Efficacy and Tolerability of Rimegepant for the Acute Treatment of Migraine in Adults Unsuitable for Triptan Use

BHV3000-406 (C4951004): A Phase 4, Randomized, Double-blind Placebo-Controlled, Efficacy and Tolerability Trial of Rimegepant for the Acute Treatment of Migraine in Adults Unsuitable for Triptan Use

This study is being conducted to evaluate the efficacy and tolerability of rimegepant in a population of adults that are unsuitable for triptan medications due to a previous intolerance, lack of efficacy, or contraindication (including a history of clinically-relevant cardiovascular disease).

Study Overview

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

Detailed Description

This study is being conducted to evaluate the efficacy and tolerability of rimegepant in a population of adults that are unsuitable for triptan medications due to a previous intolerance, lack of efficacy, or contraindication (including a history of clinically-relevant cardiovascular disease). Rimegepant will be further evaluated in this population with as needed use in a 12-week, open-label extension study.

• Study Type: Interventional
• Enrollment (Actual): 813
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Sippy Downs, Queensland, Australia, 4556
      • USC Clinical Trials Centre
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
• Austria
  • Carinthia
    • Klagenfurt, Carinthia, Austria, 9020
      • Klinikum Klagenfurt am Wörthersee
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medical University Innsbruck
• Belgium
  • Antwerp, Belgium, 2610
    • GZA Ziekenhuizen
  • Brussels, Belgium, 1090
    • UZ Brussel
  • Ghent, Belgium, 9000
    • UZ Gent
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis
  • Liège
    • Saint-Nicolas, Liège, Belgium, 4420
      • Cabinet Privé Dr. Simona Sava
• Canada
  • Québec, Canada, G2J 0C4
    • ALPHA Recherche Clinique
  • Alberta
    • Calgary, Alberta, Canada, T3M 1M4
      • University of Calgary South Health Campus
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and Associates Limited
  • Quebec
    • Lévis, Quebec, Canada, G6W 0M5
      • Clinique Neuro-Lévis
    • Québec, Quebec, Canada, G3K 2P8
      • ALPHA Recherche Clinique
• Denmark
  • Esbjerg, Denmark, DK-6700
    • University Hospital of Southern Denmark
  • Glostrup Municipality, Denmark, 2600
    • Danish Headache Center
  • Viborg, Denmark, DK-8800
    • Hospitalsenhed Midt
• Finland
  • Helsinki, Finland
    • Terveystalo Ruoholahti
  • Tampere, Finland, 33100
    • Terveystalo Tampere Rautatienkatu
  • Turku, Finland, 20100
    • Terveystalo Pulssi
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00830
      • Helsinki Headache Center
• France
  • Bron, France, 69500
    • Hospices Civils de Lyon - Hôpital Neurologique Pierre Wertheimer
  • Clermont-Ferrand, France, 63000
    • CHU Clermont Ferrand - Hopital Gabriel Montpied
  • Epagny Metz-Tessy, France, 74370
    • Centre Hospitalier Annecy Genevois
  • Lille, France, 59037
    • CHU de Lille - Hôpital Salengro
  • Nice, France, 06000
    • CHU Nice Hopital Cimiez
  • Paris, France, 75010
    • Hôpital Lariboisière
  • Saint-Etienne, France, 42055
    • CHU Saint-Etienne - Hôpital Nord
  • Provence
    • Marseille, Provence, France, 13005
      • Timone Hospital
• Germany
  • Berlin, Germany, 10117
    • Charité Universitätsmedizin Berlin, Neurologische Ambulanz, Kopfschmerzambulanz
  • Frankfurt, Germany, 65929
    • Kopfschmerzzentrum Frankfurt
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, D-24149
      • Neurologische Praxis Prof. Dr. Hartmut Gobel
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • University Hospital Jena
• Italy
  • Milan, Italy, 20133
    • Foundation IRCCS Neurological Institute Carlo Besta
  • Modena, Italy, 41124
    • AOU Policlinico di Modena
  • Pavia, Italy, 27100
    • Fondazione Mondino - Istituto Neurologico Nazionale IRCCS
  • Rome, Italy, 00163
    • Headache and Pain Unit - IRCCS San Raffaele
  • MI
    • Milan, MI, Italy, 20132
      • Irccs Ospedale San Raffaele
  • Naples
    • Naples, Naples, Italy, 80138
      • AOU Luigi Vanvitelli
  • RM
    • Rome, RM, Italy, 00128
      • Fondazione Policlinico Campus BioMedico
• Mexico
  • Aguascalientes, Mexico, 20116
    • Centro de Investigación Médica de Aguascalientes (CIMA)
  • Mexico City, Mexico, CDMX 06700
    • Clinstile SA de CV
  • Mexico City, Mexico, 14050
    • Operadora Unidad de Investigación En Salud de Chihuahua, Sa de Cv
  • State of Mexico
    • Tlalnepantla, State of Mexico, Mexico, 54055
      • Clinical Research Institute S.C.
• Poland
  • Katowice, Poland, 40-748
    • Vita Longa Sp. z o.o.
  • Szczecin, Poland, 70-784
    • MICS Centrum Medyczne Szczecin
  • Warsaw, Poland, 02-172
    • MTZ Clinical Research Powered by Pratia
  • Warsaw, Poland, 00-144
    • Praktyka Lekarska
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-163
      • Centrum Medyczne NEUROMED
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 52-210
      • MIGRE Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak
  • Lubusz Voivodeship
    • Nowa Sól, Lubusz Voivodeship, Poland, 67-100
      • Twoja Przychodnia Nowosolskie Centrum Medyczne
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 00-773
      • Concept Medica
    • Warsaw, Masovian Voivodeship, Poland, 02-739
      • MICS Centrum Medyczne Damiana Walbrzyska
  • Małopolska
    • Oświęcim, Małopolska, Poland, 32-600
      • Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 91-363
      • Centrum Leczenia Bolu dr n med Lukasz Kmieciak
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Seville, Spain, 41013
    • Virgen del Rocio University Hospital
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • University Hospital Marqués de Valdecilla
• Sweden
  • Lund, Sweden, 222 22
    • Skåneuro Privatmottagning
  • Stockholm, Sweden, 117 27
    • Akardo MedSite
  • Stockholm, Sweden, 112 39
    • Hälsoklustret
  • Stockholms LÄN [se-01]
    • Solna, Stockholms LÄN [se-01], Sweden, 171 64
      • CTC Solna
  • Uppsala County
    • Uppsala, Uppsala County, Sweden, 752 37
      • CTC Uppsala
• United Kingdom
  • London, United Kingdom, WC2R 2LS
    • Kings College London
  • Swinton, United Kingdom, M27 8FF
    • 4 Medical Clinical Solutions
  • Birmingham
    • Edgebaston, Birmingham, United Kingdom, B16 8LT
      • Re: Cognition Health Ltd.
  • Essex
    • Ilford, Essex, United Kingdom, IG1 4HP
      • 4 Medical Clinical Solutions London
  • Northamptonshire
    • Corby, Northamptonshire, United Kingdom, NN17 2UR
      • Lakeside Healthcare Group Research
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Clinical Research Institute
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Ki Health Partners LLC, dba New England Institute for Clinical Research
  • Florida
    • Lake City, Florida, United States, 32055
      • Wr-Msra, Llc
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare LLC
    • Ormond Beach, Florida, United States, 32174
      • Sandhill Research, LLC d/b/a Accel Research Sites Network - Ormond Clinical Research Unit
  • Georgia
    • Sandy Springs, Georgia, United States, 30328
      • WR-Mount Vernon Clinical Research, LLC
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Collective Medical Research
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Marlborough, Massachusetts, United States, 01752
      • Community Clinical Research Network Inc
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Headache & Neurological Institute
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Medical Group
    • Southfield, Michigan, United States, 48076
      • DM Clinical Research - Detroit
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Clinvest Research, LLC
    • Weldon Spring, Missouri, United States, 63304
      • St Charles Clinical Research
  • New York
    • Brooklyn, New York, United States, 11220
      • DM Clinical Research - NY, NY
    • New York, New York, United States, 10003
      • New York Neurology Associates
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center, PC
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Synexus Clinical Research US, Inc. - Anderson
  • Texas
    • Lake Jackson, Texas, United States, 77566
      • Red Star Research, LLC
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Migraine attacks present for more than 1 year with the age of onset prior to 50 years of age.
• Migraine attacks, on average, lasting about 4 - 72 hours if untreated.
• 4 to 14 migraine days per month on average across the 3 months prior to the Screening Visit (month is defined as 28 days for the purpose of this protocol).
• Less than 15 headache days (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and throughout the Screening Phase.
• Subjects must be able to distinguish migraine attacks from tension/cluster headaches.
• Subjects on prophylactic migraine medication (excluding CGRP antagonists) are permitted to remain on therapy if they have been on a stable dose for at least 3 months (12 weeks) prior to the Screening Visit, and if the dose is not expected to change during the course of the study.
• Triptan unsuitable

