Trial Outcomes & Findings for Efficacy and Safety Study of Rimegepant for the Acute Treatment of Migraine in Japanese Subjects (Japan Only) (NCT NCT05399459)

NCT ID: NCT05399459

Last Updated: 2025-03-07

Results Overview

Pain freedom at 2 hours post-dose was defined as having a pain intensity of none at that time point. Pain was measured on a 4-point Likert scale, with following scores: 0= none, 1= mild, 2= moderate, 3= severe. Participants with score of 0 (no pain) were considered to have freedom from pain. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in Statistical Analysis Plan (SAP).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 897 participants
• Primary outcome timeframe: 2 hours post-dose
• Results posted on: 2025-03-07

Participant Flow

Out of 897 enrolled participants, 803 were randomized to receive study treatment.

Participant milestones

Measure	Rimegepant 25 mg Participants were randomized to receive orally disintegrated tablet (ODT) of rimegepant 25 milligram (mg) and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Overall Study STARTED	267	268	268
Overall Study Efficacy Analysis Set (As Randomized)	238	238	230
Overall Study Safety Analysis Set (As Treated)	239	238	229
Overall Study COMPLETED	237	238	230
Overall Study NOT COMPLETED	30	30	38

Reasons for withdrawal

Measure	Rimegepant 25 mg Participants were randomized to receive orally disintegrated tablet (ODT) of rimegepant 25 milligram (mg) and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Overall Study Randomized but not treated	29	30	38
Overall Study Lost to Follow-up	1	0	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Rimegepant 25 mg n=239 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Total n=706 Participants Total of all reporting groups	Placebo n=229 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Age, Continuous	40.3 Years STANDARD_DEVIATION 10.49 • n=239 Participants	40.5 Years STANDARD_DEVIATION 11.25 • n=238 Participants	40.8 Years STANDARD_DEVIATION 10.99 • n=706 Participants	41.4 Years STANDARD_DEVIATION 11.25 • n=229 Participants
Sex: Female, Male Female	188 Participants n=239 Participants	189 Participants n=238 Participants	550 Participants n=706 Participants	173 Participants n=229 Participants
Sex: Female, Male Male	51 Participants n=239 Participants	49 Participants n=238 Participants	156 Participants n=706 Participants	56 Participants n=229 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.	—

PRIMARY outcome

Timeframe: 2 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data.

Pain freedom at 2 hours post-dose was defined as having a pain intensity of none at that time point. Pain was measured on a 4-point Likert scale, with following scores: 0= none, 1= mild, 2= moderate, 3= severe. Participants with score of 0 (no pain) were considered to have freedom from pain. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in Statistical Analysis Plan (SAP).

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=230 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants Who Had Freedom From Pain at 2 Hours Post-Dose	21.0 Percentage of participants Interval 15.8 to 26.2	32.4 Percentage of participants Interval 26.4 to 38.3	13.0 Percentage of participants Interval 8.7 to 17.4

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data.

Pain relief at 2 hours post-dose was defined as a pain intensity of none or mild at that time point. Pain was measured on a 4-point Likert scale, with following scores: 0= none, 1= mild, 2= moderate, 3= severe. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=230 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Pain Relief at 2 Hours Post-Dose	66.8 Percentage of participants Interval 60.8 to 72.8	79.0 Percentage of participants Interval 73.8 to 84.2	56.5 Percentage of participants Interval 50.1 to 62.9

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data.

MBS freedom was defined as MBS reported before dosing that was absent post-dose. MBS included nausea, photophobia, or phonophobia. MBS were measured using a binary scale as 0= absent, 1= present. Participants who had score of 0 (MBS absent) were considered to have freedom from MBS. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=230 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants Who Had Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-Dose	53.4 Percentage of participants Interval 47.0 to 59.7	65.1 Percentage of participants Interval 59.1 to 71.2	50.4 Percentage of participants Interval 44.0 to 56.9

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data. Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Functional disability was defined as a functional disability level of mildly impaired, severely impaired, or required bedrest. Participants rated the level of disability they perceived as a result of their migraine in performing normal actions using following level of severity: normal function, mild impairment, severe impairment, or required bedrest. Percentage of participants with a response of "normal function" at the 2 hours post-dose were reported in this outcome measure. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=236 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=231 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=223 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Ability to Function Normally at 2 Hours Post-Dose	36.0 Percentage of participants Interval 29.9 to 42.1	45.5 Percentage of participants Interval 39.0 to 51.9	26.9 Percentage of participants Interval 21.1 to 32.7

SECONDARY outcome

Timeframe: 2 to 24 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data.

