Efficacy and Safety Trial of Rimegepant for Migraine Prevention in Adults

Migraine Clinical Trial

Official title:

A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rimegepant in Migraine Prevention

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03732638
• Other study ID #: BHV3000-305
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: November 14, 2018
• Est. completion date: February 2, 2021

Study information

• Verified date: December 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1590
• Est. completion date: February 2, 2021
• Est. primary completion date: December 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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:

1. Age of onset of migraines prior to 50 years of age

2. Migraine attacks, on average, lasting 4 - 72 hours if untreated

3. Per subject report, 4 - 18 migraine attacks of moderate to severe intensity per month within the last 3 months prior to the Screening Visit

4. 6 or more migraine days during the Observation Period

5. Not more than 18 headache days during the Observation Period

6. Ability to distinguish migraine attacks from tension/cluster headaches

7. 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.

Exclusion Criteria:

2. Subject with a history of HIV disease

3. 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

4. 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).

5. 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.

6. 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

7. 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

8. Body mass index = 33 kg/m2

9. Subject has current diagnosis of major depressive disorder requiring treatment with atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder

10. History of gallstones or cholecystectomy.

11. 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.

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Rimegepant
Rimegepant 75 mg tablet EOD
• Placebo
Placebo tablet to match rimegepant tablet EOD

