Safety and Efficacy Study in Adult Subjects With Acute Migraines

• Sponsor: Biohaven Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03235479
• Collaborator: (none)
• Enrollment: 1,485
• Locations: 50
• Arms: 2
• Actual Duration (Months): 6.3
• Patients Per Site: 29.7
• Patients Per Site Per Month: 4.7

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: 1485 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: BHV3000-301: 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 18, 2017
• Actual Primary Completion Date: Jan 21, 2018
• Actual Study Completion Date: Jan 26, 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 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 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 mal-absorption

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, 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 patients who have met DSM-V criteria for any significant substance use disorder within the past 12 months from the date of the screening visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Research Associates, Inc	Birmingham	Alabama	United States	35205
2	Neurological Physicians of Arizona/Radiant Research Inc	Gilbert	Arizona	United States	85282
3	Clinical Research Consortium Arizona	Tempe	Arizona	United States	85283
4	Radiant Research, Inc.	Tucson	Arizona	United States	85712
5	Woodland International Research Group, LLC	Little Rock	Arkansas	United States	72211
6	Pharmacology Research Institute	Encino	California	United States	91316
7	Optimus Medical Group	San Francisco	California	United States	94102
8	California Medical Clinic for Headache	Santa Monica	California	United States	90404
9	Diablo Clinical Research, Inc	Walnut Creek	California	United States	94598
10	Qps Mra, Llc	Hollywood	Florida	United States	33024
11	Multi-Specialty Research Associates, Inc	Lake City	Florida	United States	32055
12	Qps Mra, Llc	Miami	Florida	United States	33143
13	Advanced Pharma CR, LLC	Miami	Florida	United States	33147
14	Compass Research, LLC	Orlando	Florida	United States	32806
15	Ormond Medical Arts Pharmaceutical Research	Ormond Beach	Florida	United States	32174
16	Meridian Clinical Research	Savannah	Georgia	United States	31406
17	New Orleans Center for Clinical Research	New Orleans	Louisiana	United States	70119
18	Boston Clinical Trials, Inc	Boston	Massachusetts	United States	02131
19	Milford Emergency Associates, Inc.	Marlborough	Massachusetts	United States	01752
20	Michigan Head Pain & Neurological Institute	Ann Arbor	Michigan	United States	48104
21	Clinical Research Institute, Inc	Minneapolis	Minnesota	United States	55402
22	Clinical Research Institute	Minneapolis	Minnesota	United States	55402
23	The Center for Pharmaceutical Research	Kansas City	Missouri	United States	64114
24	Sundance Clinical Research, LLC	Saint Louis	Missouri	United States	63141
25	Meridian Clinical Research -Norfolk	Norfolk	Nebraska	United States	68701
26	Meridian Clinical Research, LLC	Omaha	Nebraska	United States	68134
27	Clinical Research Consortium- Las Vegas	Las Vegas	Nevada	United States	89119
28	Hassman Research Institute, LLC	Berlin	New Jersey	United States	08009
29	SPRI Clinical Trials, LLC	Brooklyn	New York	United States	11235
30	Regional Clinical Research, Inc.	Endwell	New York	United States	13760
31	Central New York Clinical Research	Manlius	New York	United States	13104
32	Fieve Clinical Research	New York	New York	United States	10168
33	Rochester Clinical Research, Inc	Rochester	New York	United States	14609
34	PharmQuest, LLC	Greensboro	North Carolina	United States	27408
35	CTI Clinical Research Center	Cincinnati	Ohio	United States	45227
36	Oregon Center for Clinical Investigations, Inc	Portland	Oregon	United States	97214
37	Clinical Research of Philadelphia, LLC	Philadelphia	Pennsylvania	United States	19114-1029
38	Preferred Primary Care Physicians	Uniontown	Pennsylvania	United States	15401
39	Omega Medical Research	Warwick	Rhode Island	United States	02886
40	Coastal Carolina Research Center	Mount Pleasant	South Carolina	United States	29464
41	Meridian Clinical Research	Dakota Dunes	South Dakota	United States	57409
42	FutureSearch Trials of Neurology, LP	Austin	Texas	United States	78731
43	FutureSearch Trials of Neurology, LP	Dallas	Texas	United States	75231
44	Texas Center for Drug Development	Houston	Texas	United States	77081
45	J.Lewis Research Inc / Foothill Family Clinic South	Salt Lake City	Utah	United States	84121
46	J.Lewis Research Inc. / Jordan River Family Med	South Jordan	Utah	United States	84095
47	Clinical Research Associates of Tidewater, Inc.	Norfolk	Virginia	United States	23507
48	Tidewater Integrated Medical Research	Virginia Beach	Virginia	United States	23454
49	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
50	Seattle Women's:Health, Research & Gynecology	Seattle	Washington	United States	98105

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: NCT03235479
• Other Study ID Numbers: BHV-3000-301
• First Posted: Aug 1, 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	The study was conducted at 50 centers in the United States.
Pre-assignment Detail	A total of 1485 participants were enrolled, of which 1162 participants were randomized to BHV-3000 (rimegepant) 75 milligram (mg) or placebo. A total of 323 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 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 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	582	580
Treated	546	549
COMPLETED	541	540
NOT COMPLETED	41	40

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 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 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	543	541	1084
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.945 (12.3286)	41.326 (12.1381)	41.636 (12.2322)
Sex: Female, Male (Count of Participants)
Female	464 85.5%	463 85.6%	927 85.5%
Male	79 14.5%	78 14.4%	157 14.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	58 10.7%	68 12.6%	126 11.6%
Not Hispanic or Latino	485 89.3%	473 87.4%	958 88.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.2%	3 0.6%	4 0.4%
Asian	6 1.1%	7 1.3%	13 1.2%
Native Hawaiian or Other Pacific Islander	2 0.4%	0 0%	2 0.2%
Black or African American	107 19.7%	80 14.8%	187 17.3%
White	417 76.8%	444 82.1%	861 79.4%
More than one race	10 1.8%	7 1.3%	17 1.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Primary Migraine Type (Count of Participants)
Migraine without Aura	353 65%	358 66.2%	711 65.6%
Migraine with Aura	190 35%	183 33.8%	373 34.4%
Randomization Strata, Prophylactic Migraine Medication Use (Count of Participants)
Yes	90 16.6%	92 17%	182 16.8%
No	453 83.4%	449 83%	902 83.2%

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	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	543	541
Number (95% Confidence Interval) [percentage of participants]	19.2 3.5%	14.2 2.6%

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	0.0298
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	4.9
	Confidence Interval	(2-Sided) 95%; 0.5 to 9.3
	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	Placebo
Arm/Group Description	Participants were administered a single oral dose of 75 mg of rimegepant 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	543	541
Number (95% Confidence Interval) [percentage of participants]	36.6 6.7%	27.7 5.1%

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	0.0016
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	8.9
	Confidence Interval	(2-Sided) 95%; 3.4 to 14.4
	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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	470	483
Number (95% Confidence Interval) [percentage of participants]	34.9 6.4%	24.8 4.6%

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	0.0005
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	10.2
	Confidence Interval	(2-Sided) 95%; 4.4 to 15.9
	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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	345	366
Number (95% Confidence Interval) [percentage of participants]	38.6 7.1%	30.9 5.7%

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	0.0299
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; 0.8 to 14.6
	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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	543	541
Number (95% Confidence Interval) [percentage of participants]	56.0 10.3%	45.7 8.4%

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	10.3
	Confidence Interval	(2-Sided) 95%; 4.4 to 16.2
	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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	318	322
Number (95% Confidence Interval) [percentage of participants]	46.9 8.6%	41.6 7.7%

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	0.1815
	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	5.2
	Confidence Interval	(2-Sided) 95%; -2.4 to 12.9
	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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	543	541
Number (95% Confidence Interval) [percentage of participants]	20.4 3.8%	31.8 5.9%

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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	543	541
Number (95% Confidence Interval) [percentage of participants]	14.0 2.6%	8.1 1.5%

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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	543	541
Number (95% Confidence Interval) [percentage of participants]	38.9 7.2%	27.9 5.2%

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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	543	541
Number (95% Confidence Interval) [percentage of participants]	11.6 2.1%	7.2 1.3%

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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	543	541
Number (95% Confidence Interval) [percentage of participants]	33.7 6.2%	23.9 4.4%

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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	104	77
Number (95% Confidence Interval) [percentage of participants]	40.1 7.4%	50.0 9.2%

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 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 for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization.
Measure Participants	543	541
Number (95% Confidence Interval) [percentage of participants]	33.3 6.1%	21.8 4%

Adverse Events

Time Frame	Serious adverse events (SAEs) were collected from informed consent up to the end of study, and adverse events (AEs) were collected from randomization up to the 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 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 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	0/546 (0%)		0/549 (0%)
Serious Adverse Events
	Rimegepant 75 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/546 (0.4%)		1/549 (0.2%)
Gastrointestinal disorders
Colitis	0/546 (0%)	0	1/549 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/546 (0.2%)	1	0/549 (0%)	0
Pulmonary Embolism	1/546 (0.2%)	1	0/549 (0%)	0
Other (Not Including Serious) Adverse Events
	Rimegepant 75 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/546 (0%)		0/549 (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.