Sustained Pain relief from 2 to 24 hours post-dose was defined as a pain intensity of none or mild at all time points from 2 to 24 hours post-dose. Pain was measured on a 4-point Likert scale, with following scores: 0= none, 1= mild, 2= moderate, 3= severe. Participants with score of 0 (with no pain) through 2 to 24 hours post-dose were considered to have sustained pain relief. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=230 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-Dose	48.3 Percentage of participants Interval 42.0 to 54.7	63.4 Percentage of participants Interval 57.3 to 69.6	31.7 Percentage of participants Interval 25.7 to 37.8

SECONDARY outcome

Timeframe: Within 24 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took study drug, had migraine of moderate or severe pain intensity at time of treatment and had post-dose efficacy data. Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Percentage of participants who used rescue medications within 24 hours of administration of study drug were reported in this outcome measure. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=229 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants Who Used Rescue Medication Within 24 Hours Post-Dose	25.2 Percentage of participants Interval 19.7 to 30.7	19.7 Percentage of participants Interval 14.7 to 24.8	39.3 Percentage of participants Interval 33.0 to 45.6

SECONDARY outcome

Timeframe: 2 to 48 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data.

Sustained pain relief from 2 to 48 hours post-dose was defined as a pain intensity of none or mild at all time points from 2 to 48 hours post-dose. Pain was measured on a 4-point Likert scale, with following scores: 0= none, 1= mild, 2= moderate, 3= severe. Participants with score of 0 (with no pain) through 2 to 48 hours post-dose were considered to have sustained pain relief. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=230 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-Dose	42.0 Percentage of participants Interval 35.7 to 48.3	60.5 Percentage of participants Interval 54.3 to 66.7	27.4 Percentage of participants Interval 21.6 to 33.2

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data. Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Photophobia (sensitivity to light) status was measured as absent or present in the electronic diary (eDiary). Freedom from photophobia was defined as photophobia absent. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=162 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=159 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=153 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Absence of Photophobia at 2 Hours Post-Dose	45.1 Percentage of participants Interval 37.4 to 52.7	59.1 Percentage of participants Interval 51.5 to 66.8	49.0 Percentage of participants Interval 41.1 to 56.9

SECONDARY outcome

Timeframe: 2 to 24 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data.

Sustained pain freedom from 2 to 24 hours post-dose was defined as a pain intensity of none at all time points from 2 to 24 hours post-dose. Pain was measured on a 4-point Likert scale, with following scores: 0= none, 1= mild, 2= moderate, 3= severe. Participants with score of 0 (with no pain) through 2 to 24 hours post-dose were considered to have sustained pain freedom. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=230 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-Dose	13.9 Percentage of participants Interval 9.5 to 18.3	23.1 Percentage of participants Interval 17.8 to 28.5	6.5 Percentage of participants Interval 3.3 to 9.7

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data. Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Phonophobia (sensitivity to sound) status was measured as absent or present in the eDiary. Freedom from phonophobia was defined as phonophobia absent. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=131 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=108 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=108 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Freedom of Phonophobia at 2 Hours Post-Dose	55.0 Percentage of participants Interval 46.4 to 63.5	66.7 Percentage of participants Interval 57.8 to 75.6	50.0 Percentage of participants Interval 40.6 to 59.4

SECONDARY outcome

Timeframe: 2 to 48 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data.

Sustained pain freedom from 2 to 48 hours post-dose was defined as a pain intensity of none at all time points from 2 to 48 hours post-dose. Pain was measured on a 4-point Likert scale, with following scores: 0= none, 1= mild, 2= moderate, 3= severe. Participants with score of 0 (with no pain) through 2 to 48 hours post-dose were considered to have sustained pain freedom. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=230 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-Dose	11.8 Percentage of participants Interval 7.7 to 15.9	21.4 Percentage of participants Interval 16.2 to 26.6	6.1 Percentage of participants Interval 3.0 to 9.2

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data. Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Nausea status was measured as absent or present in the eDiary. Freedom from nausea was defined as nausea absent. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=98 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=99 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=91 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Freedom From Nausea at 2 Hours Post Dose	68.4 Percentage of participants Interval 59.2 to 77.6	73.7 Percentage of participants Interval 65.1 to 82.4	62.6 Percentage of participants Interval 52.7 to 72.6

SECONDARY outcome

Timeframe: 2 to 48 hours post-dose

Population: Efficacy analysis set consisted of all participants in the full analysis set who were randomized only once, took the study drug, had a migraine of moderate or severe pain intensity at the time of treatment, and had post-dose efficacy data. Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Pain relapse from 2 to 48 hours post-dose was defined as pain intensity of mild, moderate, or severe at any time point post-dose after 2 hours post-dose for the subset of participants with pain intensity of none at 2 hours post-dose. Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Formal statistical hypothesis testing was planned only for rimegepant 75 mg group with controlling type 1 error by the prespecified hierarchical gate-keeping procedure. For rimegepant 25 mg, no formal statistical hypothesis testing was conducted for any outcome measures as pre-specified in SAP.

Outcome measures

Measure	Rimegepant 25 mg n=50 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=77 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=30 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-Dose	44.0 Percentage of participants Interval 30.2 to 57.8	33.8 Percentage of participants Interval 23.2 to 44.3	53.3 Percentage of participants Interval 35.5 to 71.2

SECONDARY outcome

Timeframe: From the day of signing informed consent up to end of treatment visit (approximately maximum up to 11 weeks)

Population: Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo).

