Safety and Efficacy in Adult Subjects With Acute Migraines

• Sponsor: Biohaven Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03237845
• Collaborator: (none)
• Enrollment: 1,499
• Locations: 50
• Arms: 2
• Actual Duration (Months): 6.2
• Patients Per Site: 30
• Patients Per Site Per Month: 4.9

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of BHV-3000 (rimegepant) versus placebo in subjects with Acute Migraines

Condition or Disease	Intervention/Treatment	Phase
Migraine, With or Without Aura	Drug: Rimegepant; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1499 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized Controlled TrialRandomized Controlled Trial
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-blind to Sponsor, Investigator and Participant
• Primary Purpose: Treatment
• Official Title: BHV3000-302 : Phase 3: Double-Blind, Randomized, Placebo-Controlled, Safety and Efficacy Trial of BHV-3000 (Rimegepant) for the Acute Treatment of Migraine
• Actual Study Start Date: Jul 27, 2017
• Actual Primary Completion Date: Jan 25, 2018
• Actual Study Completion Date: Jan 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rimegepant 75 mg Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Drug: Rimegepant; 75 mg tablet QD; Other Names: BHV-3000
Placebo Comparator: Placebo Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Drug: Placebo; Placebo tablet to match rimegepant dose QD

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Freedom From Pain at 2 Hours Post-dose [2 Hours post-dose]

   Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic diary (eDiary). Pain freedom was defined as pain level of none.

2. Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose [2 Hours]

   MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at onset that was absent post-dose.

Secondary Outcome Measures

1. Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose [2 hours post-dose]

   Photophobia (sensitivity to light) status was measured as absent or present in the eDiary. Freedom from photophobia was defined as photophobia absent.

2. Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose [2 hours post-dose]

   Phonophobia (sensitivity to sound) status was measured as absent or present in the eDiary. Freedom from phonophobia was defined as phonophobia absent.

3. Percentage of Participants With Pain Relief at 2 Hours Post-dose [2 hours post-dose]

   Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild.

4. Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose [2 hours post-dose]

   Nausea status was measured as absent or present in the eDiary. Freedom from nausea was defined as nausea absent.

5. Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose [24 hours post-dose]

   Participants who did not experience relief of their migraine headache at the end of 2 hours after dosing with study medication (and after the 2-hour assessments had been completed on the eDiary) were permitted to use the following rescue medications: aspirin, ibuprofen, acetaminophen up to 1000 mg/day (this includes Excedrin Migraine), naproxen (or any other type of nonsteroidal anti-inflammatory drug), antiemetics (e.g., metoclopramide or promethazine), or baclofen. The participant's use of rescue medication was recorded by the participant in a paper diary.

6. Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose [From 2 hours up to 24 hours post-dose]

   Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.

7. Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose [From 2 hours up to 24 hours post-dose]

   Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.

8. Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose [From 2 hours up to 48 hours post-dose]

   Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.

9. Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose [From 2 hours up to 48 hours post-dose]

   Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.

10. Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose [From 2 hours up to 48 hours post-dose]

    Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relapse was defined as pain level of mild, moderate, or severe after 2 hours up to 48 hours for the participants who were pain-free at 2 hours post-dose.

11. Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose [2 hours post-dose]

    Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

1. Patient has at least 1 year history of migraines (with or without aura), consistent with a diagnosis according to the International Classification of Headache Disorder, 3rd Edition, Beta version[1] including the following:

• Not more than 8 attacks of moderate or severe intensity per month within last 3 months

• Consistent migraine headaches of at least 2 migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening Period

1. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening Period

2. Patients on prophylactic migraine medication are permitted to remain on therapy provided they have been on a stable dose for at least 3 months prior to study entry.

3. Patients with contraindications for use of triptans may be included provided they meet all other study entry criteria.

