Efficacy and Safety Trial of Rimegepant for Migraine Prevention in Adults

• Sponsor: Biohaven Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03732638
• Collaborator: (none)
• Enrollment: 1,591
• Locations: 93
• Arms: 2
• Actual Duration (Months): 26.6
• Patients Per Site: 17.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Rimegepant; Drug: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1591 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rimegepant in Migraine Prevention
• Actual Study Start Date: Nov 14, 2018
• Actual Primary Completion Date: Dec 10, 2019
• Actual Study Completion Date: Feb 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rimegepant Rimegepant - Randomization Phase: Participants received a single oral dose of rimegepant 75 mg tablet every other day (EOD) for 12 weeks.	Drug: Rimegepant; Randomization Phase: Rimegepant (BHV-3000) 75 mg tablet EOD
Placebo Comparator: Placebo Placebo - Randomization Phase: Participants received a single oral dose of matching placebo tablet every other day (EOD) for 12 weeks.	Drug: Placebo; Randomization Phase: Placebo tablet to match rimegepant tablet EOD

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Mean Number of Total Migraine Days Per Month in the Last 4 Weeks of the DBT Phase [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-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.

Secondary Outcome Measures

1. 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]

   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.

2. 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]

   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.

3. 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]

   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.

4. 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]

   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.

5. 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]

   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.

6. Number of Participants With Clinically Significant Laboratory Abnormalities in the DBT Phase [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 had a non-missing measurement in the DBT phase to be included for a given parameter.

7. 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 [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 DBT phase to be included.

8. Number of Participants With Hepatic-related AEs and Hepatic-related AEs Leading to Discontinuation During the DBT Phase [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.

9. Mean Change From Baseline in the Migraine Specific Quality of Life (MSQoL) Role Function-Restrictive Domain Score at Week 12 of the DBT Phase [Baseline, 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.

10. Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 of the DBT Phase [Baseline, 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

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 screening).

4. 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.

