United States, 94102

Diablo Clinical Research, Inc.

Walnut Creek, California, United States, 94598

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06519

Ki Health Partners LLC DBA New England Institute for Clinical Research

Stamford, Connecticut, United States, 06905

United States, Florida

MD Clinical

Hallandale Beach, Florida, United States, 33009

AGA Clinical Trials

Hialeah, Florida, United States, 33012

Multi-Specialty Research Associates, Inc.

Lake City, Florida, United States, 32055

Qps Mra, Llc

Miami, Florida, United States, 33143

Clinical Neuroscience Solutions, Inc

Orlando, Florida, United States, 32801

Ormond Medical Arts Pharmaceutical Research

Ormond Beach, Florida, United States, 32174

United States, Georgia

Synexus

Atlanta, Georgia, United States, 30328

iResearch Atlanta, LLC

Decatur, Georgia, United States, 30030

Meridian Clinical Research, LLC

Savannah, Georgia, United States, 31406

United States, Kansas

Heartland Research Associates LLC

Augusta, Kansas, United States, 67010

Heartland Research Associates, LLC

Wichita, Kansas, United States, 67205

United States, Louisiana

Cresent City Headache and Neurology Center LLC

Chalmette, Louisiana, United States, 70043

New Orleans Center for Clinical Research

New Orleans, Louisiana, United States, 70119

DelRicht Research

New Orleans, Louisiana, United States, 70124

United States, Massachusetts

Boston Clinical Trials

Boston, Massachusetts, United States, 02131

NECCR Primacare Research, LLC

Fall River, Massachusetts, United States, 02721

Community Clinical Research Network/Milford Emergency Associates, Inc

Marlborough, Massachusetts, United States, 01752

United States, Minnesota

Clinical Research Institute, Inc.

Minneapolis, Minnesota, United States, 55042

Clinical Research Institute, Inc.

Plymouth, Minnesota, United States, 55441

United States, Missouri

Center for Pharmaceutical Research

Kansas City, Missouri, United States, 64114

Sundance Clinical Research

Saint Louis, Missouri, United States, 63141

StudyMetrix Research, LLC

Saint Peters, Missouri, United States, 63303

United States, Nebraska

Meridian Clinical Research, LLC

Norfolk, Nebraska, United States, 68701

United States, New Jersey

Hassman Research Institute

Berlin, New Jersey, United States, 08009

United States, New Mexico

Albuquerque Clinical Trials, Inc.

Albuquerque, New Mexico, United States, 87102

United States, New York

SPRI Clinical Trials, LLC

Brooklyn, New York, United States, 11235

CNS Research Science, Inc.

Jamaica, New York, United States, 11432

Rochester Clinical Research, Inc.

Rochester, New York, United States, 14609

United States, North Carolina

PharmQuest, LLC

Greensboro, North Carolina, United States, 27408

PMG Research of Raleigh

Raleigh, North Carolina, United States, 27609

Wilmington Health, PLLC

Wilmington, North Carolina, United States, 28401

United States, Ohio

Radiant Research, Inc.

Columbus, Ohio, United States, 43212

Midwest Clinical Research Center

Dayton, Ohio, United States, 45417

Hometown Urgent Care and Research

Dayton, Ohio, United States, 45424

Neurology Diagnostics, Inc.

Dayton, Ohio, United States, 45459

Aventiv Research Inc

Dublin, Ohio, United States, 43016

United States, Oregon

Summit Research Network (Oregon) Inc.

Portland, Oregon, United States, 97210

United States, Pennsylvania

Clinical Research of Philadelphia, LLC

Philadelphia, Pennsylvania, United States, 19114

United States, South Carolina

Coastal Carolina Research

Mount Pleasant, South Carolina, United States, 29464

United States, South Dakota

Meridian Clinical Research

Dakota Dunes, South Dakota, United States, 57049

United States, Tennessee

Volunteer Research Group

Knoxville, Tennessee, United States, 37920

Clinical Research Institute, Inc.

Nashville, Tennessee, United States, 37203

Nashville Neuroscience Group

Nashville, Tennessee, United States, 37203

United States, Texas

Tekton Research, Inc

Austin, Texas, United States, 78745

FutureSearch Trials of Dallas, LP

Dallas, Texas, United States, 75231

Ventavia Research Group, LLC

Fort Worth, Texas, United States, 76104

Texas Center for Drug Development, Inc.

Houston, Texas, United States, 77081

Red Star Research

Lake Jackson, Texas, United States, 77566

DM Clinical Research

Tomball, Texas, United States, 77375

United States, Virginia

Charlottesville Medical Research

Charlottesville, Virginia, United States, 22911

Tidewater Integrated Medical Research

Virginia Beach, Virginia, United States, 23454

United States, Washington

Northwest Clinical Research Center

Bellevue, Washington, United States, 98007

Seattle Women's: Health, Research, Gynecology

Seattle, Washington, United States, 98105

United States, Wisconsin

Clinical Investigation Specialists, Inc.

Kenosha, Wisconsin, United States, 53144

Sponsors and Collaborators

Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] July 23, 2018

Statistical Analysis Plan  [PDF] November 15, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03461757
• Other Study ID Numbers: BHV3000-303
• First Posted: March 12, 2018
• Results First Posted: March 27, 2020
• Last Update Posted: February 16, 2023
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases