Efficacy and Safety Trial of Rimegepant for Migraine Prevention in Adults

NCT03732638 | Completed Phase 2 Results FDA Drug

• 1 other identifier: BHV3000-305
• Study Type: interventional
• Target: 1,590
• Locations: 1 country
• Sites: 93

Brief Summary

The purpose of this is study is to compare the efficacy of BHV-3000 (rimegepant) to placebo as a preventive treatment for migraine, as measured by the reduction in the number of migraine days per month.

Conditions

Migraine

Keywords

Migraine; Prevention; Prophylaxis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Mean Number of Total Migraine Days Per Month in the Last 4 Weeks of the DBT Phase

  A migraine day: any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache: a migraine with or without aura, lasting for ≥30 minutes, and meeting at least 1 of the following criteria (a and/or b): a) ≥2 of the following: unilateral location, pulsating quality, moderate to severe pain intensity, aggravation by or causing avoidance of routine physical activity; b) ≥1 of the following: nausea and/or vomiting, photophobia, and phonophobia. If the participant took a migraine-specific medication during aura or to treat headache on a calendar day, it was counted as a migraine day regardless of the duration and pain features/associated symptoms. Months were defined as 28-day intervals. The change from baseline was calculated as the number of monthly migraine days during the last 4 weeks of the DBT phase (Weeks 9 to 12) minus number of monthly migraine days during the OP.

  OP and Weeks 9 to 12 of the DBT phase

Secondary Outcomes (14)

• Number of Participants Who Had ≥ 50% Reduction in Moderate or Severe Migraine Days Per Month in the Last 4 Weeks of the DBT Phase

  OP and Weeks 9 to 12 of the DBT phase

• Change From Baseline in the Mean Number of Migraine Days Per Month Over the Entire Course of the DBT Phase

  OP and Weeks 1 to 12 of the DBT phase

• Frequency of Use of Rescue Medication Days Per Month in the Last Month of the DBT Phase

  Weeks 9 to 12 of the DBT phase

• Change From Baseline in the Mean Number of Total Migraine Days Per Month in the First Month of the DBT Phase

  OP and Weeks 1 to 4 of the DBT phase

• Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Study Drug Discontinuation in the DBT Phase

  Weeks 1 to 12 of the DBT phase

Study Arms (2)

DBT Rimegepant/OL Rimegepant

EXPERIMENTAL

DBT Phase (Weeks 1 through 12): Participants received a single oral dose of rimegepant 75 mg tablet every other day (EOD) for 12 weeks. OLE Phase (Weeks 13 through 64): Participants who continued to meet study entry criteria and had acceptable laboratory test results per protocol, entered the OLE phase and received a single oral dose of rimegepant 75 mg tablet EOD for 52 weeks. If participants had a migraine on a day that they were not scheduled to dose with rimegepant, they could take one tablet of rimegepant 75 mg on that calendar day to treat a migraine (as needed \[PRN\] dosing). After completing the OLE phase, participants had follow-up safety visits 2 and 8 weeks after the End-of-Treatment (EOT) visit. Participants who did not complete the DBT phase and/or did not enter or complete the OLE phase were to complete the EOT visit, the 2-week follow-up safety visit, and the 8-week follow-up safety visit after their early discontinuation.

Drug: Rimegepant

DBT Placebo/OL Rimegepant

PLACEBO COMPARATOR

DBT Phase (Weeks 1 through 12): Participants received a single oral dose of placebo matching to rimegepant tablet EOD for 12 weeks. OLE Phase (Weeks 13 through 64): Participants who continued to meet study entry criteria and had acceptable laboratory test results per protocol, entered the OLE phase and received a single oral dose of rimegepant 75 mg tablet EOD for 52 weeks. If participants had a migraine on a day that they were not scheduled to dose with rimegepant, they could take one tablet of rimegepant 75 mg on that calendar day to treat a migraine (PRN dosing). After completing the OLE phase, participants had follow-up safety visits 2 and 8 weeks after the End-of-Treatment (EOT) visit. Participants who did not complete the DBT phase and/or did not enter or complete the OLE phase were to complete the EOT visit, the 2-week follow-up safety visit, and the 8-week follow-up safety visit after their early discontinuation.

Drug: Rimegepant; Drug: Placebo

Interventions

Rimegepant DRUG

Rimegepant 75 mg tablet EOD

Also known as: BHV-3000

DBT Placebo/OL Rimegepant; DBT Rimegepant/OL Rimegepant

Placebo DRUG

Placebo tablet to match rimegepant tablet EOD

DBT Placebo/OL Rimegepant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has at least 1 year history of migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following:
• Age of onset of migraines prior to 50 years of age
• Migraine attacks, on average, lasting 4 - 72 hours if untreated
• Per subject report, 4 - 18 migraine attacks of moderate to severe intensity per month within the last 3 months prior to the Screening Visit
• or more migraine days during the Observation Period
• Not more than 18 headache days during the Observation Period
• Ability to distinguish migraine attacks from tension/cluster headaches
• Subjects on prophylactic migraine medication are permitted to remain on 1 medication with possible migraine-prophylactic effects if the dose has been stable for at least 3 months prior to the Screening Visit, and the dose is not expected to change during the course of the study.

You may not qualify if:

• Subject with a history of HIV disease
• 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
• 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 screening).
• Subjects with major depressive episode within the last 12 months, major depressive disorder or any anxiety disorder requiring more than 1 medication for each disorder. Medications to treat major depressive disorder or an anxiety disorder must have been at a stable dose for at least 3 months prior to the Screening visit.
• Subjects with other pain syndromes, psychiatric conditions, dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments
• 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
• Body mass index ≥ 33 kg/m2
• Subject has current diagnosis of major depressive disorder requiring treatment with atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder
• History of gallstones or cholecystectomy.
• The subject has a history or current evidence of any unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known or 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (93)

MDFirst Research-Chandler

Chandler, Arizona, 85286, United States

Location

MedPharmics, LLC

Phoenix, Arizona, 85015, United States

Location

Tucson Neuroscience Research

Tucson, Arizona, 85710, United States

Location

Baptist Health Center for Clinical Research

Little Rock, Arkansas, 72205, United States

Location

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

Axiom Research, LLC

Apple Valley, California, 92307, United States

Location

Axiom Research, LLC

Colton, California, 92324, United States

Location

eStudySite

La Mesa, California, 91942, United States

Location

Synergy San Diego

Lemon Grove, California, 91945, United States

Location

Collaborative Neuroscience Network, LLC

Long Beach, California, 90806, United States

Location

Pacific Research Partners, LLC

Oakland, California, 94607, United States

Location

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

Optimus Medical Group

San Francisco, California, 94102, United States

Location

Artemis Institute for Clinical Research

San Marcos, California, 92078, United States

Location

Neurological Research Institute

Santa Monica, California, 90404, United States

Location

California Neuroscience Research Medical Group

Sherman Oaks, California, 91403, United States

Location

Ki Health Partners, LLC, dba New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Galiz Research

Hialeah, Florida, 33016, United States

Location

Multi-Specialty Research Associates, Inc.

Lake City, Florida, 32055, United States

Location

Qps Mra, Llc

Miami, Florida, 33143, United States

Location

AppleMed Research Group, LLC

Miami, Florida, 33155, United States

Location

Harmony Clinical Research

North Miami Beach, Florida, 33162, United States

Location

Ormond Medical Arts Pharmaceutical Research Center

Ormond Beach, Florida, 32174, United States

Location

JSV Clinical Research Study Inc.

Tampa, Florida, 33634, United States

Location

Premiere Research Institute

West Palm Beach, Florida, 33407, United States

Location

iResearch Atlanta, LLC

Decatur, Georgia, 30030, United States

Location

Northwest Clinical Trials, Inc

Boise, Idaho, 83704, United States

Location

R&R Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

Cedar Crosse Research Center

Chicago, Illinois, 60607, United States

Location

Family Medicine Specialists/CIS

Wauconda, Illinois, 60084, United States

Location

Community Clinical Research Center

Anderson, Indiana, 46011, United States

Location

Heartland Research Associates, LLC

Newton, Kansas, 67114, United States

Location

Phoenix Medical Research

Prairie Village, Kansas, 66208, United States

Location

Heartland Research Associates, LLC

Wichita, Kansas, 67207, United States

Location

Crescent City Headache and Neurology Center

Chalmette, Louisiana, 70043, United States

Location

New Orleans Center for Clinical Research

New Orleans, Louisiana, 70119, United States

Location

DelRicht Research

New Orleans, Louisiana, 70124, United States

Location

Boston Clinical Trials

Boston, Massachusetts, 02131, United States

Location

ActivMed Practices & Research, Inc.

Methuen, Massachusetts, 01844, United States

Location

Regeneris Medical

North Attleboro, Massachusetts, 02760, United States

Location

Michigan Head Pain & Neurological Institute

Ann Arbor, Michigan, 48104, United States

Location

Michigan Pain Consultants

Grand Rapids, Michigan, 49503, United States

Location

MedPharmics, LLC

Biloxi, Mississippi, 39531, United States

Location

Clinical Research Professionals, Inc.

Chesterfield, Missouri, 63005, United States

Location

StudyMetrix Research

City of Saint Peters, Missouri, 63303, United States

Location

The Center for Pharmaceutical Research, LLC

Kansas City, Missouri, 64114, United States

Location

Clinvest Research LLC

Springfield, Missouri, 65810, United States

Location

Sundance Clinical Research, LLC

St Louis, Missouri, 63141, United States

Location

Meridian Clinical Research, LLC

Norfolk, Nebraska, 68701, United States

Location

Quality Clinical Research, Inc

Omaha, Nebraska, 68114, United States

Location

Nevada Headache Institute

Las Vegas, Nevada, 89113, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Albuquerque Neuroscience, Inc.

Albuquerque, New Mexico, 87109, United States

Location

Central New York Clinical Research

Manlius, New York, 13104, United States

Location

Mid Hudson Medical Research, PLLC

New Windsor, New York, 12553, United States

Location

Island Neurological, A Division of Prohealth Care Associates, LLP

Plainview, New York, 11803, United States

Location

Upstate Clinical Research Associates, LLC

Williamsville, New York, 14221, United States

Location

PharmQuest, LLC

Greensboro, North Carolina, 27408, United States

Location

PMG Research

Raleigh, North Carolina, 27609, United States

Location

Carolina Research Institute Center, Inc.

Shelby, North Carolina, 28150, United States

Location

Lillestol Research LLC

Fargo, North Dakota, 58104, United States

Location

Hometown Urgent Care

Cincinnati, Ohio, 45215, United States

Location

Hometown Urgent Care and Research

Dayton, Ohio, 45424, United States

Location

Neurology Diagnostics Research

Dayton, Ohio, 45459, United States

Location

Aventiv Research, Inc

Dublin, Ohio, 43016, United States

Location

Oklahoma Headache Center

Norman, Oklahoma, 73072, United States

Location

Tekton Research

Yukon, Oklahoma, 73099, United States

Location

Summit Research Network (Oregon) Inc.

Portland, Oregon, 97210, United States

Location

Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)

Salem, Oregon, 97301, United States

Location

Clinical Research of Philadelphia, LLC

Philadelphia, Pennsylvania, 19114, United States

Location

BTC of Lincoln, LLC

Lincoln, Rhode Island, 02865, United States

Location

OnSite Clinical Solutions

Dillon, South Carolina, 29536, United States

Location

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, 29464, United States

Location

Meridian Clinical Research

Dakota Dunes, South Dakota, 57049, United States

Location

Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

Tekton Research

Austin, Texas, 78745, United States

Location

FutureSearch Trials of Dallas, LP

Dallas, Texas, 75231, United States

Location

Ventavia Research Group, LLC

Fort Worth, Texas, 76104, United States

Location

North Texas Institute of Neurology & Headache

Frisco, Texas, 75034, United States

Location

Victorium Clinical Research

Houston, Texas, 77024, United States

Location

Texas Center for Drug Development, Inc.

Houston, Texas, 77081, United States

Location

Red Star Research, LLC

Lake Jackson, Texas, 77566, United States

Location

FMC Science

Lampasas, Texas, 76550, United States

Location

Victorium Clinical Research

San Antonio, Texas, 78230, United States

Location

DM Clinical Research

Tomball, Texas, 77375, United States

Location

Wasatch Clinical Research, LLC

Salt Lake City, Utah, 84107, United States

Location

Charlottesville Medical Research

Charlottesville, Virginia, 22911, United States

Location

MedStar Georgetown Headache - Georgetown University

McLean, Virginia, 22102, United States

Location

Tidewater Integrated Medical Research

Virginia Beach, Virginia, 23454, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Seattle Women's

Seattle, Washington, 98105, United States

Location

Clinical Investigation Specialists, Inc.

Kenosha, Wisconsin, 53144, United States

Location

Related Publications (4)

• Kudrow D, Croop RS, Thiry A, Lipton RB. A 52-week open-label extension study to evaluate the safety and efficacy of oral rimegepant for the preventive treatment of migraine. Headache. 2025 Jun 30. doi: 10.1111/head.15002. Online ahead of print.

  PMID: 40583813 DERIVED

• Mahon R, Tiwari S, Koch M, Ferraris M, Betts KA, Wang Y, Gao S, Proot P. Comparative effectiveness of erenumab versus rimegepant for migraine prevention using matching-adjusted indirect comparison. J Comp Eff Res. 2024 Mar;13(3):e230122. doi: 10.57264/cer-2023-0122. Epub 2024 Jan 4.

  PMID: 38174577 DERIVED

• Powell LC, L'Italien G, Popoff E, Johnston K, O'Sullivan F, Harris L, Croop R, Coric V, Lipton RB. Health State Utility Mapping of Rimegepant for the Preventive Treatment of Migraine: Double-Blind Treatment Phase and Open Label Extension (BHV3000-305). Adv Ther. 2023 Feb;40(2):585-600. doi: 10.1007/s12325-022-02369-x. Epub 2022 Nov 22.

  PMID: 36417057 DERIVED

• Croop R, Lipton RB, Kudrow D, Stock DA, Kamen L, Conway CM, Stock EG, Coric V, Goadsby PJ. Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Lancet. 2021 Jan 2;397(10268):51-60. doi: 10.1016/S0140-6736(20)32544-7. Epub 2020 Dec 15.

  PMID: 33338437 DERIVED

MeSH Terms

Conditions

Migraine Disorders

Interventions

rimegepant sulfate

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Biohaven Pharmaceuticals, Inc.

clinicaltrials@biohavenpharma.com

203-404-0410

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2018
• First Posted: November 6, 2018
• Study Start: November 14, 2018
• Primary Completion: December 10, 2019
• Study Completion: February 2, 2021
• Last Updated: June 7, 2024
• Results First Posted: August 9, 2021

Record last verified: 2022-12

Locations

US (93)