Last reviewed · How we verify

NCT03732638

Efficacy and Safety Trial of Rimegepant for Migraine Prevention in Adults

Completed Phase 2, PHASE3 Results posted Last updated 7 June 2024
What this trial tests

Phase 2, PHASE3 trial testing Rimegepant in Migraine in 1,590 participants. Completed in 2 February 2021.

Timeline
14 November 2018
Primary endpoint
10 December 2019
2 February 2021

Quick facts

Lead sponsorPfizer
PhasePhase 2, PHASE3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposeprevention
Enrollment1,590
Start date14 November 2018
Primary completion10 December 2019
Estimated completion2 February 2021
Sites93 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Migraine. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in the Mean Number of Total Migraine Days Per Month in the Last 4 Weeks of the DBT Phase Primary · OP and Weeks 9 to 12 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-specifi

GroupValue95% CI
Rimegepant - Randomization Phase-4.3-4.83 – -3.87
Placebo - Randomization Phase-3.5-4 – -3.04
Number of Participants Who Had ≥ 50% Reduction in Moderate or Severe Migraine Days Per Month in the Last 4 Weeks of the DBT Phase Secondary · OP and Weeks 9 to 12 of the DBT phase

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (as previously described). 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. A moderate or severe migraine day was a migraine day of moderate or severe pain intensity. Months were defined as 28-day intervals. A reduction of at least 50% in the mean number of moderate or severe monthly migraine days was determined if the number of moderate

GroupValue95% CI
Rimegepant - Randomization Phase49.143.9 – 54.3
Placebo - Randomization Phase41.536.3 – 46.7
Change From Baseline in the Mean Number of Migraine Days Per Month Over the Entire Course of the DBT Phase Secondary · OP and Weeks 1 to 12 of the DBT phase

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (as previously described). 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 DBT phase (Weeks 1 to 12) minus the number of monthly migraine days during the OP.

GroupValue95% CI
Rimegepant - Randomization Phase-3.6-3.97 – -3.17
Placebo - Randomization Phase-2.7-3.14 – -2.34
Frequency of Use of Rescue Medication Days Per Month in the Last Month of the DBT Phase Secondary · Weeks 9 to 12 of the DBT phase

A rescue medication day was a day on which the participant took triptan, ergotamine, or other permitted medication to acutely treat headache or aura. Months were defined as 28-day intervals.

GroupValue95% CI
Rimegepant - Randomization Phase3.73.29 – 4.15
Placebo - Randomization Phase4.03.53 – 4.39
Change From Baseline in the Mean Number of Total Migraine Days Per Month in the First Month of the DBT Phase Secondary · OP and Weeks 1 to 4 of the DBT phase

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (as previously described). 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 first 4 weeks of the DBT phase (Weeks 1 to 4) minus the number of monthly migraine days during the OP.

GroupValue95% CI
Rimegepant - Randomization Phase-2.9-3.32 – -2.46
Placebo - Randomization Phase-1.7-2.15 – -1.29
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Study Drug Discontinuation in the DBT Phase Secondary · Weeks 1 to 12 of the DBT phase

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition on-treatment in a patient or clinical investigation participant administered an investigational (medicinal) product and that did not necessarily have a causal relationship with this treatment. An SAE was defined as any event that met any of the following criteria: 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 rimeg

AEs
GroupValue95% CI
Rimegepant - Randomization Phase133
Placebo - Randomization Phase133
SAEs
GroupValue95% CI
Rimegepant - Randomization Phase3
Placebo - Randomization Phase4
AEs leading to study drug discontinuation
GroupValue95% CI
Rimegepant - Randomization Phase7
Placebo - Randomization Phase4
Number of Participants With AEs, SAEs, AEs Leading to Study Drug Discontinuation in the OLE Phase Secondary · OLE Phase (Weeks 13 through 64)

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition on-treatment in a patient or clinical investigation participant administered an investigational (medicinal) product and that did not necessarily have a causal relationship with this treatment. An SAE was defined as any event that met any of the following criteria: 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 rimeg

AEs
GroupValue95% CI
DBT Rimegepant/OL Rimegepant150
DBT Placebo/OL Rimegepant162
SAEs
GroupValue95% CI
DBT Rimegepant/OL Rimegepant7
DBT Placebo/OL Rimegepant6
AEs leading to study drug discontinuation
GroupValue95% CI
DBT Rimegepant/OL Rimegepant9
DBT Placebo/OL Rimegepant8
Number of Participants With Clinically Significant Laboratory Abnormalities in the DBT Phase Secondary · Weeks 1 to 12 of the DBT phase

Clinically significant laboratory abnormalities were defined as Grade 3 to 4 laboratory test results according to numeric laboratory test criteria found in Common Technical Criteria for Adverse Events (CTCAE) Version 5.0 (2017) if available; otherwise, according to Division of Acquired Immune Deficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017) for glucose, LDL-cholesterol, uric acid, and urinalysis. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis. Participants must have ha