5. 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

6. 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

7. Body mass index ≥ 33 kg/m2

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

9. History of gallstones or cholecystectomy.

10. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MDFirst Research-Chandler	Chandler	Arizona	United States	85286
2	MedPharmics, LLC	Phoenix	Arizona	United States	85015
3	Tucson Neuroscience Research	Tucson	Arizona	United States	85710
4	Baptist Health Center for Clinical Research	Little Rock	Arkansas	United States	72205
5	Anaheim Clinical Trials	Anaheim	California	United States	92801
6	Axiom Research, LLC	Apple Valley	California	United States	92307
7	Axiom Research, LLC	Colton	California	United States	92324
8	eStudySite	La Mesa	California	United States	91942
9	Synergy San Diego	Lemon Grove	California	United States	91945
10	Collaborative Neuroscience Network, LLC	Long Beach	California	United States	90806
11	Pacific Research Partners, LLC	Oakland	California	United States	94607
12	Artemis Institute for Clinical Research	San Diego	California	United States	92103
13	Optimus Medical Group	San Francisco	California	United States	94102
14	Artemis Institute for Clinical Research	San Marcos	California	United States	92078
15	Neurological Research Institute	Santa Monica	California	United States	90404
16	California Neuroscience Research Medical Group	Sherman Oaks	California	United States	91403
17	Ki Health Partners, LLC, dba New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
18	Riverside Clinical Research	Edgewater	Florida	United States	32132
19	Galiz Research	Hialeah	Florida	United States	33016
20	Multi-Specialty Research Associates, Inc.	Lake City	Florida	United States	32055
21	Qps Mra, Llc	Miami	Florida	United States	33143
22	AppleMed Research Group, LLC	Miami	Florida	United States	33155
23	Harmony Clinical Research	North Miami Beach	Florida	United States	33162
24	Ormond Medical Arts Pharmaceutical Research Center	Ormond Beach	Florida	United States	32174
25	JSV Clinical Research Study Inc.	Tampa	Florida	United States	33634
26	Premiere Research Institute	West Palm Beach	Florida	United States	33407
27	iResearch Atlanta, LLC	Decatur	Georgia	United States	30030
28	Northwest Clinical Trials, Inc	Boise	Idaho	United States	83704
29	R&R Clinical Research	Idaho Falls	Idaho	United States	83404
30	Cedar Crosse Research Center	Chicago	Illinois	United States	60607
31	Family Medicine Specialists/CIS	Wauconda	Illinois	United States	60084
32	Community Clinical Research Center	Anderson	Indiana	United States	46011
33	Heartland Research Associates, LLC	Newton	Kansas	United States	67114
34	Phoenix Medical Research	Prairie Village	Kansas	United States	66208
35	Heartland Research Associates, LLC	Wichita	Kansas	United States	67207
36	Crescent City Headache and Neurology Center	Chalmette	Louisiana	United States	70043
37	New Orleans Center for Clinical Research	New Orleans	Louisiana	United States	70119
38	DelRicht Research	New Orleans	Louisiana	United States	70124
39	Boston Clinical Trials	Boston	Massachusetts	United States	02131
40	ActivMed Practices & Research, Inc.	Methuen	Massachusetts	United States	01844
41	Regeneris Medical	North Attleboro	Massachusetts	United States	02760
42	Michigan Head Pain & Neurological Institute	Ann Arbor	Michigan	United States	48104
43	Michigan Pain Consultants	Grand Rapids	Michigan	United States	49503
44	MedPharmics, LLC	Biloxi	Mississippi	United States	39531
45	Clinical Research Professionals, Inc.	Chesterfield	Missouri	United States	63005
46	The Center for Pharmaceutical Research, LLC	Kansas City	Missouri	United States	64114
47	Sundance Clinical Research, LLC	Saint Louis	Missouri	United States	63141
48	StudyMetrix Research	Saint Peters	Missouri	United States	63303
49	Clinvest Research LLC	Springfield	Missouri	United States	65810
50	Meridian Clinical Research, LLC	Norfolk	Nebraska	United States	68701
51	Quality Clinical Research, Inc	Omaha	Nebraska	United States	68114
52	Nevada Headache Institute	Las Vegas	Nevada	United States	89113
53	Hassman Research Institute	Berlin	New Jersey	United States	08009
54	Albuquerque Neuroscience, Inc.	Albuquerque	New Mexico	United States	87109
55	Central New York Clinical Research	Manlius	New York	United States	13104
56	Mid Hudson Medical Research, PLLC	New Windsor	New York	United States	12553
57	Island Neurological, A Division of Prohealth Care Associates, LLP	Plainview	New York	United States	11803
58	Upstate Clinical Research Associates, LLC	Williamsville	New York	United States	14221
59	PharmQuest, LLC	Greensboro	North Carolina	United States	27408
60	PMG Research	Raleigh	North Carolina	United States	27609
61	Carolina Research Institute Center, Inc.	Shelby	North Carolina	United States	28150
62	Lillestol Research LLC	Fargo	North Dakota	United States	58104
63	Hometown Urgent Care	Cincinnati	Ohio	United States	45215
64	Hometown Urgent Care and Research	Dayton	Ohio	United States	45424
65	Neurology Diagnostics Research	Dayton	Ohio	United States	45459
66	Aventiv Research, Inc	Dublin	Ohio	United States	43016
67	Oklahoma Headache Center	Norman	Oklahoma	United States	73072
68	Tekton Research	Yukon	Oklahoma	United States	73099
69	Summit Research Network (Oregon) Inc.	Portland	Oregon	United States	97210
70	Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)	Salem	Oregon	United States	97301
71	Clinical Research of Philadelphia, LLC	Philadelphia	Pennsylvania	United States	19114
72	BTC of Lincoln, LLC	Lincoln	Rhode Island	United States	02865
73	OnSite Clinical Solutions	Dillon	South Carolina	United States	29536
74	Coastal Carolina Research Center	Mount Pleasant	South Carolina	United States	29464
75	Meridian Clinical Research	Dakota Dunes	South Dakota	United States	57049
76	Volunteer Research Group	Knoxville	Tennessee	United States	37920
77	Tekton Research	Austin	Texas	United States	78745
78	FutureSearch Trials of Dallas, LP	Dallas	Texas	United States	75231
79	Ventavia Research Group, LLC	Fort Worth	Texas	United States	76104
80	North Texas Institute of Neurology & Headache	Frisco	Texas	United States	75034
81	Victorium Clinical Research	Houston	Texas	United States	77024
82	Texas Center for Drug Development, Inc.	Houston	Texas	United States	77081
83	Red Star Research, LLC	Lake Jackson	Texas	United States	77566
84	FMC Science	Lampasas	Texas	United States	76550
85	Victorium Clinical Research	San Antonio	Texas	United States	78230
86	DM Clinical Research	Tomball	Texas	United States	77375
87	Wasatch Clinical Research, LLC	Salt Lake City	Utah	United States	84107
88	Charlottesville Medical Research	Charlottesville	Virginia	United States	22911
89	MedStar Georgetown Headache - Georgetown University	McLean	Virginia	United States	22102
90	Tidewater Integrated Medical Research	Virginia Beach	Virginia	United States	23454
91	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
92	Seattle Women's	Seattle	Washington	United States	98105
93	Clinical Investigation Specialists, Inc.	Kenosha	Wisconsin	United States	53144

Sponsors and Collaborators

• Biohaven Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Aug 25, 2020
• Statistical Analysis Plan - Feb 9, 2021

More Information

Publications

None provided.

