Efficacy and Safety Study of Rimegepant for Migraine Prevention in Japanese Subjects (Japan Only)

Migraine day: 1) day of electronic diary (eDiary) efficacy data with a qualified migraine headache, defined as: Headache lasted for >= 30 minutes and had 2 or more of following pain features: Unilateral and pulsating, moderate or severe pain intensity, worsen or avoid physical activity with one or more of the following associated symptoms: nausea, vomiting, both photophobia and phonophobia or 2) Acute migraine-specific medication day as eDiary efficacy data with a "yes" response to either of the 2 questions about taking triptan or ergotamine to treat headache or non-scheduled OL Rimegepant dosing day. The number of migraine days per month were prorated to 28 days and derived for month (i.e., 4-week interval) in on-DBT efficacy analysis period as follows: 28*(total number of migraine days in month [Week 9 to 12])/ (total number of efficacy data days in month [Week 9 to 12]).

Percentage of participants with >= 50% reduction, from baseline in mean number of pain intensity (moderate or severe) in each month of DBT phase are included in this outcome measure. Migraine days per month are assessed as "migraine days per 4 weeks" to correspond with the 4-week visit schedule. Migraine days per month are based on 4-week intervals and are prorated to account for missing migraine reports. The number of migraine days per month were prorated to 28 days and derived for month (i.e., 4-week interval) in on-DBT efficacy analysis period as follows: 28*(total number of migraine days in month [Week 9 to 12])/ (total number of efficacy data days in month [Week 9 to 12])

Migraine day:1) day of eDiary efficacy data with a qualified migraine headache, defined as: Headache lasted for >= 30 minutes and had 2 or more of following pain features: Unilateral and pulsating, moderate or severe pain intensity, worsen or avoid physical activity with one or more following associated symptoms: nausea, vomiting, both photophobia and phonophobia or 2) Acute migraine-specific medication day as eDiary efficacy data with a "yes" response to either of the 2 questions about taking triptan or ergotamine to treat headache or non-scheduled OL Rimegepant dosing day. In the model analysis, this outcome was also evaluated based on the monthly number of migraine days (and estimated the migraine days per month over the entire DBT phase). The number of migraine days per month were prorated to 28 days and derived for month (i.e.,4-week interval) in on-DBT efficacy analysis period as follows: 28*(total number of migraine days in month/ (total number of efficacy data days in month).

Migraine day: 1) day of eDiary efficacy data with a qualified migraine headache, defined as: Headache lasted for >= 30 minutes and had 2 or more of following pain features: Unilateral and pulsating, moderate or severe pain intensity, worsen or avoid physical activity with one or more of the following associated symptoms: nausea, vomiting, both photophobia and phonophobia or 2) Acute migraine-specific medication day as eDiary efficacy data with a "yes" response to either of the 2 questions about taking triptan or ergotamine to treat headache or non-scheduled OL Rimegepant dosing day. The number of migraine days per month were prorated to 28 days and derived for month (i.e., 4-week interval) in on-DBT efficacy analysis period as follows: 28*(total number of migraine days in month [Week 1 to 4])/ (total number of efficacy data days in month [Week 1 to 4]).

An acute migraine-specific medication day was defined as day of eDiary efficacy data with a "yes" response to either of the 2 questions about taking triptan or ergotamine to treat headache or aura. Migraine days per month are assessed as "migraine days per 4 weeks" to correspond with the 4-week visit schedule. Migraine days per month are based on 4-week intervals and are prorated to account for missing migraine reports. The number of acute migraine-specific medication days per month was prorated to 28 days and derived for month (i.e., 4-week interval) in the on-DBT efficacy analysis period: 28*(total number of acute migraine-specific medication days in the month [Week 9 to 12])/ (total number of efficacy data days in the month [Week 9 to 12]).

MSQoL is a self-administered, 14-item instrument 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.

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.

