Trial in Adult Subjects With Acute Migraines

• Sponsor: Biohaven Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03461757
• Collaborator: (none)
• Enrollment: 1,811
• Locations: 69
• Arms: 2
• Actual Duration (Months): 7.6
• Patients Per Site: 26.2
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of BHV-3000 (rimegepant ODT) 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: 1811 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: BHV3000-303: Phase 3, Double-Blind, Randomized, Placebo Controlled, Safety and Efficacy Trial of BHV-3000 (Rimegepant) Orally Disintegrating Tablet (ODT) for the Acute Treatment of Migraine
• Actual Study Start Date: Feb 27, 2018
• Actual Primary Completion Date: Oct 8, 2018
• Actual Study Completion Date: Oct 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Rimegepant 75 mg Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Drug: Rimegepant; 75 mg ODT QD; Other Names: BHV-3000
Placebo Comparator: Arm 2: Placebo Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Drug: Placebo; Placebo ODT 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 post-dose]

   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 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.

2. 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.

3. 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.

4. Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 24 Hours Post-dose [From 2 hours up to 24 hours post-dose]

   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. Sustained freedom was defined as MBS reported at onset that was absent at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.

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 Freedom From Functional Disability From 2 to 24 Hours Post-dose [From 2 hours up to 24 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. Sustained freedom from functional disability was defined as normal function 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 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.

8. Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 48 Hours Post-dose [From 2 hours up to 48 hours post-dose]

   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. Sustained freedom was defined as MBS reported at onset that was absent 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 Freedom From Functional Disability From 2 to 48 Hours Post-dose [From 2 hours up to 48 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. Sustained freedom from functional disability was defined as normal function at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.

10. 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.

11. Percentage of Participants With Freedom From Functional Disability at 90 Minutes Post-dose [90 minutes 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.

12. Percentage of Participants With Pain Relief at 90 Minutes Post-dose [90 minutes 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.

13. 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.

14. Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 90 Minutes Post-dose [90 minutes post dose]

    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.

15. Percentage of Participants With Freedom From Pain at 90 Minutes Post-dose [90 minutes 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.

16. 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.

17. 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.

18. Percentage of Participants With Pain Relief at 60 Minutes Post-dose [60 minutes 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.

19. Percentage of Participants With Freedom From Functional Disability at 60 Minutes Post-dose [60 minutes 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.

20. 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.

21. 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 post-dose for the participants who were pain-free at 2 hours post-dose.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

1. Subject 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:

1. Migraine attacks present for more than 1 year with the age of onset prior to 50 years of age

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

3. Not more than 8 attacks of moderate to severe intensity per month within the last 3 months

4. 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

5. 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.

6. Subjects 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 screening visit and the dose is not expected to change during the course of the study.

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

Key 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 being enrolled)

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

5. 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

6. The subject has a history of current or evidence of any significant and/ or unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known 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.

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

8. Subjects are excluded if they have previously participated in any BHV-30000 (rimegepant) study within the last 2 years.

9. Participation in any other investigational clinical trial while participating in this clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Coastal Clinical Research, LLC	Mobile	Alabama	United States	36608
2	Clinical Research Consortium, An AMR Company	Tempe	Arizona	United States	85283
3	Radiant Research, Inc.	Tucson	Arizona	United States	85712
4	Baptist Health Center for Clinical Research	Little Rock	Arkansas	United States	72205
5	Woodland International Research Group, LLC	Little Rock	Arkansas	United States	72211
6	Pharmacology Research Institute	Encino	California	United States	91316
7	eStudySite	La Mesa	California	United States	91942
8	Collaborative Neuroscience Network, LLC	Long Beach	California	United States	90806
9	Pharmacology Research Institute	Los Alamitos	California	United States	90720
10	Synergy San Diego	National City	California	United States	91950
11	Pharmacology Research Institute	Newport Beach	California	United States	92660
12	Optimus Medical Group	San Francisco	California	United States	94102
13	Diablo Clinical Research, Inc.	Walnut Creek	California	United States	94598
14	Yale University	New Haven	Connecticut	United States	06519
15	Ki Health Partners LLC DBA New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
16	MD Clinical	Hallandale Beach	Florida	United States	33009
17	AGA Clinical Trials	Hialeah	Florida	United States	33012
18	Multi-Specialty Research Associates, Inc.	Lake City	Florida	United States	32055
19	Qps Mra, Llc	Miami	Florida	United States	33143
20	Clinical Neuroscience Solutions, Inc	Orlando	Florida	United States	32801
21	Ormond Medical Arts Pharmaceutical Research	Ormond Beach	Florida	United States	32174
22	Synexus	Atlanta	Georgia	United States	30328
23	iResearch Atlanta, LLC	Decatur	Georgia	United States	30030
24	Meridian Clinical Research, LLC	Savannah	Georgia	United States	31406
25	Heartland Research Associates LLC	Augusta	Kansas	United States	67010
26	Heartland Research Associates, LLC	Wichita	Kansas	United States	67205
27	Cresent City Headache and Neurology Center LLC	Chalmette	Louisiana	United States	70043
28	New Orleans Center for Clinical Research	New Orleans	Louisiana	United States	70119
29	DelRicht Research	New Orleans	Louisiana	United States	70124
30	Boston Clinical Trials	Boston	Massachusetts	United States	02131
31	NECCR Primacare Research, LLC	Fall River	Massachusetts	United States	02721
32	Community Clinical Research Network/Milford Emergency Associates, Inc	Marlborough	Massachusetts	United States	01752
33	Clinical Research Institute, Inc.	Minneapolis	Minnesota	United States	55042
34	Clinical Research Institute, Inc.	Plymouth	Minnesota	United States	55441
35	Center for Pharmaceutical Research	Kansas City	Missouri	United States	64114
36	Sundance Clinical Research	Saint Louis	Missouri	United States	63141
37	StudyMetrix Research, LLC	Saint Peters	Missouri	United States	63303
38	Meridian Clinical Research, LLC	Norfolk	Nebraska	United States	68701
39	Hassman Research Institute	Berlin	New Jersey	United States	08009
40	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico	United States	87102
41	SPRI Clinical Trials, LLC	Brooklyn	New York	United States	11235
42	CNS Research Science, Inc.	Jamaica	New York	United States	11432
43	Rochester Clinical Research, Inc.	Rochester	New York	United States	14609
44	PharmQuest, LLC	Greensboro	North Carolina	United States	27408
45	PMG Research of Raleigh	Raleigh	North Carolina	United States	27609
46	Wilmington Health, PLLC	Wilmington	North Carolina	United States	28401
47	Radiant Research, Inc.	Columbus	Ohio	United States	43212
48	Midwest Clinical Research Center	Dayton	Ohio	United States	45417
49	Hometown Urgent Care and Research	Dayton	Ohio	United States	45424
50	Neurology Diagnostics, Inc.	Dayton	Ohio	United States	45459
51	Aventiv Research Inc	Dublin	Ohio	United States	43016
52	Summit Research Network (Oregon) Inc.	Portland	Oregon	United States	97210
53	Clinical Research of Philadelphia, LLC	Philadelphia	Pennsylvania	United States	19114
54	Coastal Carolina Research	Mount Pleasant	South Carolina	United States	29464
55	Meridian Clinical Research	Dakota Dunes	South Dakota	United States	57049
56	Volunteer Research Group	Knoxville	Tennessee	United States	37920
57	Clinical Research Institute, Inc.	Nashville	Tennessee	United States	37203
58	Nashville Neuroscience Group	Nashville	Tennessee	United States	37203
59	Tekton Research, Inc	Austin	Texas	United States	78745
60	FutureSearch Trials of Dallas, LP	Dallas	Texas	United States	75231
61	Ventavia Research Group, LLC	Fort Worth	Texas	United States	76104
62	Texas Center for Drug Development, Inc.	Houston	Texas	United States	77081
63	Red Star Research	Lake Jackson	Texas	United States	77566
64	DM Clinical Research	Tomball	Texas	United States	77375
65	Charlottesville Medical Research	Charlottesville	Virginia	United States	22911
66	Tidewater Integrated Medical Research	Virginia Beach	Virginia	United States	23454
67	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
68	Seattle Women's: Health, Research, Gynecology	Seattle	Washington	United States	98105
69	Clinical Investigation Specialists, Inc.	Kenosha	Wisconsin	United States	53144

Sponsors and Collaborators

• Biohaven Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 23, 2018
• Statistical Analysis Plan - Nov 15, 2018

More Information

Publications

None provided.

• Responsible Party: Biohaven Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03461757
• Other Study ID Numbers: BHV3000-303
• First Posted: Mar 12, 2018
• Last Update Posted: Mar 27, 2020
• Last Verified: Mar 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	The study was conducted at 69 centers in the United States.
Pre-assignment Detail	Total 1811 participants were enrolled, of which 1466 were randomized to rimegepant 75 milligram (mg) orally disintegrating tablet (ODT) or placebo. Total 345 participants failed screening mainly due to failure to meet eligibility criteria. Randomization was stratified in 1:1 ratio based on use of prophylactic migraine medications (yes or no).

Arm/Group Title	Rimegepant 75 mg ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Period Title: Overall Study
STARTED	732	734
Treated	682	693
COMPLETED	679	689
NOT COMPLETED	53	45

Baseline Characteristics

Arm/Group Title	Rimegepant 75 mg ODT	Placebo	Total
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Total of all reporting groups
Overall Participants	669	682	1351
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.287 (12.0792)	40.030 (11.8719)	40.157 (11.9713)
Sex: Female, Male (Count of Participants)
Female	568 84.9%	579 84.9%	1147 84.9%
Male	101 15.1%	103 15.1%	204 15.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	116 17.3%	135 19.8%	251 18.6%
Not Hispanic or Latino	553 82.7%	547 80.2%	1100 81.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 0.6%	3 0.4%	7 0.5%
Asian	8 1.2%	19 2.8%	27 2%
Native Hawaiian or Other Pacific Islander	141 21.1%	125 18.3%	266 19.7%
Black or African American	11 1.6%	5 0.7%	16 1.2%
White	496 74.1%	521 76.4%	1017 75.3%
More than one race	7 1%	9 1.3%	16 1.2%
Unknown or Not Reported	2 0.3%	0 0%	2 0.1%
Primary Migraine Type (Count of Participants)
Migraine without Aura	480 71.7%	462 67.7%	942 69.7%
Migraine with Aura	189 28.3%	220 32.3%	409 30.3%
Randomization Strata, Prophylactic Migraine Medication Use (Count of Participants)
Yes	93 13.9%	94 13.8%	187 13.8%
No	576 86.1%	588 86.2%	1164 86.2%