Locations

Country	Name	City	State
United States	Albuquerque Neuroscience, Inc.	Albuquerque	New Mexico
United States	Anaheim Clinical Trials	Anaheim	California
United States	Community Clinical Research Center	Anderson	Indiana
United States	Michigan Head Pain & Neurological Institute	Ann Arbor	Michigan
United States	Axiom Research, LLC	Apple Valley	California
United States	Tekton Research	Austin	Texas
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Hassman Research Institute	Berlin	New Jersey
United States	MedPharmics, LLC	Biloxi	Mississippi
United States	Northwest Clinical Trials, Inc	Boise	Idaho
United States	Boston Clinical Trials	Boston	Massachusetts
United States	Crescent City Headache and Neurology Center	Chalmette	Louisiana
United States	MDFirst Research-Chandler	Chandler	Arizona
United States	Charlottesville Medical Research	Charlottesville	Virginia
United States	Clinical Research Professionals, Inc.	Chesterfield	Missouri
United States	Cedar Crosse Research Center	Chicago	Illinois
United States	Hometown Urgent Care	Cincinnati	Ohio
United States	Axiom Research, LLC	Colton	California
United States	Meridian Clinical Research	Dakota Dunes	South Dakota
United States	FutureSearch Trials of Dallas, LP	Dallas	Texas
United States	Hometown Urgent Care and Research	Dayton	Ohio
United States	Neurology Diagnostics Research	Dayton	Ohio
United States	iResearch Atlanta, LLC	Decatur	Georgia
United States	OnSite Clinical Solutions	Dillon	South Carolina
United States	Aventiv Research, Inc	Dublin	Ohio
United States	Riverside Clinical Research	Edgewater	Florida
United States	Lillestol Research LLC	Fargo	North Dakota
United States	Ventavia Research Group, LLC	Fort Worth	Texas
United States	North Texas Institute of Neurology & Headache	Frisco	Texas
United States	Michigan Pain Consultants	Grand Rapids	Michigan
United States	PharmQuest, LLC	Greensboro	North Carolina
United States	Galiz Research	Hialeah	Florida
United States	Texas Center for Drug Development, Inc.	Houston	Texas
United States	Victorium Clinical Research	Houston	Texas
United States	R&R Clinical Research	Idaho Falls	Idaho
United States	The Center for Pharmaceutical Research, LLC	Kansas City	Missouri
United States	Clinical Investigation Specialists, Inc.	Kenosha	Wisconsin
United States	Volunteer Research Group	Knoxville	Tennessee
United States	eStudySite	La Mesa	California
United States	Multi-Specialty Research Associates, Inc.	Lake City	Florida
United States	Red Star Research, LLC	Lake Jackson	Texas
United States	FMC Science	Lampasas	Texas
United States	Nevada Headache Institute	Las Vegas	Nevada
United States	Synergy San Diego	Lemon Grove	California
United States	BTC of Lincoln, LLC	Lincoln	Rhode Island
United States	Baptist Health Center for Clinical Research	Little Rock	Arkansas
United States	Collaborative Neuroscience Network, LLC	Long Beach	California
United States	Central New York Clinical Research	Manlius	New York
United States	MedStar Georgetown Headache - Georgetown University	McLean	Virginia
United States	ActivMed Practices & Research, Inc.	Methuen	Massachusetts
United States	AppleMed Research Group, LLC	Miami	Florida
United States	Qps Mra, Llc	Miami	Florida
United States	Coastal Carolina Research Center	Mount Pleasant	South Carolina
United States	DelRicht Research	New Orleans	Louisiana
United States	New Orleans Center for Clinical Research	New Orleans	Louisiana
United States	Mid Hudson Medical Research, PLLC	New Windsor	New York
United States	Heartland Research Associates, LLC	Newton	Kansas
United States	Meridian Clinical Research, LLC	Norfolk	Nebraska
United States	Oklahoma Headache Center	Norman	Oklahoma
United States	Regeneris Medical	North Attleboro	Massachusetts
United States	Harmony Clinical Research	North Miami Beach	Florida
United States	Pacific Research Partners, LLC	Oakland	California
United States	Quality Clinical Research, Inc	Omaha	Nebraska
United States	Ormond Medical Arts Pharmaceutical Research Center	Ormond Beach	Florida
United States	Clinical Research of Philadelphia, LLC	Philadelphia	Pennsylvania
United States	MedPharmics, LLC	Phoenix	Arizona
United States	Island Neurological, A Division of Prohealth Care Associates, LLP	Plainview	New York
United States	Summit Research Network (Oregon) Inc.	Portland	Oregon
United States	Phoenix Medical Research	Prairie Village	Kansas
United States	PMG Research	Raleigh	North Carolina
United States	Sundance Clinical Research, LLC	Saint Louis	Missouri
United States	StudyMetrix Research	Saint Peters	Missouri
United States	Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)	Salem	Oregon
United States	Wasatch Clinical Research, LLC	Salt Lake City	Utah
United States	Victorium Clinical Research	San Antonio	Texas
United States	Artemis Institute for Clinical Research	San Diego	California
United States	Optimus Medical Group	San Francisco	California
United States	Artemis Institute for Clinical Research	San Marcos	California
United States	Neurological Research Institute	Santa Monica	California
United States	Seattle Women's	Seattle	Washington
United States	Carolina Research Institute Center, Inc.	Shelby	North Carolina
United States	California Neuroscience Research Medical Group	Sherman Oaks	California
United States	Clinvest Research LLC	Springfield	Missouri
United States	Ki Health Partners, LLC, dba New England Institute for Clinical Research	Stamford	Connecticut
United States	JSV Clinical Research Study Inc.	Tampa	Florida
United States	DM Clinical Research	Tomball	Texas
United States	Tucson Neuroscience Research	Tucson	Arizona
United States	Tidewater Integrated Medical Research	Virginia Beach	Virginia
United States	Family Medicine Specialists/CIS	Wauconda	Illinois
United States	Premiere Research Institute	West Palm Beach	Florida
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	Upstate Clinical Research Associates, LLC	Williamsville	New York
United States	Tekton Research	Yukon	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants Who Had = 50% Reduction in Moderate or Severe Migraine Days Per Month in the Last 4 Weeks 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 or severe monthly migraine days in the last 4 weeks of the DBT (Weeks 9 to 12) was less than or equal to half (50%) of the number of moderate or severe monthly migraine days in the OP.	OP and Weeks 9 to 12 of the DBT phase
Secondary	Change From Baseline in the Mean Number of Migraine Days Per Month Over the Entire Course 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.	OP and Weeks 1 to 12 of the DBT phase
Secondary	Frequency of Use of Rescue Medication Days Per Month in the Last Month 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.	Weeks 9 to 12 of the DBT phase
Secondary	Change From Baseline in the Mean Number of Total Migraine Days Per Month in the First Month 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.	OP and Weeks 1 to 4 of the DBT phase
Secondary	Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Study Drug Discontinuation in 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 rimegepant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention.	Weeks 1 to 12 of the DBT phase
Secondary	Number of Participants With AEs, SAEs, AEs Leading to Study Drug Discontinuation in the OLE 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 rimegepant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention.	OLE Phase (Weeks 13 through 64)
Secondary	Number of Participants With Clinically Significant Laboratory Abnormalities in 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 had a non-missing measurement in the DBT phase to be included for a given parameter.	Weeks 1 to 12 of the DBT phase
Secondary	Number of Participants With Clinically Significant Laboratory Abnormalities in the OLE Phase	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.	OLE Phase (Weeks 13 through 64)
Secondary	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	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.	Weeks 1 to 12 of the DBT phase
Secondary	Percentage of Participants With Elevations of AST or ALT > 3 x ULN Concurrent With TBL > 2 x ULN During the OLE 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 DBT phase to be included.	OLE Phase (Weeks 13 through 64)
Secondary	Number of Participants With Hepatic-related AEs and Hepatic-related AEs Leading to Discontinuation During 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.	Weeks 1 to 12 of the DBT phase
Secondary	Number of Participants With Hepatic-related AEs and Hepatic-related AEs Leading to Discontinuation During the OLE Phase	Hepatic AEs were defined as all preferred terms in the OLE phase under the "Hepatic Disorders" SMQ, except those preferred terms in the "Congenital, Familial, Neonatal and Genetic Disorders of the Liver" SMQ.	OLE Phase (Weeks 13 through 64)
Secondary	Mean Change From Baseline in the Migraine Specific Quality of Life (MSQoL) Role Function-Restrictive Domain Score at Week 12 of the DBT Phase	The Migraine Specific Quality of Life (MSQoL) is a self-administered, 14-item instrument that has been validated in 3 domains: role restriction, role prevention, and the emotional function. The role function-restrictive domain consists of 7 items that describe how migraine limits one's daily social and work-related activities. Participants respond to items using a 6-point scale: "none of the time," "a little bit of the time," "some of the time," "a good bit of the time," "most of the time," and "all of the time," which are assigned scores of 1 to 6, respectively. Item scores are recoded using (7 - original score). Next, raw dimension scores are computed as a sum of recoded item scores and rescaled from a 0 to 100 scale such that higher scores indicate better quality of life.; The change from baseline was calculated as the MSQoL restrictive role function domain score at Week 12 of the DBT phase minus the MSQoL restrictive role function domain score at baseline.	Baseline, Week 12 of the DBT Phase
Secondary	Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 of the DBT Phase	The Migraine Disability Assessment (MIDAS) is a retrospective, self-administered, 5-item questionnaire that measures headache-related disability as lost time due to headache from paid work or school, household work, and non-work activities. Participants provide the number of missed work or school days; missed household chores days; missed social or leisure activity days; and days at work or school, and separately at home, where productivity was reduced by half or more in the last 3 months (scale: 0 - 90 for each of 5 subscales). The 5 subscale scores are summed to compute the MIDAS total score (scale: 0 - 450). Lower scores indicate less headache-related disability.; The change from baseline was calculated as the MIDAS total score at Week 12 of the DBT phase minus the MIDAS total score at baseline.	Baseline, Week 12 of the DBT Phase