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

Phase 3

Completed

Conditions: Migraine

Interventions: Drug: Placebo
Drug: Rimegepant

Registration Number: NCT05399485

Lead Sponsor: Pfizer

Brief Summary: This study is being conducted to evaluate the efficacy, safety, and tolerability of rimegepant in Japanese subjects for the prevention of migraine.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 496

Inclusion Criteria

Subject has at least 1 year history of migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following:

Age of onset of migraines prior to 50 years of age.
Migraine attacks, on average, lasting 4 to 72 hours if untreated.
Per subject report, 4 to18 migraine attacks of moderate or severe intensity per month within the last 3 months prior to the Screening Visit (month is defined as 4 weeks for the purpose of this protocol).
4 or more migraine days during Observation Period.
Not more than 18 headache days during the Observation Period.
Ability to distinguish migraine attacks from tension/cluster headaches.
Subjects on prophylactic migraine medication are permitted to remain on therapy if the dose has been stable for at least 3 months (12 weeks) prior to the Observation Period, and the dose is not expected to change during the course of the study.
Subjects with contraindications for use of triptans may be included provided they meet all other study entry criteria.

Exclusion Criteria

Subject has a history of migraine with brainstem aura (basilar migraine), hemiplegic migraine or retinal migraine.
Subjects with headaches occurring 19 or more days per month (migraine or non-migraine) in any of the 3 months prior to the Screening Visit.
History of systemic use of analgesics (e.g. nonsteroidal anti-inflammatory drugs [NSAIDs] or acetaminophen) on ≥ 15 days per month during the 3 months (12 weeks) prior to the Screening Visit.
Subject with a history of HIV disease.
Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS),Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening.
Uncontrolled hypertension, or uncontrolled diabetes (however subjects can be included who have stable hypertension and/or diabetes for 3 months prior to screening).
Subject with other pain syndromes, psychiatric conditions, dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments.
Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease that causes malabsorption.
The subject has a history or current evidence of any unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known or suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial.
History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or subjects who have met DSM-V criteria for any significant substance use disorder within the past 12 months from the date of the screening visit.
Participation in any other investigational clinical trial while participating in this clinical trial.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Randomization Phase: one matching placebo every other day until week 12
Rimegepant	Rimegepant	Randomization Phase: one 75 mg rimegepant (BHV3000) oral disintegration tablet every other day until Week 12