Key Exclusion Criteria:

1. Patient history of HIV disease

2. Patient history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Patients 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 patients can be included who have stable hypertension and/or diabetes for 3 months prior to being enrolled)

4. Patient has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (eg, schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments

5. Patient has a history of gastric, or small intestinal surgery, or has a disease that causes malabsorption.

6. The patient has a history or current evidence of any significant and/or unstable medical conditions (eg, history of congenital heart disease or arrhythmia, known suspected infection, hepatitisB 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 ofthe trial

7. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or patients who have met DSM-V criteria for any significant substance use disorder within thepast 12 months from the date of the screening visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Coastal Clinical Research	Mobile	Alabama	United States	36608
2	Thunderbird Internal Medicine / Radiant Research, Inc.	Glendale	Arizona	United States	85306
3	Woodland Research Northwest, LLC	Rogers	Arkansas	United States	72758
4	eStudySite	La Mesa	California	United States	91942
5	Collaborative Neuroscience Network, LLC	Long Beach	California	United States	90806
6	Pharmacology Research Institute	Los Alamitos	California	United States	90720
7	Pharmacology Research Institute	Newport Beach	California	United States	92660
8	Pacific Research Partners LLC	Oakland	California	United States	94607
9	National Research Institute	Panorama City	California	United States	91402
10	California Neuroscience Research Medical Group, Inc.	Sherman Oaks	California	United States	91403
11	Clinical Trials of the Rockies	Denver	Colorado	United States	80209
12	AGA Clinical Trials	Hialeah	Florida	United States	33012
13	Clinical Neuroscience Solutions	Jacksonville	Florida	United States	32256
14	Renstar Medical Research	Ocala	Florida	United States	34471
15	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32801
16	Meridien Research	Tampa	Florida	United States	33634
17	Radiant Research, Inc.	Atlanta	Georgia	United States	30328
18	Savannah Neurology Specialists	Savannah	Georgia	United States	31406
19	Christie Clinic, LLC	Champaign	Illinois	United States	61820
20	PMG Research of McFrland Clinic	Ames	Iowa	United States	50010
21	Heartland Research Associates, LLC	Augusta	Kansas	United States	67010
22	Heartland Research Associates, LLC	Newton	Kansas	United States	67114
23	Heartland Research Associates, LLC	Park City	Kansas	United States	67207
24	Heartland Research Associates, LLC	Wichita	Kansas	United States	67205
25	Heartland Research Associates, LLC	Wichita	Kansas	United States	67207
26	MedPharmics, LLC	Metairie	Louisiana	United States	70006
27	NECCR Primacare Research, LLC	Fall River	Massachusetts	United States	02721
28	Albuquerque Neuroscience, Inc.	Albuquerque	New Mexico	United States	87109
29	Radiant Research, Inc.	Jamaica	New York	United States	11432
30	PMG Research of Raleigh, Inc.	Raleigh	North Carolina	United States	27609
31	Wake Research Associates, LLC	Raleigh	North Carolina	United States	27612
32	PMG Research of Wilmington, LLC	Wilmington	North Carolina	United States	28401
33	Radiant Research, Inc.	Cincinnati	Ohio	United States	45236
34	Radiant Research, Inc.	Columbus	Ohio	United States	43212
35	Midwest Clinical Research Center	Dayton	Ohio	United States	45417
36	Neurology Diagnostics, Inc.	Dayton	Ohio	United States	45459
37	Aventiv Research, Inc.	Dublin	Ohio	United States	43016
38	Summit Research Network (Oregon), Inc.	Portland	Oregon	United States	97210
39	Oregon Center for Clinical Investigations, Inc	Salem	Oregon	United States	97301
40	Fieve Clinical Research, Inc.	Scranton	Pennsylvania	United States	18503
41	Radiant Research, Inc.	Anderson	South Carolina	United States	85282
42	Clinical Research Associates, Inc.	Nashville	Tennessee	United States	37203
43	Tekton Research	Austin	Texas	United States	78745
44	Ventavia Research Group	Fort Worth	Texas	United States	76104
45	Red Star Research	Lake Jackson	Texas	United States	77566
46	FMC Science	Lampasas	Texas	United States	76550
47	PCP for Life	Magnolia	Texas	United States	77355
48	Research Across America	Mesquite	Texas	United States	75149
49	Doctors of Internal Medicine, LTD / Radiant Research, Inc.	Plano	Texas	United States	75093
50	DM Clinical Research	Tomball	Texas	United States	77373

Sponsors and Collaborators

• Biohaven Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 23, 2018
• Statistical Analysis Plan - Jun 20, 2018

More Information

Publications

None provided.

• Responsible Party: Biohaven Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03237845
• Other Study ID Numbers: BHV3000-302
• First Posted: Aug 3, 2017
• Last Update Posted: Jan 22, 2021
• Last Verified: Dec 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Migraine Disorders

Study Results

Participant Flow

Recruitment Details	This study was conducted at 50 sites in United States of which 49 sites enrolled at least 1 participant.
Pre-assignment Detail	A total of 1499 participants were enrolled, of which 1186 participants were randomized to rimegepant 75 milligram (mg) or placebo. A total of 313 participants failed screening mainly due to failure to meet eligibility criteria. The randomization was stratified in a 1:1 ratio based on use of prophylactic migraine medications (yes or no).

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Period Title: Overall Study
STARTED	594	592
Treated	543	543
COMPLETED	538	542
NOT COMPLETED	56	50

Baseline Characteristics

Arm/Group Title	Rimegepant 75 mg	Placebo	Total
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Total of all reporting groups
Overall Participants	537	535	1072
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.195 (11.8693)	40.910 (12.1168)	40.552 (11.9932)
Sex: Female, Male (Count of Participants)
Female	479 89.2%	472 88.2%	951 88.7%
Male	58 10.8%	63 11.8%	121 11.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	77 14.3%	83 15.5%	160 14.9%
Not Hispanic or Latino	460 85.7%	452 84.5%	912 85.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 0.7%	5 0.9%	9 0.8%
Asian	8 1.5%	8 1.5%	16 1.5%
Native Hawaiian or Other Pacific Islander	6 1.1%	0 0%	6 0.6%
Black or African American	111 20.7%	118 22.1%	229 21.4%
White	394 73.4%	399 74.6%	793 74%
More than one race	14 2.6%	5 0.9%	19 1.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Primary Migraine Type (Count of Participants)
Migraine without Aura	355 66.1%	366 68.4%	721 67.3%
Migraine with Aura	182 33.9%	169 31.6%	351 32.7%
Randomization Strata, Prophylactic Migraine Medication Use (Count of Participants)
Yes	89 16.6%	89 16.6%	178 16.6%
No	448 83.4%	446 83.4%	894 83.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Freedom From Pain at 2 Hours Post-dose
Description	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic diary (eDiary). Pain freedom was defined as pain level of none.
Time Frame	2 Hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on modified intent to treat (mITT) participants.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	537	535
Number (95% Confidence Interval) [Percentage of participants]	19.6 3.6%	12.0 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	7.6
	Confidence Interval	(2-Sided) 95%; 3.3 to 11.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose
Description	MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at onset that was absent post-dose.
Time Frame	2 Hours

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	537	535
Number (95% Confidence Interval) [Percentage of Participants]	37.6 7%	25.2 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	12.4
	Confidence Interval	(2-Sided) 95%; 6.9 to 17.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose
Description	Photophobia (sensitivity to light) status was measured as absent or present in the eDiary. Freedom from photophobia was defined as photophobia absent.
Time Frame	2 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants with photophobia present at migraine onset.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	489	477
Number (95% Confidence Interval) [Percentage of Participants]	37.4 7%	22.3 4.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.1
	Confidence Interval	(2-Sided) 95%; 9.4 to 20.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose
Description	Phonophobia (sensitivity to sound) status was measured as absent or present in the eDiary. Freedom from phonophobia was defined as phonophobia absent.
Time Frame	2 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants with phonophobia present at migraine onset.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	362	374
Number (95% Confidence Interval) [Percentage of Participants]	36.7 6.8%	26.8 5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	9.9
	Confidence Interval	(2-Sided) 95%; 3.2 to 16.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With Pain Relief at 2 Hours Post-dose
Description	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild.
Time Frame	2 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants..