Exclusion Criteria:

-Target Disease Exclusion:

1. History of cluster headache, basilar migraine, or hemiplegic migraine
2. Current medication overuse headaches
3. Headaches occurring 15 or more days per month (migraine or non-migraine) in any of the 3 months prior to the Screening Visit
4. Active chronic pain syndrome (such as fibromyalgia, chronic pelvic pain, complex regional pain syndrome [CRPS])
5. Other pain syndromes (including trigeminal neuralgia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, interfere with study assessments of safety or efficacy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rimegepant; Rimegepant - Double-blind (DB) Phase: One dose of rimegepant 75 mg Oral Disintegrating Tablet (ODT) Rimegepant/Rimegepant - Open-label Extension (OLE) Phase: participants receive one dose rimegepant 75 mg ODT as needed for a qualifying acute migraine. A qualifying migraine is an attack of moderate or severe headache pain intensity. Migraine headache pain intensity will be measured on a 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe)	Drug: Rimegepant; DB Phase: Rimegepant 75 mg Orally Disintegrating Tablet (ODT); Drug: Rimegepant; OLE Phase: Rimegepant 75 mg ODT in association with each of the first 5 qualifying migraines
Placebo Comparator: Placebo; Placebo - Double-blind (DB) Phase: One dose of matching placebo Placebo/Rimegepant - Open-label Extension (OLE) Phase: participants receive one dose rimegepant 75 mg ODT for a qualifying migraine	Drug: Rimegepant; DB Phase: Rimegepant 75 mg Orally Disintegrating Tablet (ODT); Drug: Rimegepant; OLE Phase: Rimegepant 75 mg ODT in association with each of the first 5 qualifying migraines; Drug: Placebo; DB Phase: matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pain Relief at 2 Hours Post-Dose: DBT Phase	Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Pain relief at 2 hours post-dose was defined as pain intensity of none or mild at that time point.	At 2 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pain Freedom at 2 Hours Post-Dose: DBT Phase	Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Pain freedom at 2 hours post-dose was a pain intensity of none at that time point.	At 2 hours post-dose
Percentage of Participants Who Used Rescue Medications Within 24 Hours Post-Dose: DBT Phase	Post 24 hours after dosing with study medication and after the 24-hour assessments were completed on the e-diary, participants were permitted to use the following rescue medications (non-study medications) such as: 1) non-steroidal anti-inflammatory drug like acetaminophen or aspirin, ibuprofen, naproxen; 2) antiemetics like metoclopramide, promethazine; 3) other like baclofen; 4) other approved pharmacological treatment with established efficacy in the acute treatment of migraine, including locally recognized standard of care, unless otherwise specified.	Within 24 hours post-dose
Percentage of Participants With Return to Normal Function at 2 Hours Post-Dose: DBT Phase	Functional disability level was measured on a 4-point numeric rating scale (0= normal,1= mildly impaired, 2= severely impaired, 3= required bedrest). Functional disability was defined as a functional disability level of mildly impaired, severely impaired, or required bedrest. Return to normal function at 2 hours post-dose was defined as functional disability score of normal at that time point for participants with functional disability at the time of dosing.	At 2 hours post-dose
Percentage of Participants With Sustained Return to Normal Function From 2 to 24 Hours Post-Dose: DBT Phase	Functional disability level was measured on a 4-point numeric rating scale (0= normal,1= mildly impaired, 2= severely impaired, 3= required bedrest). Functional disability was defined as a functional disability level of mildly impaired, severely impaired, or required bedrest. Sustained return to normal function, from 2 to 24 hours post-dose was defined as functional disability levels of normal at all time points from 2 to 24 hours post-dose in participants with functional disability at the time of dosing.	From 2 to 24 hours post-dose
Percentage of Participants With Sustained Return to Normal Function From 2 to 48 Hours Post-Dose: DBT Phase	Functional disability level was measured on a 4-point numeric rating scale (0= normal,1= mildly impaired, 2= severely impaired, 3= required bedrest). Functional disability was defined as a functional disability level of mildly impaired, severely impaired, or required bedrest. Sustained return to normal function, from 2 to 48 hours post-dose was defined as functional disability levels of normal at all time points from 2 to 48 hours post-dose in participants with functional disability at the time of dosing.	From 2 to 48 hours post-dose
Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-Dose: DBT Phase	Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Sustained pain relief from 2 to 24 hours post-dose was defined as a pain intensity of none or mild at all time points from 2 to 24 hours post-dose.	From 2 to 24 hours post-dose
Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-Dose: DBT Phase	Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Sustained pain relief from 2 to 48 hours post-dose was defined as a pain intensity of none or mild at all time points from 2 to 48 hours post-dose.	From 2 to 48 hours post-dose
Percentage of Participants With Sustained Freedom From Pain From 2 to 24 Hours Post-Dose: DBT Phase	Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Sustained pain freedom from 2 to 24 hours post-dose was defined as a pain intensity of none at all time points from 2 to 24 hours post-dose.	From 2 to 24 hours post-dose
Percentage of Participants With Sustained Freedom From Pain From 2 to 48 Hours Post-Dose: DBT Phase	Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Sustained pain freedom from 2 to 48 hours post-dose was defined as a pain intensity of none at all time points from 2 to 48 hours post-dose.	From 2 to 48 hours post-dose
Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-Dose: DBT Phase	MBS freedom was defined as MBS reported before dosing that was absent post-dose at the specified time point. MBS reported before dosing was nausea, photophobia, or phonophobia. Each symptom (nausea, photophobia, or phonophobia) was measured post-dose using 0= absent or 1= present. Participants who had symptom score of 0 (absent) aligning with MBS reported before dosing were considered to have MBS freedom.	At 2 hours post-dose
Reliability of Rimegepant Effect in the OLE Phase Based on Evaluable Qualifying Migraine Attacks (EQMA) of DBT and OLE Phase	Reliability of rimegepant effect during OLE Phase achieved when difference between (1) percentage of participants randomized to rimegepant with response to single EQMA in DBT phase and(2) percentage of participants with response to >=4 of first 5 EQMAs >=23 hours(h) apart in OLE phase was <=7%. Statistical analysis reports difference between (1) and (2) for each first 5 EQMAs >=23h apart in OLE phase. Response: category of "moderately better" or"very much better" for Migraine Quality of Life Questionnaire(MQoL)Question(Q) 16 (overall change in migraine symptoms since taking study medication) at 24h post-dose. EQMA:evaluable qualifying migraine attack (migraine attack of moderate/severe pain intensity,first treated with rimegepant, not other acute headache medication) with nonmissing MQoL Q16 value at 24h post dose. Percentage of participants with response after single EQMA in DBT phase randomized to rimegepant and each of first 5 EQMA in OLE phase are reported in descriptive section.	DBT phase: up to maximum 45 days; OLE phase: up to maximum of 12 weeks
Mean Change From Historical Baseline in Number of Migraine Days Per Month by Headache Pain Intensity at Months 1, 2 and 3 and Overall: OLE Phase	Mean change from historical baseline in the number of migraine days per month by headache pain intensity (total; moderate or severe) at each specified month and over the entire OLE Phase is reported in this outcome measure. A migraine day was defined as either 1) a day on which participant experienced migraine headache pain intensity of mild, moderate, or severe as reported in eDiary or 2) an acute migraine-specific medication day. Total historical baseline is defined as the number of migraine days per month of any pain intensity in the 3 months prior to screening from the migraine history case report form (CRF). Moderate or severe historical baseline was defined as the number of migraine days per month of moderate or severe pain intensity in the 3 months prior to screening from the migraine history CRF.	Baseline (3 months prior to Screening); Month 1 (OLE Days 1 to 28), Month 2 (OLE Days 29 to 56) and Month 3 (OLE Days 57 to 84), and Overall OLE phase (84 days)
Percentage of Participants With at Least 50% Reduction From Historical Baseline in the Number of Migraine Days Per Month by Headache Pain Intensity at Months 1, 2 and 3 and Overall: OLE Phase	Percentages of participants with >= 50% reduction from historical baseline in the number of migraine days per month by headache pain intensity (total; moderate or severe) in each month and over the entire OLE Phase is reported in this outcome measure. A migraine day was defined as either 1) a day on which participant experienced migraine headache pain intensity of mild, moderate, or severe as reported in eDiary or 2) an acute migraine-specific medication day. Total historical baseline is defined as the number of migraine days per month of any pain intensity in the 3 months prior to screening from the migraine history CRF. Moderate or severe historical baseline was defined as the number of migraine days per month of moderate or severe pain intensity in the 3 months prior to screening from the migraine history CRF.	Baseline (3 months prior to Screening); Month 1 (OLE Days 1 to 28), Month 2 (OLE Days 29 to 56) and Month 3 (OLE Days 57 to 84), and Overall OLE phase (84 days)
