Trial Outcomes & Findings for Safety and Efficacy Study in Adult Subjects With Acute Migraines (NCT NCT03235479)

NCT ID: NCT03235479

Last Updated: 2023-02-16

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1485 participants
• Primary outcome timeframe: 2 hours post-dose
• Results posted on: 2023-02-16

Participant Flow

The study was conducted at 50 centers in the United States.

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).

Participant milestones

Measure	Rimegepant 75 mg 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.	Placebo 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.
Overall Study STARTED	582	580
Overall Study Treated	546	549
Overall Study COMPLETED	541	540
Overall Study NOT COMPLETED	41	40

Reasons for withdrawal

Measure	Rimegepant 75 mg 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.	Placebo 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.
Overall Study Lost to Follow-up	8	11
Overall Study Not Experienced Moderate/Severe Migraine	23	17
Overall Study Pregnancy	1	0
Overall Study Protocol Deviation	1	3
Overall Study Technical Problems	3	2
Overall Study Withdrawal by Subject	2	2
Overall Study Other Reasons	3	5

Baseline Characteristics

Safety and Efficacy Study in Adult Subjects With Acute Migraines

Baseline characteristics by cohort

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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 n=1084 Participants Total of all reporting groups
Age, Continuous	41.945 years STANDARD_DEVIATION 12.3286 • n=5 Participants	41.326 years STANDARD_DEVIATION 12.1381 • n=7 Participants	41.636 years STANDARD_DEVIATION 12.2322 • n=5 Participants
Sex: Female, Male Female	464 Participants n=5 Participants	463 Participants n=7 Participants	927 Participants n=5 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	78 Participants n=7 Participants	157 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	58 Participants n=5 Participants	68 Participants n=7 Participants	126 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	485 Participants n=5 Participants	473 Participants n=7 Participants	958 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	107 Participants n=5 Participants	80 Participants n=7 Participants	187 Participants n=5 Participants
Race (NIH/OMB) White	417 Participants n=5 Participants	444 Participants n=7 Participants	861 Participants n=5 Participants
Race (NIH/OMB) More than one race	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Primary Migraine Type Migraine without Aura	353 Participants n=5 Participants	358 Participants n=7 Participants	711 Participants n=5 Participants
Primary Migraine Type Migraine with Aura	190 Participants n=5 Participants	183 Participants n=7 Participants	373 Participants n=5 Participants
Randomization Strata, Prophylactic Migraine Medication Use Yes	90 Participants n=5 Participants	92 Participants n=7 Participants	182 Participants n=5 Participants
Randomization Strata, Prophylactic Migraine Medication Use No	453 Participants n=5 Participants	449 Participants n=7 Participants	902 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 hours post-dose

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

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.

Outcome measures

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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.
Percentage of Participants With Freedom From Pain at 2 Hours Post-dose	19.2 percentage of participants Interval 15.8 to 22.5	14.2 percentage of participants Interval 11.3 to 17.2

PRIMARY outcome

Timeframe: 2 hours post-dose

Population: The analysis was performed on mITT participants.

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.

Outcome measures

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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.
Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose	36.6 percentage of participants Interval 32.6 to 40.7	27.7 percentage of participants Interval 24.0 to 31.5

SECONDARY outcome

Timeframe: 2 hours post-dose

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

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

Outcome measures

Measure	Rimegepant 75 mg n=470 Participants 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.	Placebo n=483 Participants 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.
Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose	34.9 percentage of participants Interval 30.6 to 39.2	24.8 percentage of participants Interval 20.9 to 28.6

SECONDARY outcome

Timeframe: 2 hours post-dose

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

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

Outcome measures

Measure	Rimegepant 75 mg n=345 Participants 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.	Placebo n=366 Participants 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.
Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose	38.6 percentage of participants Interval 33.4 to 43.7	30.9 percentage of participants Interval 26.2 to 35.5

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: The analysis was performed on mITT participants.

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.

Outcome measures

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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.
Percentage of Participants With Pain Relief at 2 Hours Post-dose	56.0 percentage of participants Interval 51.8 to 60.2	45.7 percentage of participants Interval 41.5 to 49.9

SECONDARY outcome

Timeframe: 2 hours post-dose

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

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

Outcome measures

Measure	Rimegepant 75 mg n=318 Participants 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.	Placebo n=322 Participants 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.
Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose	46.9 percentage of participants Interval 41.4 to 52.3	41.6 percentage of participants Interval 36.2 to 47.0

SECONDARY outcome

Timeframe: 24 hours post-dose

Population: The analysis was performed on mITT participants.

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.

Outcome measures

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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.
Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose	20.4 percentage of participants Interval 17.1 to 23.8	31.8 percentage of participants Interval 27.9 to 35.6

SECONDARY outcome

Timeframe: From 2 hours up to 24 hours post-dose

Population: The analysis was performed on mITT participants.

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.

Outcome measures

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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.
Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose	14.0 percentage of participants Interval 11.1 to 16.9	8.1 percentage of participants Interval 5.8 to 10.4

SECONDARY outcome

Timeframe: From 2 hours up to 24 hours post-dose

Population: The analysis was performed on mITT participants.

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.

Outcome measures

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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.
Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose	38.9 percentage of participants Interval 34.8 to 43.0	27.9 percentage of participants Interval 24.2 to 31.7

SECONDARY outcome

Timeframe: From 2 hours up to 48 hours post-dose

Population: The analysis was performed on mITT participants.

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.

Outcome measures

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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.
Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose	11.6 percentage of participants Interval 8.9 to 14.3	7.2 percentage of participants Interval 5.0 to 9.4

SECONDARY outcome

Timeframe: From 2 hours up to 48 hours post-dose

Population: The analysis was performed on mITT participants.

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.

Outcome measures

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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.
Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose	33.7 percentage of participants Interval 29.7 to 37.7	23.9 percentage of participants Interval 20.3 to 27.4

SECONDARY outcome

Timeframe: From 2 hours up to 48 hours post-dose

Population: The analysis population was performed on mITT participants with pain freedom at 2 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.

Outcome measures

Measure	Rimegepant 75 mg n=104 Participants 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.	Placebo n=77 Participants 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.
Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose	40.1 percentage of participants Interval 30.6 to 49.6	50.0 percentage of participants Interval 39.0 to 61.0

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: The analysis was performed on mITT participants.

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.

Outcome measures

Measure	Rimegepant 75 mg n=543 Participants 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.	Placebo n=541 Participants 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.
Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose	33.3 percentage of participants Interval 29.4 to 37.3	21.8 percentage of participants Interval 18.4 to 25.3

Adverse Events

Rimegepant 75 mg

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rimegepant 75 mg n=546 participants at risk 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.	Placebo n=549 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.18% 1/546 • Number of events 1 • 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). 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.	0.00% 0/549 • 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). 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.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.18% 1/546 • Number of events 1 • 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). 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.	0.00% 0/549 • 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). 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.
Gastrointestinal disorders Colitis	0.00% 0/546 • 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). 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.	0.18% 1/549 • Number of events 1 • 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). 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.

Other adverse events

Adverse event data not reported

Additional Information

Chief Medical Officer

Biohaven Pharmaceuticals, Inc.

Phone: 203-404-0410

Email: clinicaltrials@biohavenpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60