Efficacy and Safety Trial of Rimegepant for Migraine Prevention in Adults

A migraine day: any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache: a migraine with or without aura, lasting for ≥30 minutes, and meeting at least 1 of the following criteria (a and/or b): a) ≥2 of the following: unilateral location, pulsating quality, moderate to severe pain intensity, aggravation by or causing avoidance of routine physical activity; b) ≥1 of the following: nausea and/or vomiting, photophobia, and phonophobia. If the participant took a migraine-specific medication during aura or to treat headache on a calendar day, it was counted as a migraine day regardless of the duration and pain features/associated symptoms. Months were defined as 28-day intervals. The change from baseline was calculated as the number of monthly migraine days during the last 4 weeks of the DBT phase (Weeks 9 to 12) minus number of monthly migraine days during the OP.

Time frame: OP and Weeks 9 to 12 of the DBT phase

Population: The analysis was performed on evaluable modified intent to treat (mITT) participants. Evaluable participants are those with ≥ 14 days of electronic diary efficacy data (not necessarily consecutive) in both the OP and ≥ 1 month (4-week interval) in the DBT phase.

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (as previously described). If the participant took a migraine-specific medication during aura or to treat headache on a calendar day, it was counted as a migraine day regardless of the duration and pain features/associated symptoms. Months were defined as 28-day intervals. The change from baseline was calculated as the number of monthly migraine days during the DBT phase (Weeks 1 to 12) minus the number of monthly migraine days during the OP.

Time frame: OP and Weeks 1 to 12 of the DBT phase

Population: The analysis was performed on evaluable mITT participants.

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (as previously described). If the participant took a migraine-specific medication during aura or to treat headache on a calendar day, it was counted as a migraine day regardless of the duration and pain features/associated symptoms. Months were defined as 28-day intervals. The change from baseline was calculated as the number of monthly migraine days during the first 4 weeks of the DBT phase (Weeks 1 to 4) minus the number of monthly migraine days during the OP.

Time frame: OP and Weeks 1 to 4 of the DBT phase

Population: The analysis was performed on evaluable mITT participants.

A rescue medication day was a day on which the participant took triptan, ergotamine, or other permitted medication to acutely treat headache or aura. Months were defined as 28-day intervals.

Time frame: Weeks 9 to 12 of the DBT phase

Population: The analysis was performed on evaluable mITT participants

The Migraine Disability Assessment (MIDAS) is a retrospective, self-administered, 5-item questionnaire that measures headache-related disability as lost time due to headache from paid work or school, household work, and non-work activities. Participants provide the number of missed work or school days; missed household chores days; missed social or leisure activity days; and days at work or school, and separately at home, where productivity was reduced by half or more in the last 3 months (scale: 0 - 90 for each of 5 subscales). The 5 subscale scores are summed to compute the MIDAS total score (scale: 0 - 450). Lower scores indicate less headache-related disability. The change from baseline was calculated as the MIDAS total score at Week 12 of the DBT phase minus the MIDAS total score at baseline.

Time frame: Baseline, Week 12 of the DBT Phase

Population: The analysis was performed on evaluable mITT participants

The Migraine Specific Quality of Life (MSQoL) is a self-administered, 14-item instrument that has been validated in 3 domains: role restriction, role prevention, and the emotional function. The role function-restrictive domain consists of 7 items that describe how migraine limits one's daily social and work-related activities. Participants respond to items using a 6-point scale: none of the time, a little bit of the time, some of the time, a good bit of the time, most of the time, and all of the time, which are assigned scores of 1 to 6, respectively. Item scores are recoded using (7 - original score). Next, raw dimension scores are computed as a sum of recoded item scores and rescaled from a 0 to 100 scale such that higher scores indicate better quality of life. The change from baseline was calculated as the MSQoL restrictive role function domain score at Week 12 of the DBT phase minus the MSQoL restrictive role function domain score at baseline.

Time frame: Baseline, Week 12 of the DBT Phase

Population: The analysis was performed on evaluable mITT participants.