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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	21.2 3.2%	10.9 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	10.4
	Confidence Interval	(2-Sided) 95%; 6.5 to 14.2
	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 post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	35.1 5.2%	26.8 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	8.3
	Confidence Interval	(2-Sided) 95%; 3.4 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	59.3 8.9%	43.3 6.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	16.1
	Confidence Interval	(2-Sided) 95%; 10.8 to 21.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	38.1 5.7%	25.8 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	20.1
	Confidence Interval	(2-Sided) 95%; 15.1 to 25.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	47.8 7.1%	27.7 4.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	20.1
	Confidence Interval	(2-Sided) 95%; 15.1 to 25.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 24 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. Sustained freedom was defined as MBS reported at onset that was absent 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	27.1 4.1%	17.7 2.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	9.3
	Confidence Interval	(2-Sided) 95%; 4.9 to 13.7
	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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	14.2 2.1%	29.2 4.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	-15.0
	Confidence Interval	(2-Sided) 95%; -19.3 to -10.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 24 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. Sustained freedom from functional disability was defined as normal function 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	29.6 4.4%	16.9 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	12.7
	Confidence Interval	(2-Sided) 95%; 8.3 to 17.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	42.2 6.3%	25.2 3.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	16.9
	Confidence Interval	(2-Sided) 95%; 12.0 to 21.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 48 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. Sustained freedom was defined as MBS reported at onset that was absent 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	23.2 3.5%	16.4 2.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.8
	Confidence Interval	(2-Sided) 95%; 2.5 to 11.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 48 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. Sustained freedom from functional disability was defined as normal function 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	26.0 3.9%	15.4 2.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	10.6
	Confidence Interval	(2-Sided) 95%; 6.3 to 14.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	593	611
Number (95% Confidence Interval) [percentage of participants]	33.4 5%	24.5 3.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	8.8
	Confidence Interval	(2-Sided) 95%; 3.7 to 13.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Participants With Freedom From Functional Disability at 90 Minutes 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	90 minutes post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	30.2 4.5%	21.3 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	8.9
	Confidence Interval	(2-Sided) 95%; 4.3 to 13.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Participants With Pain Relief at 90 Minutes 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	90 minutes post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	49.6 7.4%	37.2 5.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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%; 7.1 to 17.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	15.7 2.3%	5.6 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	10.1
	Confidence Interval	(2-Sided) 95%; 6.9 to 13.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 90 Minutes 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	90 minutes post dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	27.4 4.1%	21.5 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0128
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.8
	Confidence Interval	(2-Sided) 95%; 1.2 to 10.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Percentage of Participants With Freedom From Pain at 90 Minutes 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	90 minutes post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	15.1 2.3%	7.3 1.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	7.8
	Confidence Interval	(2-Sided) 95%; 4.4 to 11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	451	447
Number (95% Confidence Interval) [percentage of participants]	41.7 6.2%	30.2 4.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.5
	Confidence Interval	(2-Sided) 95%; 5.3 to 17.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	13.5 2%	5.4 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, 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	8.0
	Confidence Interval	(2-Sided) 95%; 4.9 to 11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Percentage of Participants With Pain Relief at 60 Minutes 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	60 minutes post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	36.8 5.5%	31.2 4.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0314
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.5
	Confidence Interval	(2-Sided) 95%; 0.5 to 10.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Percentage of Participants With Freedom From Functional Disability at 60 Minutes 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	60 minutes post-dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on mITT participants.

Arm/Group Title	Rimegepant 75 mg ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	669	682
Number (95% Confidence Interval) [percentage of participants]	22.3 3.3%	15.8 2.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.4
	Confidence Interval	(2-Sided) 95%; 2.3 to 10.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	397	430
Number (95% Confidence Interval) [percentage of participants]	51.0 7.6%	45.2 6.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rimegepant 75 mg ODT, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0898
	Comments	P-Value ≥ 0.05; therefore, all secondary endpoints listed after this endpoint in the hierarchy were not tested.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 95%; -0.9 to 12.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. 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 post-dose 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 ODT	Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.	Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	142	74
Number (95% Confidence Interval) [percentage of participants]	36.6 5.5%	50.0 7.3%

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 ODT		Placebo
Arm/Group Description	Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.		Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
All Cause Mortality
	Rimegepant 75 mg ODT		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/682 (0%)		0/693 (0%)
Serious Adverse Events
	Rimegepant 75 mg ODT		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/682 (0%)		0/693 (0%)
Other (Not Including Serious) Adverse Events
	Rimegepant 75 mg ODT		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/682 (0%)		0/693 (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.