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	537	535
Number (95% Confidence Interval) [Percentage of Participants]	58.1 10.8%	42.8 8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.3
	Confidence Interval	(2-Sided) 95%; 9.4 to 21.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose
Description	Nausea status was measured as absent or present in the eDiary. Freedom from nausea was defined as nausea absent.
Time Frame	2 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants with nausea present at migraine onset.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	355	336
Number (95% Confidence Interval) [Percentage of Participants]	48.1 9%	43.3 8.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2084
	Comments	P-Value ≥ 0.05; therefore, all secondary outcome measures listed after this outcome measure in the hierarchy were not tested.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	4.8
	Confidence Interval	(2-Sided) 95%; -2.7 to 12.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose
Description	Participants who did not experience relief of their migraine headache at the end of 2 hours after dosing with study medication (and after the 2-hour assessments had been completed on the eDiary) were permitted to use the following rescue medications: aspirin, ibuprofen, acetaminophen up to 1000 mg/day (this includes Excedrin Migraine), naproxen (or any other type of nonsteroidal anti-inflammatory drug), antiemetics (e.g., metoclopramide or promethazine), or baclofen. The participant's use of rescue medication was recorded by the participant in a paper diary.
Time Frame	24 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	537	535
Number (95% Confidence Interval) [Percentage of Participants]	21.0 3.9%	37.0 6.9%

8. Secondary Outcome

Title	Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose
Description	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.
Time Frame	From 2 hours up to 24 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	537	535
Number (95% Confidence Interval) [Percentage of Participants]	12.3 2.3%	7.1 1.3%

9. Secondary Outcome

Title	Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose
Description	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.
Time Frame	From 2 hours up to 24 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	537	535
Number (95% Confidence Interval) [Percentage of Participants]	42.6 7.9%	26.5 5%

10. Secondary Outcome

Title	Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose
Description	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.
Time Frame	From 2 hours up to 48 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	537	535
Number (95% Confidence Interval) [Percentage of Participants]	9.9 1.8%	6.0 1.1%

11. Secondary Outcome

Title	Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose
Description	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.
Time Frame	From 2 hours up to 48 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	537	535
Number (95% Confidence Interval) [Percentage of Participants]	36.3 6.8%	22.6 4.2%

12. Secondary Outcome

Title	Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose
Description	Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relapse was defined as pain level of mild, moderate, or severe after 2 hours up to 48 hours for the participants who were pain-free at 2 hours post-dose.
Time Frame	From 2 hours up to 48 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis population was performed on mITT participants with pain freedom at 2 hours post-dose.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	105	64
Number (95% Confidence Interval) [Percentage of Participants]	49.6 9.2%	50.0 9.3%

13. Secondary Outcome

Title	Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose
Description	Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function.
Time Frame	2 hours post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	537	535
Number (95% Confidence Interval) [Percentage of Participants]	32.6 6.1%	23.4 4.4%

Adverse Events

Time Frame	Serious adverse events (SAEs) were collected from informed consent up to the end of the study, and adverse events (AEs) were collected from randomization up to end of the study (up to 52 days).
Adverse Event Reporting Description	The safety population, all enrolled participants who received at least 1 dose of rimegepant or placebo, was used to determine the number of participants at risk for SAEs and other AEs.
Arm/Group Title	Rimegepant 75 mg		Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant tablet on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.		Participants were administered a single oral dose of matching placebo tablet for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
All Cause Mortality
	Rimegepant 75 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/543 (0%)		0/543 (0%)
Serious Adverse Events
	Rimegepant 75 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/543 (0.2%)		2/543 (0.4%)
General disorders
Chest Pain	0/543 (0%)	0	1/543 (0.2%)	1
Infections and infestations
Urinary Tract Infection	0/543 (0%)	0	1/543 (0.2%)	1
Musculoskeletal and connective tissue disorders
Back Pain	1/543 (0.2%)	1	0/543 (0%)	0
Other (Not Including Serious) Adverse Events
	Rimegepant 75 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/543 (0%)		0/543 (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 trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.