• Responsible Party: Biohaven Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03732638
• Other Study ID Numbers: BHV3000-305
• First Posted: Nov 6, 2018
• Last Update Posted: Aug 9, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Biohaven Pharmaceuticals, Inc.: Migraine; Prevention; Prophylaxis
• Additional relevant MeSH terms: Migraine Disorders

Study Results

Participant Flow

Recruitment Details	The study was conducted at 92 sites in the United States.
Pre-assignment Detail	A total of 1591 participants were enrolled in the study, of which 747 subjects were randomized and 844 were not randomized. The study was divided into 4 phases: a 4-week observation period (OP), a 12-week double-blind treatment (DBT) phase, a 52-week open-label extension (OLE) phase, and an 8-week follow-up safety phase.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Period Title: Overall Study
STARTED	370	371
COMPLETED	316	310
NOT COMPLETED	54	61

Baseline Characteristics

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase	Total
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.	Total of all reporting groups
Overall Participants	370	371	741
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.3 (13.01)	41.1 (13.13)	41.2 (13.06)
Sex: Female, Male (Count of Participants)
Female	300 81.1%	313 84.4%	613 82.7%
Male	70 18.9%	58 15.6%	128 17.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	105 28.4%	98 26.4%	203 27.4%
Not Hispanic or Latino	265 71.6%	273 73.6%	538 72.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	6 1.6%	1 0.3%	7 0.9%
Asian	1 0.3%	7 1.9%	8 1.1%
Native Hawaiian or Other Pacific Islander	0 0%	3 0.8%	3 0.4%
Black or African American	62 16.8%	49 13.2%	111 15%
White	295 79.7%	309 83.3%	604 81.5%
More than one race	6 1.6%	2 0.5%	8 1.1%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Mean Number of Total Migraine Days Per Month in the Last 4 Weeks of the DBT Phase
Description	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.
Time Frame	OP and Weeks 9 to 12 of the DBT phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on evaluable modified intent to treat (mITT) participants. Evaluable participants are those with ≥ 14 days of electronic diary efficacy data (not necessarily consecutive) in both the OP and ≥ 1 month (4-week interval) in the DBT phase.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	348	347
Least Squares Mean (95% Confidence Interval) [Total Migraine Days per Month]	-4.3	-3.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant - Randomization Phase, Placebo - Randomization Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0099
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.46 to - 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants Who Had ≥ 50% Reduction in Moderate or Severe Migraine Days Per Month in the Last 4 Weeks of the DBT Phase
Description	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.
Time Frame	OP and Weeks 9 to 12 of the DBT phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on evaluable mITT participants.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	348	347
Number (95% Confidence Interval) [percentage of participants]	49.1 13.3%	41.5 11.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant - Randomization Phase, Placebo - Randomization Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0438
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	7.6
	Confidence Interval	(2-Sided) 95%; 0.2 to 14.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in the Mean Number of Migraine Days Per Month Over the Entire Course of the DBT Phase
Description	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.
Time Frame	OP and Weeks 1 to 12 of the DBT phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on evaluable mITT participants.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	348	347
Least Squares Mean (95% Confidence Interval) [Total Migraine Days per Month]	-3.6	-2.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant - Randomization Phase, Placebo - Randomization Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0017
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	- 0.8
	Confidence Interval	(2-Sided) 95%; - 1.34 to -0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Frequency of Use of Rescue Medication Days Per Month in the Last Month of the DBT Phase
Description	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.
Time Frame	Weeks 9 to 12 of the DBT phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on evaluable mITT participants

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo table EOD for 12 weeks.
Measure Participants	348	347
Least Squares Mean (95% Confidence Interval) [rescue medication Days per Month]	3.7	4.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant - Randomization Phase, Placebo - Randomization Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3868
	Comments	P-value ≥ 0.05; therefore, all secondary endpoints listed after this endpoint in the hierarchy were not tested.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; - 0.80 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in the Mean Number of Total Migraine Days Per Month in the First Month of the DBT Phase
Description	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.
Time Frame	OP and Weeks 1 to 4 of the DBT phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on evaluable mITT participants.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	348	347
Least Squares Mean (95% Confidence Interval) [migraine days per month]	-2.9	-1.7

6. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Study Drug Discontinuation in the DBT Phase
Description	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.
Time Frame	Weeks 1 to 12 of the DBT phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on the participants treated in the DBT phase.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	370	371
AEs	133 35.9%	133 35.8%
SAEs	3 0.8%	4 1.1%
AEs leading to study drug discontinuation	7 1.9%	4 1.1%

7. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities in the DBT Phase
Description	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.
Time Frame	Weeks 1 to 12 of the DBT phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on the participants treated in the DBT phase.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	370	371
Eosinophils	0 0%	0 0%
Hemoglobin	0 0%	1 0.3%
Lymphocytes, high	0 0%	0 0%
Lymphocytes, low	0 0%	0 0%
Neutrophils	4 1.1%	2 0.5%
Platelets	1 0.3%	0 0%
White Blood Cells	1 0.3%	0 0%
Alanine Aminotransferase (ALT)	1 0.3%	0 0%
Aspartate Aminotransferase (AST)	1 0.3%	0 0%
Albumin	0 0%	0 0%
Alkaline Phosphatase	0 0%	0 0%
Bicarbonate	0 0%	0 0%
Bilirubin	0 0%	0 0%
Calcium, high	0 0%	0 0%
Calcium, low	0 0%	0 0%
Cholesterol	0 0%	0 0%
Creatine Kinase	4 1.1%	4 1.1%
Creatinine	0 0%	0 0%
Glucose, high	0 0%	0 0%
Glucose, low	0 0%	0 0%
LDL-cholesterol	2 0.5%	0 0%
LDL-cholesterol, fasting	0 0%	0 0%
LDL-cholesterol, not fasting	2 0.5%	0 0%
Lactate Dehydrogenase	0 0%	0 0%
Potassium, high	1 0.3%	2 0.5%
Potassium, low	0 0%	0 0%
Sodium, high	0 0%	0 0%
Sodium, low	0 0%	0 0%
Triglycerides	0 0%	0 0%
Triglycerides, fasting	0 0%	0 0%
Triglycerides, not fasting	0 0%	0 0%
Uric acid	0 0%	0 0%
Glomerular Filtration Rate, Estimated	1 0.3%	0 0%
Urine Glucose	0 0%	0 0%
Urine Protein	1 0.3%	0 0%

8. Secondary Outcome

Title	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
Description	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.
Time Frame	Weeks 1 to 12 of the DBT phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on the participants treated in the DBT phase.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	370	371
Number (95% Confidence Interval) [Percentage of participants]	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants With Hepatic-related AEs and Hepatic-related AEs Leading to Discontinuation During the DBT Phase
Description	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.
Time Frame	Weeks 1 to 12 of the DBT phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on the participants treated in the DBT phase.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	370	371
Hepatic-related AE	6 1.6%	2 0.5%
Severe hepatic-related AE	0 0%	0 0%
Hepatic-related SAE	0 0%	0 0%
Hepatic-related AE leading to study drug discontinuation	2 0.5%	2 0.5%

10. Secondary Outcome

Title	Mean Change From Baseline in the Migraine Specific Quality of Life (MSQoL) Role Function-Restrictive Domain Score at Week 12 of the DBT Phase
Description	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.
Time Frame	Baseline, Week 12 of the DBT Phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on evaluable mITT participants.

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	269	266
Least Squares Mean (95% Confidence Interval) [score on a scale]	18.0	14.6

11. Secondary Outcome

Title	Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 of the DBT Phase
Description	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.
Time Frame	Baseline, Week 12 of the DBT Phase

Outcome Measure Data

Analysis Population Description

The analysis was performed on evaluable mITT participants

Arm/Group Title	Rimegepant - Randomization Phase	Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.	Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
Measure Participants	269	266
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	-11.8	-11.7

Adverse Events

Time Frame	Adverse events were reported from the first dose of study treatment through the end of study treatment in the DBT phase (up to approximately 12 weeks).
Adverse Event Reporting Description	The analysis was performed on treated participants.
Arm/Group Title	Rimegepant - Randomization Phase		Placebo - Randomization Phase
Arm/Group Description	Participants received a single oral dose of rimegepant 75 mg tablet EOD for 12 weeks.		Participants received a single oral dose of matching placebo tablet EOD for 12 weeks.
All Cause Mortality
	Rimegepant - Randomization Phase		Placebo - Randomization Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/370 (0%)		0/371 (0%)
Serious Adverse Events
	Rimegepant - Randomization Phase		Placebo - Randomization Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/370 (0.8%)		4/371 (1.1%)
Infections and infestations
Gastroenteritis	1/370 (0.3%)		0/371 (0%)
Appendicitis	0/370 (0%)		1/371 (0.3%)
Pneumonia	0/370 (0%)		1/371 (0.3%)
Pyelonephritis	0/370 (0%)		1/371 (0.3%)
Injury, poisoning and procedural complications
Overdose	0/370 (0%)		1/371 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma	1/370 (0.3%)		0/371 (0%)
Psychiatric disorders
Suicide attempt	1/370 (0.3%)		0/371 (0%)
Other (Not Including Serious) Adverse Events
	Rimegepant - Randomization Phase		Placebo - Randomization Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/370 (0%)		0/371 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding study results for a period that is less than or equal to 60 days from the date that the communication is submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot unilaterally extend the embargo.