Eosinophils
GroupValue95% CI
Rimegepant - Randomization Phase0
Placebo - Randomization Phase0
Hemoglobin
GroupValue95% CI
Rimegepant - Randomization Phase0
Placebo - Randomization Phase1
Lymphocytes, high
GroupValue95% CI
Rimegepant - Randomization Phase0
Placebo - Randomization Phase0
Lymphocytes, low
GroupValue95% CI
Rimegepant - Randomization Phase0
Placebo - Randomization Phase0
Neutrophils
GroupValue95% CI
Rimegepant - Randomization Phase4
Placebo - Randomization Phase2
Platelets
GroupValue95% CI
Rimegepant - Randomization Phase1
Placebo - Randomization Phase0
White Blood Cells
GroupValue95% CI
Rimegepant - Randomization Phase1
Placebo - Randomization Phase0
Alanine Aminotransferase (ALT)
GroupValue95% CI
Rimegepant - Randomization Phase1
Placebo - Randomization Phase0
Number of Participants With Clinically Significant Laboratory Abnormalities in the OLE Phase Secondary · OLE Phase (Weeks 13 through 64)

Clinically significant laboratory abnormalities were defined as Grade 3 to 4 laboratory test results according to numeric laboratory test criteria found in CTCAE Version 5.0 (2017) if available; otherwise, according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017) for glucose, LDL-cholesterol, uric acid, and urinalysis. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis. Participants must have had a non-missing measurement in the OLE phase to be included for a given parameter.

Eosinophils
GroupValue95% CI
DBT Rimegepant/OL Rimegepant0
DBT Placebo/OL Rimegepant0
Hemoglobin
GroupValue95% CI
DBT Rimegepant/OL Rimegepant1
DBT Placebo/OL Rimegepant1
Lymphocytes, high
GroupValue95% CI
DBT Rimegepant/OL Rimegepant0
DBT Placebo/OL Rimegepant0
Lymphocytes, low
GroupValue95% CI
DBT Rimegepant/OL Rimegepant1
DBT Placebo/OL Rimegepant0
Neutrophils
GroupValue95% CI
DBT Rimegepant/OL Rimegepant1
DBT Placebo/OL Rimegepant1
Platelets
GroupValue95% CI
DBT Rimegepant/OL Rimegepant0
DBT Placebo/OL Rimegepant0
White Blood Cells
GroupValue95% CI
DBT Rimegepant/OL Rimegepant0
DBT Placebo/OL Rimegepant0
Alanine Aminotransferase (ALT)
GroupValue95% CI
DBT Rimegepant/OL Rimegepant0
DBT Placebo/OL Rimegepant5
Number of Participants With Elevations of AST or ALT > 3 x Upper Limit of Normal (ULN) Concurrent With Total Bilirubin (TBL) > 2 x ULN During the DBT Phase Secondary · Weeks 1 to 12 of the DBT phase

Elevations of AST or ALT \> 3 x ULN concurrent with TBL \> 2 x ULN were defined as elevations on the same collection date. Participants must have had a non-missing AST, ALT, or TBL measurement in the OLE phase to be included.

GroupValue95% CI
Rimegepant - Randomization Phase00.00 – 1.24
Placebo - Randomization Phase00.00 – 1.24
Percentage of Participants With Elevations of AST or ALT > 3 x ULN Concurrent With TBL > 2 x ULN During the OLE Phase Secondary · OLE Phase (Weeks 13 through 64)

Elevations of AST or ALT \> 3 x ULN concurrent with TBL \> 2 x ULN were defined as elevations on the same collection date. Participants must have had a non-missing AST, ALT, or TBL measurement in the DBT phase to be included.

GroupValue95% CI
DBT Rimegepant/OL Rimegepant00.00 – 1.51
DBT Placebo/OL Rimegepant00.00 – 1.52
Number of Participants With Hepatic-related AEs and Hepatic-related AEs Leading to Discontinuation During the DBT Phase Secondary · Weeks 1 to 12 of the DBT phase

Hepatic AEs were defined as all preferred terms in the DBT phase under the "Hepatic Disorders" Standardized Medical Dictionary (Version 21.1) for Regulatory Activities Query (SMQ), except those preferred terms in the "Congenital, Familial, Neonatal and Genetic Disorders of the Liver" SMQ.

Hepatic-related AE
GroupValue95% CI
Rimegepant - Randomization Phase6
Placebo - Randomization Phase2
Severe hepatic-related AE
GroupValue95% CI
Rimegepant - Randomization Phase0
Placebo - Randomization Phase0
Hepatic-related SAE
GroupValue95% CI
Rimegepant - Randomization Phase0
Placebo - Randomization Phase0
Hepatic-related AE leading to study drug discontinuation
GroupValue95% CI
Rimegepant - Randomization Phase2
Placebo - Randomization Phase2

Adverse events — posted to ClinicalTrials.gov

Time frame: DBT Phase: From the first dose in the DBT Phase (Week 1) to Week 12 OLE Phase: Week 13 to Week 64 Follow-up phase: 8 weeks after the end of treatment (maximum duration of treatment: 64 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rimegepant - Randomization Phase
Serious: 3/370 (1%)
Deaths: 0/370
Placebo - Randomization Phase
Serious: 4/371 (1%)
Deaths: 0/371
DBT Rimegepant/OLE Rimegepant - OLE Phase
Serious: 7/302 (2%)
Deaths: 1/302
DBT Placebo/OLE Rimegepant - OLE Phase
Serious: 6/301 (2%)
Deaths: 1/301
DBT Rimegepant/OLE Rimegepant - Follow-up Phase
Serious: 2/332 (1%)
Deaths: 0/332
DBT Placebo/OLE Rimegepant - Follow-up Phase
Serious: 2/336 (1%)
Deaths: 0/336

Serious adverse events (27 terms)

ReactionSystemRimegepant - Randomization…Placebo - Randomization Ph…DBT Rimegepant/OLE Rimegep…DBT Placebo/OLE Rimegepant…DBT Rimegepant/OLE Rimegep…DBT Placebo/OLE Rimegepant…
GastroenteritisInfections and infestations——————
AppendicitisInfections and infestations——————
PneumoniaInfections and infestations——————
PyelonephritisInfections and infestations——————
Malignant melanomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)——————
Suicide attemptPsychiatric disorders——————
OverdoseInjury, poisoning and procedural complications——————
Abdominal pain lowerGastrointestinal disorders——————
ColitisGastrointestinal disorders——————
Gastric ulcerGastrointestinal disorders——————
Gastrooesophageal reflux diseaseGastrointestinal disorders——————
DiverticulitisInfections and infestations——————
Septic shockInfections and infestations——————
Urinary tract infectionInfections and infestations——————
Atrial fibrillationCardiac disorders——————
Myocardial infarctionCardiac disorders——————
AnaemiaBlood and lymphatic system disorders——————
CholelithiasisHepatobiliary disorders——————
Back painMusculoskeletal and connective tissue disorders——————
Adenocarcinoma of colonNeoplasms benign, malignant and unspecified (incl cysts and polyps)——————
MigraineNervous system disorders——————
Depressive delusionPsychiatric disorders——————
Suicidal ideationPsychiatric disorders——————
Aortic dissectionVascular disorders——————
CholecystitisHepatobiliary disorders——————
Other adverse events (2 terms — click to expand)

ReactionSystemRimegepant - Randomization…Placebo - Randomization Ph…DBT Rimegepant/OLE Rimegep…DBT Placebo/OLE Rimegepant…DBT Rimegepant/OLE Rimegep…DBT Placebo/OLE Rimegepant…
NasopharyngitisInfections and infestations——————
Upper respiratory tract infectionInfections and infestations——————

Most-reported serious reactions: Gastroenteritis, Appendicitis, Pneumonia, Pyelonephritis, Malignant melanoma, Suicide attempt, Overdose, Abdominal pain lower.

Data from ClinicalTrials.gov NCT03732638 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial.
    Croop R, Lipton RB, Kudrow D, Stock DA, et al · · 2021 · cited 229× · PMID 33338437 · DOI 10.1016/s0140-6736(20)32544-7
  2. Therapeutic novelties in migraine: new drugs, new hope?
    Do TP, Guo S, Ashina M. · · 2019 · cited 79× · PMID 30995909 · DOI 10.1186/s10194-019-0974-3
  3. New Generation Gepants: Migraine Acute and Preventive Medications.
    Moreno-Ajona D, Villar-Martínez MD, Goadsby PJ. · · 2022 · cited 55× · PMID 35329982 · DOI 10.3390/jcm11061656
  4. Gepants for Acute and Preventive Migraine Treatment: A Narrative Review.
    Rissardo JP, Caprara ALF. · · 2022 · cited 43× · PMID 36552072 · DOI 10.3390/brainsci12121612
  5. Gepants - a long way to cure: a narrative review.
    Altamura C, Brunelli N, Marcosano M, Fofi L, et al · · 2022 · cited 32× · PMID 35650458 · DOI 10.1007/s10072-022-06184-8
  6. Atogepant Is Not Associated With Clinically Meaningful Alanine Aminotransferase Elevations in Healthy Adults.
    Min KC, Kraft WK, Bondiskey P, Colón-González F, et al · · 2021 · cited 18× · PMID 33142014 · DOI 10.1111/cts.12917
  7. Mapping Migraine-Specific Quality of Life to Health State Utilities in Patients Receiving Rimegepant.
    Johnston KM, L'Italien G, Popoff E, Powell L, et al · · 2021 · cited 12× · PMID 34455556 · DOI 10.1007/s12325-021-01897-2
  8. Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications.
    Özge A, Baykan B, Bıçakçı Ş, Ertaş M, et al · · 2024 · cited 11× · PMID 38938785 · DOI 10.3389/fneur.2024.1402569

Verify or expand the search:

Other trials of Rimegepant

Trials testing the same drug.

Other recruiting trials for Migraine

Currently open trials in the same condition.

Other Pfizer trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03732638.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing