Efficacy and Safety Study of Rimegepant for the Acute Treatment of Migraine in Japanese Subjects (Japan Only)

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).

Time frame: 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.

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.

Time frame: 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).

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

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.

Time frame: 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).

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

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.

Time frame: 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 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.

Time frame: 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.

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.

Time frame: 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 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.

Time frame: 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 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.

Time frame: 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 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.

Time frame: 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.