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (as previously described). If the participant took a migraine-specific medication during aura or to treat headache on a calendar day, it was counted as a migraine day regardless of the duration and pain features/associated symptoms. A moderate or severe migraine day was a migraine day of moderate or severe pain intensity. Months were defined as 28-day intervals. A reduction of at least 50% in the mean number of moderate or severe monthly migraine days was determined if the number of moderate or severe monthly migraine days in the last 4 weeks of the DBT (Weeks 9 to 12) was less than or equal to half (50%) of the number of moderate or severe monthly migraine days in the OP.

Time frame: OP and Weeks 9 to 12 of the DBT phase

Population: The analysis was performed on evaluable mITT participants.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition on-treatment in a patient or clinical investigation participant administered an investigational (medicinal) product and that did not necessarily have a causal relationship with this treatment. An SAE was defined as any event that met any of the following criteria: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received rimegepant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention.

Time frame: Weeks 1 to 12 of the DBT phase

Population: The analysis was performed on the participants treated in the DBT phase.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition on-treatment in a patient or clinical investigation participant administered an investigational (medicinal) product and that did not necessarily have a causal relationship with this treatment. An SAE was defined as any event that met any of the following criteria: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received rimegepant; other important medical events that may not have resulted in death, be life-threatening, or required hospitalization, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention.

Time frame: OLE Phase (Weeks 13 through 64)

Population: Open-Label (OL) rimegepant treated participants included enrolled participants who received at least one dose of OL rimegepant (non-missing OL rimegepant start date).

Clinically significant laboratory abnormalities were defined as Grade 3 to 4 laboratory test results according to numeric laboratory test criteria found in Common Technical Criteria for Adverse Events (CTCAE) Version 5.0 (2017) if available; otherwise, according to Division of Acquired Immune Deficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017) for glucose, LDL-cholesterol, uric acid, and urinalysis. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis. Participants must have had a non-missing measurement in the DBT phase to be included for a given parameter.

Time frame: Weeks 1 to 12 of the DBT phase

Population: The analysis was performed on the participants treated in the DBT phase.

Clinically significant laboratory abnormalities were defined as Grade 3 to 4 laboratory test results according to numeric laboratory test criteria found in CTCAE Version 5.0 (2017) if available; otherwise, according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017) for glucose, LDL-cholesterol, uric acid, and urinalysis. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis. Participants must have had a non-missing measurement in the OLE phase to be included for a given parameter.

Time frame: OLE Phase (Weeks 13 through 64)

Population: OL rimegepant treated participants with available data were included in the analysis.

Elevations of AST or ALT \> 3 x ULN concurrent with TBL \> 2 x ULN were defined as elevations on the same collection date. Participants must have had a non-missing AST, ALT, or TBL measurement in the OLE phase to be included.

Time frame: Weeks 1 to 12 of the DBT phase

Population: The analysis was performed on the participants treated in the DBT phase.

Hepatic AEs were defined as all preferred terms in the DBT phase under the Hepatic Disorders Standardized Medical Dictionary (Version 21.1) for Regulatory Activities Query (SMQ), except those preferred terms in the Congenital, Familial, Neonatal and Genetic Disorders of the Liver SMQ.

Time frame: Weeks 1 to 12 of the DBT phase

Population: The analysis was performed on the participants treated in the DBT phase.

Hepatic AEs were defined as all preferred terms in the OLE phase under the Hepatic Disorders SMQ, except those preferred terms in the Congenital, Familial, Neonatal and Genetic Disorders of the Liver SMQ.

Time frame: OLE Phase (Weeks 13 through 64)

Population: OL rimegepant treated participants were included in the analysis.

Elevations of AST or ALT \> 3 x ULN concurrent with TBL \> 2 x ULN were defined as elevations on the same collection date. Participants must have had a non-missing AST, ALT, or TBL measurement in the DBT phase to be included.

Time frame: OLE Phase (Weeks 13 through 64)

Population: OL rimegepant treated participants with available data were included in the analysis.