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Number of Migraine Days Per Month From Week 9 to 12 of the Double-Blind Treatment (DBT) Phase	Baseline, Week 9 to Week 12 of the DBT phase	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 \[Week 9 to 12\]).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With at Least 50% Reduction From Baseline in the Mean Number of Moderate to Severe Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of the DBT Phase	Baseline, Week 9 to Week 12 of the DBT phase	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 \[Week 9 to 12\])
Mean Change From Baseline in Number of Migraine Days Per Month Over the Entire DBT Phase (Weeks 1 to 12)	Baseline, Week 1 to Week 12 of the DBT phase	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).
Mean Change From Baseline in Number of Migraine Days Per Month From Week 1 to 4 of the DBT Phase	Baseline, Week 1 to Week 4 of the DBT phase	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 \[Week 1 to 4\]).
Mean Number of Acute Migraine-specific Medication Days Per Month From Week 9 to 12 of the DBT Phase	Week 9 to Week 12 of the DBT phase	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 \[Week 9 to 12\]).
Mean Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire (MSQoL) v 2.1 Role Function - Restrictive Domain Score at Week 12 of the DBT Phase	Baseline, Week 12 of the DBT phase	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.
Mean Change From Baseline in the Migraine Disability Assessment Total Score (MIDAS) at Week 12 of the DBT Phase	Baseline, Week 12 of the DBT phase	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.
Mean Change From Baseline in the EuroQol 5 Dimensions 5-level (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Week 12 of the DBT Phase	Baseline, Week 12 of the DBT phase	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.
Number of Participants With Adverse Events (AEs) By Intensity in DBT Phase	From Day 1 of dosing up to 7 days post last dose of study drug in DBT phase or prior to start of OL rimegepant dose, whichever was earlier (maximum up to 13 weeks)	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.
Number of Participants With AEs By Intensity in Open-Label Extension (OLE) Phase	From Day 1 of OL Rimegepant dosing up to 7 days post last dose (maximum up to 41 weeks)	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.
Number of Participants With Serious Adverse Events (SAEs) in DBT Phase	From Day 1 of dosing up to 7 days post last dose of study drug in DBT phase or prior to start of OL rimegepant dose, whichever was earlier (maximum up to 13 weeks)	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.
Number of Participants With SAEs in OLE Phase	From Day 1 of OL Rimegepant dosing up to 7 days post last dose (maximum up to 41 weeks)	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.
Number of Participants With AEs Leading to Discontinuation of Study Drug in DBT Phase	From Day 1 of dosing up to 7 days post last dose of study drug in DBT phase or prior to start of OL rimegepant dose, whichever was earlier (maximum up to 13 weeks)	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.
Number of Participants With AEs Leading to Discontinuation of Study Drug in OLE Phase	From Day 1 of OL Rimegepant dosing up to 7 days post last dose (maximum up to 41 weeks)	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 will be reported.
Number of Participants With Grade 3 to 4 Laboratory Abnormalities in DBT Phase: Hematology Parameters	From Day 1 of dosing up to 7 days post last dose of study drug in DBT phase or prior to start of OL rimegepant dose, whichever was earlier (maximum up to 13 weeks)	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. 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.
Number of Participants With Grade 3 to 4 Laboratory Abnormalities in OLE Phase: Hematology Parameters	From Day 1 of OL Rimegepant dosing up to 7 days post last dose (maximum up to 41 weeks)	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. Hematology parameters included: Eosinophils, hemoglobin (high, low), lymphocytes (high, low), WBC (low, high), platelets, and neutrophils. hematocrit, red blood cell count, Number of participants with non-zero laboratory abnormalities of hematology parameters will be reported in this outcome measure.
Number of Participants With Grade 3 to 4 Laboratory Abnormalities in DBT Phase: Serum Chemistry Parameters	From Day 1 of dosing up to 7 days post last dose of study drug in DBT phase or prior to start of OL rimegepant dose, whichever was earlier (maximum up to 13 weeks)	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, fasting, Triglycerides, Triglycerides, fasting, Alanine aminotransferase increased, Albumin, Alkaline phosphatase, Aspartate aminotransferase increased, Bicarbonate, Bilirubin, Calcium (high, low), Cholesterol, Creatinine, eGFR, Glucose (high, low), Lactate dehydrogenase, LDL cholesterol, not fasting, 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.
Number of Participants With Grade 3 to 4 Laboratory Abnormalities in OLE Phase: Serum Chemistry Parameters	From Day 1 of OL Rimegepant dosing up to 7 days post last dose (maximum up to 41 weeks)	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, fasting, Triglycerides, Triglycerides, fasting, Alanine aminotransferase increased, Albumin, Alkaline phosphatase, Aspartate aminotransferase increased, Bicarbonate, Bilirubin, Calcium (high, low), Cholesterol, Creatinine, eGFR, Glucose (high, low), Lactate dehydrogenase, LDL cholesterol, not fasting, Potassium (high, low), Sodium (high, low), Uric acid. Number of participants with non-zero laboratory abnormalities of serum chemistry parameters will be reported in this outcome measure.
Number of Participants With Grade 3 to 4 Changes in DBT Phase: Urinalysis	From Day 1 of dosing up to 7 days post last dose of study drug in DBT phase or prior to start of OL rimegepant dose, whichever was earlier (maximum up to 13 weeks)	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. Urinalysis parameters included: Urine glucose and Urine protein.
Number of Participants With Grade 3 to 4 Changes in OLE Phase: Urinalysis	From Day 1 of OL Rimegepant dosing up to 7 days post last dose (maximum up to 41 weeks)	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. Urinalysis parameters included: Urine glucose and Urine protein.
Number of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >3* Upper Lower Limit of Normal (ULN) Concurrent With Total Bilirubin (TBIL) >2*ULN in DBT Phase	From Day 1 of dosing up to 7 days post last dose of study drug in DBT phase or prior to start of OL rimegepant dose, whichever was earlier (maximum up to 13 weeks)	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	From Day 1 of OL Rimegepant dosing up to 7 days post last dose (maximum up to 41 weeks)	Number of participants with ALT or AST \>3\ULN concurrent with TBIL \>2\ULN in OLE phase will be reported in this outcome measure.
Number of Participants With Hepatic-related AEs in the DBT Phase	From Day 1 of dosing up to 7 days post last dose of study drug in DBT phase or prior to start of OL rimegepant dose, whichever was earlier (maximum up to 13 weeks)	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 in the OLE Phase	From Day 1 of OL Rimegepant dosing up to 7 days post last dose (maximum up to 41 weeks)	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 in the DBT Phase	From Day 1 of dosing up to 7 days post last dose of study drug in DBT phase or prior to start of OL rimegepant dose, whichever was earlier (maximum up to 13 weeks)	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.
Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation in the OLE Phase	From Day 1 of OL Rimegepant dosing up to 7 days post last dose (maximum up to 41 weeks)	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 will be reported in this outcome measure.

Trial Locations

Locations (44): Medical Corporation Seikokai Takanoko Hospital
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Matsuyama-shi, Ehime, Japan
Jinnouchi Neurosurgical Clinic
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Kasuga-shi, Fukuoka, Japan
Ikeda Neurosurgical Clinic
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Kasuga-shi, Fukuoka, Japan
SUBARU Health Insurance Society Ota Memorial Hospital
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Ota-shi, Gunma, Japan
Doi Clinic Internal Medicine/Neurology
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Hiroshima-shi, Hiroshima, Japan
Japanese Red Cross Asahikawa Hospital
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Asahikawa-shi, Hokkaido, Japan
Nakamura Memorial Hospital
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Chuo-ku, Hokkaido, Japan
Higashi Sapporo Neurology and Neurosurgery Clinic
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Sapporo-shi, Hokkaido, Japan
Konan Medical Center
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Higashinada-ku, Hyōgo, Japan
Nishinomiya Munic. Ctr. Hosp.
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Nishinomiya-shi, Hyōgo, Japan
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Medical Corporation Seikokai Takanoko Hospital
🇯🇵Matsuyama-shi, Ehime, Japan