EQ-5D-5L is a standardized measure of health status. The EQ-5D-5L consisted of EQ-5D-5L descriptive system and the EQ VAS. For EQ VAS participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.

An Adverse Event (AE) was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Definition of AE in terms of intensity: Mild: Is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate: Is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the participant. Severe: Interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.

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

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. 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.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. A 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 offspring who received rimegepant were considered an important medical event.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. In this outcome measure participants with adverse events leading to discontinuation of study drug were reported.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. In this outcome measure participants with adverse events leading to discontinuation of study drug were reported.

The laboratory parameters were graded according to the National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version (v)5.0 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE and Grade 4=life-threatening consequences; urgent intervention indicated. Hematology parameters included: eosinophils, hemoglobin (high, low), lymphocytes (high, low), white blood cell count (WBC) (low, high), platelets, and neutrophils. hematocrit, red blood cell count, Number of participants with non-zero laboratory abnormalities of hematology parameters were reported in this outcome measure.

The laboratory parameters were graded according to the NCI CTCAE v5.0 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE and Grade 4=life-threatening consequences; urgent intervention indicated. Hematology parameters included: eosinophils, hemoglobin (high, low), lymphocytes (high, low), WBC (low, high), platelets, and neutrophils. Number of participants with non-zero laboratory abnormalities of hematology parameters were reported in this outcome measure.

The laboratory parameters were graded according to the NCI CTCAE v5.0 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Serum chemistry parameters included: creatine kinase, low density lipoprotein (LDL) cholesterol, LDL cholesterol, fasting, triglycerides, triglycerides, fasting and not fasting, alanine aminotransferase increased, albumin, alkaline phosphatase, aspartate aminotransferase increased, bicarbonate, bilirubin, calcium (high, low), cholesterol, creatinine, estimated glomerular filtration rate (eGFR), glucose (high, low), lactate dehydrogenase, LDL cholesterol, potassium (high, low), sodium (high, low), and uric acid. Number of participants with non-zero laboratory abnormalities of serum chemistry parameters were reported in this outcome measure.

The laboratory parameters were graded according to the NCI CTCAE v5.0 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Serum chemistry parameters included: creatine kinase, LDL cholesterol, LDL cholesterol, triglycerides, triglycerides, alanine aminotransferase increased, albumin, alkaline phosphatase, aspartate aminotransferase increased, bicarbonate, bilirubin, calcium (high, low), cholesterol, creatinine, eGFR, glucose (high, low), lactate dehydrogenase, potassium (high, low), sodium (high, low), uric acid. Number of participants with non-zero laboratory abnormalities of serum chemistry parameters were reported in this outcome measure.

The laboratory parameters were graded according to the NCI CTCAE v5.0 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE and Grade 4=life-threatening consequences; urgent intervention indicated. Urinalysis parameters included: urine glucose and urine protein.

The laboratory parameters were graded according to the NCI CTCAE v5.0 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE and Grade 4=life-threatening consequences; urgent intervention indicated. Urinalysis parameters included: urine glucose and urine protein. Number of participants with non-zero laboratory abnormalities of urinalysis parameters were reported in this outcome measure.

Number of participants with ALT or AST >3*ULN concurrent with TBIL >2*ULN in DBT phase were reported in this outcome measure.

Number of participants with ALT or AST >3*ULN concurrent with TBIL >2*ULN in OLE phase were reported in this outcome measure.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Hepatic AEs included cirrhosis, hepatic failure, hepatitis, jaundice, or liver failure.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Hepatic AEs included cirrhosis, hepatic failure, hepatitis, jaundice, or liver failure.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Hepatic AEs included cirrhosis, hepatic failure, hepatitis, jaundice, or liver failure. Number of participants with Hepatic-related AEs leading to study drug discontinuation were reported in this outcome measure.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. Hepatic AEs included cirrhosis, hepatic failure, hepatitis, jaundice, or liver failure. Number of participants with Hepatic-related AEs leading to study drug discontinuation were reported in this outcome measure.