Number of Participants With Adverse Events (AEs) by Intensity: DBT Phase	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participants or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with the treatment. AE intensity included mild, moderate and severe. Mild AE was defined as AEs which is usually transient and required only minimal treatment or therapeutic intervention. The event did not generally interfere with usual activities of daily living. Moderate AE was defined as AEs which was usually alleviated with additional specific therapeutic intervention. The event interfered with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the participants. Severe AE was defined as AE that interrupted with usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention.	DBT Phase: maximum of 45 days
Number of Participants With Serious AEs: DBT Phase	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participants or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with the treatment. A serious AE is any event that met any of the following criteria at any dose: death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a participant who received rimegepant or other important medical events.	DBT Phase: maximum of 45 days
Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participants or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with the treatment. Number of participants with AEs leading to study drug discontinuation have been reported in this outcome measure.	DBT Phase: maximum of 45 days
Number of Participants With Any On-Treatment Grade 3 to 4 Laboratory Abnormalities: DBT Phase	Laboratory tests included hematology and serum chemistry. All laboratory tests except glucose were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0, where Grade 3=severe events which require hospitalization or prolongation of hospitalization and Grade 4=life-threatening consequences requiring urgent intervention. Glucose was graded according to Division of Acquired Immune Deficiency Syndrome table for Grading Severity of Adult and Pediatric Adverse Events v2.1.	DBT Phase: maximum of 45 days
Number of Participants With AEs by Intensity: OLE Phase	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participants or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with the treatment. AE intensity included mild, moderate and severe. Mild AE was defined as AEs which is usually transient and required only minimal treatment or therapeutic intervention. The event did not generally interfere with usual activities of daily living. Moderate AE was defined as AEs which was usually alleviated with additional specific therapeutic intervention. The event interfered with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the participants. Severe AE was defined as AE that interrupted with usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention.	OLE Phase: maximum up to 12 weeks
Number of Participants With Serious AEs: OLE Phase	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participants or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with the treatment. A serious AE is any event that met any of the following criteria at any dose: death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a participant who received rimegepant or other important medical events.	OLE Phase: maximum up to 12 weeks
Number of Participants With AEs Leading to Study Drug Discontinuation: OLE Phase	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participants or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with the treatment. Number of participants with AEs leading to study drug discontinuation have been reported in this outcome measure.	OLE Phase: maximum up to 12 weeks
Number of Participants With On-Treatment Grade 3 to 4 Laboratory Abnormalities: OLE Phase	Laboratory tests included hematology and serum chemistry. All laboratory tests except glucose were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0, where Grade 3=severe events which require hospitalization or prolongation of hospitalization and Grade 4=life-threatening consequences requiring urgent intervention. Glucose was graded according to Division of Acquired Immune Deficiency Syndrome table for Grading Severity of Adult and Pediatric Adverse Events v2.1.	OLE Phase: maximum up to 12 weeks
Mean Change From Baseline in the Migraine Interictal Burden Scale (MIBS) Score at Weeks 4, 8, and 12: OLE Phase	MIBS was a 4-item self-administered questionnaire that measured interictal migraine related burden in the past 4 weeks on days when participants were not having an attack, using 4 domains: impairment in work or school; impairment in family and social life; difficulty making plans or commitments; emotional/affective and cognitive distress. The questionnaire specifically asked about the effect of the disease over the past 4 weeks on days without a headache attack. Response options included: don't know/not applicable (0), never (0), rarely (1), some of the time (2), much of the time (3), or most or all of the time (3). Each response associated with numerical score were summed across all 4 items resulting in a total MIBS score ranging from 0 to 12, and the level of interictal burden being categorized into the following: 0 for none and 12 for severe. Higher scores indicate worse interictal burden.	OLE phase: Baseline; Week 4, Week 8 and Week 12

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• Ashina M, McAllister P, Gaul C, Leyva-Rendon A, Ramirez LM, Nalpas C, Thiry A, Abraham L, Fountaine RJ, Fullerton T. Can rimegepant stop symptoms of a migraine attack in people who have not found triptans to work well or are not recommended to use triptans? A plain language summary of a clinical study. Pain Manag. 2026 Apr 3:1-15. doi: 10.1080/17581869.2026.2646705. Online ahead of print.
• Ashina M, McAllister P, Gaul C, Leyva-Rendon A, Ramirez LM, Nalpas C, Thiry A, Abraham L, Fountaine RJ, Fullerton T. Rimegepant for acute treatment of migraine in triptan-unsuitable adults: A randomized, double-blind, placebo-controlled phase 4 trial. Cephalalgia. 2025 Nov;45(11):3331024251395298. doi: 10.1177/03331024251395298. Epub 2025 Nov 18.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2022
• Primary Completion (Actual): March 10, 2025
• Study Completion (Actual): June 10, 2025

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (Actual): August 22, 2022

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Migraine; Headache; Acute Migraine; Acute treatment of Migraine in adults unsuitable for triptans
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Migraine Disorders; Headache; rimegepant sulfate
• Other Study ID Numbers: BHV3000-406; 2022-001175-14 (Registry Identifier: CTIS (EU)); C4951004 (Other Identifier: Alias Study Number); 2024-513269-37-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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