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participants or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with the treatment. AE intensity included mild, moderate and severe. Mild AE is defined as AEs which is usually transient and may require only minimal treatment or therapeutic intervention. The event were not generally interfered with usual activities of daily living. Moderate AE is defined as AEs which is usually alleviated with additional specific therapeutic intervention. The event interfered with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the participants. Severe AE is defined as AE that interrupts with usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.

Outcome measures

Measure	Rimegepant 25 mg n=239 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=229 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Number of Participants With Adverse Events (AEs) by Intensity Mild	16 Participants	19 Participants	12 Participants
Number of Participants With Adverse Events (AEs) by Intensity Moderate	1 Participants	3 Participants	3 Participants
Number of Participants With Adverse Events (AEs) by Intensity Severe	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From the day of signing informed consent up to end of treatment visit (approximately maximum up to 11 weeks)

Population: Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo).

A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect in the off spring who received rimegepant were considered an important medical event.

Outcome measures

Measure	Rimegepant 25 mg n=239 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=229 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Number of Participants With Serious AEs	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) up to End of treatment visit (within 7 days of treatment) [approximately maximum up to 7 weeks]

Population: Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo). Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Laboratory test abnormalities in hematology included: Eosinophils, Hemoglobin (high, low), Lymphocytes (high, low), Neutrophils, Platelets, White blood cell count (high, low). Laboratory abnormality events were graded according to National Cancer Institute Common Terminology Criteria For Adverse Events (NCI CTCAE) v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Number of participants who had hematology parameter abnormality Grade 3 to 4 are reported in this outcome measure. Number of participants with non-zero laboratory abnormalities were reported in this outcome measure.

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=229 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities- Hematology	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) up to End of treatment visit (within 7 days of treatment) [approximately maximum up to 7 weeks]

Population: Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo). Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Laboratory test abnormalities in serum chemistry included: alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, Bilirubin (total), calcium (high, low), cholesterol (total), creatine kinase, creatinine, estimated glomerular filtration rate (eGFR), Modification of Diet in Renal Disease (MDRD), glucose, (high, low), lactate dehydrogenase low density lipoprotein (LDL) cholesterol (fasting, non-fasting), potassium (high, low), sodium (high, low), triglycerides (fasting, non-fasting), uric acid. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Number of participants who had serum chemistry parameter abnormality Grade 3 to 4 are reported in this outcome measure. Number of participants with non-zero laboratory abnormalities are reported in this outcome measure.

Outcome measures

Measure	Rimegepant 25 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=229 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities- Serum Chemistry Creatine kinase	2 Participants	0 Participants	0 Participants
Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities- Serum Chemistry Triglycerides	1 Participants	0 Participants	1 Participants
Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities- Serum Chemistry LDL cholesterol	4 Participants	3 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) up to End of treatment visit (within 7 days of treatment) [approximately maximum up to 7 weeks]

Population: Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo). Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure.

Laboratory test abnormalities in urinalysis included: Urine glucose, Urine protein, pH, specific gravity, ketones, nitrites, urobilinogen, leukocyte esterase, blood. If blood, protein or leukocytes are positive and determined clinically significant by the investigator, then the participants were returned for an unscheduled visit for microscopic examination. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Number of participants who had urinalysis parameter abnormality Grade 3 to 4 are reported in this outcome measure. Number of participants with non-zero laboratory abnormalities are reported in this outcome measure.

Outcome measures

Measure	Rimegepant 25 mg n=236 Participants Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 Participants Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=228 Participants Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities- Urinalysis	0 Participants	0 Participants	1 Participants

Adverse Events

Rimegepant 25 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Rimegepant 75 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rimegepant 25 mg n=239 participants at risk Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 participants at risk Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=229 participants at risk Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Psychiatric disorders Suicidal ideation	0.00% 0/239 • From the day of signing informed consent up to end of treatment visit (approximately maximum up to 11 weeks) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo).	0.42% 1/238 • From the day of signing informed consent up to end of treatment visit (approximately maximum up to 11 weeks) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo).	0.00% 0/229 • From the day of signing informed consent up to end of treatment visit (approximately maximum up to 11 weeks) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo).

Other adverse events

Measure	Rimegepant 25 mg n=239 participants at risk Participants were randomized to receive ODT of rimegepant 25 mg and of placebo (matched to rimegepant 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Rimegepant 75 mg n=238 participants at risk Participants were randomized to receive ODT of rimegepant 75 mg and of placebo (matched to rimegepant 25 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.	Placebo n=229 participants at risk Participants were randomized to receive ODT of placebo (each matched to rimegepant 25 and 75 mg) sublingually when they experienced a migraine headache of moderate to severe intensity, within 45 days of randomization on Day 1.
Infections and infestations Nasopharyngitis	1.3% 3/239 • From the day of signing informed consent up to end of treatment visit (approximately maximum up to 11 weeks) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo).	1.3% 3/238 • From the day of signing informed consent up to end of treatment visit (approximately maximum up to 11 weeks) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo).	0.87% 2/229 • From the day of signing informed consent up to end of treatment visit (approximately maximum up to 11 weeks) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set consisted of participants in the enrolled analysis set who took the study drug (rimegepant 25 mg, rimegepant 75 mg, or placebo).

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publication until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER