Brief Summary
The purpose of this study is to compare the efficacy and safety of daily and every other day dosing of rimegepant to placebo as a preventive treatment for episodic migraine.
Brief Title
Efficacy and Safety Study of Rimegepant in Episodic Migraine Prevention With Multiple Dosing Regimens
Categories
Completion Date
Completion Date Type
Actual
Conditions
Migraine
Eligibility Criteria
Inclusion Criteria:
1\) Target Population: Subject has at least 1 year history of episodic migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following:
1. Age of onset of migraines prior to 50 years of age
2. Migraine attacks, on average, lasting 4-72 hours if untreated
3. Per subject report, 4-14 migraine attacks per month within the last 3 months prior to the Screening Visit (month is defined as 4 weeks for the purpose of this protocol
Exclusion Criteria:
1. Sex and Reproductive Status:
1. WOCBP who are unwilling or unable to use an acceptable contraceptive method or abstinence to avoid pregnancy for the entire study and for 60 days after the last dose of study drug
2. Women who are pregnant or breastfeeding
3. Women with a positive pregnancy test at screening or prior to study drug administration
2. Prohibited Medications:
1. Use of prophylactic migraine medication within 30 days prior to the Screening Visit.
2. History of use of analgesics (e.g., non-steroidal anti-inflammatory drugs \[NSAIDs\] or acetaminophen) on ≥ 15 days per month during the 3 months (12 weeks) prior to the Screening Visit.
3. Use of medication accepted for treatment of acute migraine for a nonmigraine indication on ≥ 15 days per month during the 3 months (12 weeks) prior to the Screening Visit.
4. Subjects who previously discontinued biologic migraine medication must have done so at least 6 months (24 weeks) prior to the Screening Visit.
5. Subjects taking a prohibited medication as defined per protocol
1\) Target Population: Subject has at least 1 year history of episodic migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following:
1. Age of onset of migraines prior to 50 years of age
2. Migraine attacks, on average, lasting 4-72 hours if untreated
3. Per subject report, 4-14 migraine attacks per month within the last 3 months prior to the Screening Visit (month is defined as 4 weeks for the purpose of this protocol
Exclusion Criteria:
1. Sex and Reproductive Status:
1. WOCBP who are unwilling or unable to use an acceptable contraceptive method or abstinence to avoid pregnancy for the entire study and for 60 days after the last dose of study drug
2. Women who are pregnant or breastfeeding
3. Women with a positive pregnancy test at screening or prior to study drug administration
2. Prohibited Medications:
1. Use of prophylactic migraine medication within 30 days prior to the Screening Visit.
2. History of use of analgesics (e.g., non-steroidal anti-inflammatory drugs \[NSAIDs\] or acetaminophen) on ≥ 15 days per month during the 3 months (12 weeks) prior to the Screening Visit.
3. Use of medication accepted for treatment of acute migraine for a nonmigraine indication on ≥ 15 days per month during the 3 months (12 weeks) prior to the Screening Visit.
4. Subjects who previously discontinued biologic migraine medication must have done so at least 6 months (24 weeks) prior to the Screening Visit.
5. Subjects taking a prohibited medication as defined per protocol
Inclusion Criteria
Inclusion Criteria:
1\) Target Population: Subject has at least 1 year history of episodic migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following:
1. Age of onset of migraines prior to 50 years of age
2. Migraine attacks, on average, lasting 4-72 hours if untreated
3. Per subject report, 4-14 migraine attacks per month within the last 3 months prior to the Screening Visit (month is defined as 4 weeks for the purpose of this protocol
1\) Target Population: Subject has at least 1 year history of episodic migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following:
1. Age of onset of migraines prior to 50 years of age
2. Migraine attacks, on average, lasting 4-72 hours if untreated
3. Per subject report, 4-14 migraine attacks per month within the last 3 months prior to the Screening Visit (month is defined as 4 weeks for the purpose of this protocol
Gender
All
Gender Based
false
Keywords
Migraine
Episodic Migraine
Adult Migraine
Calcitonin Gene-related Peptide
Migraine Prevention
Migraine Prophylaxis
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05217927
Org Class
Industry
Org Full Name
Pfizer
Org Study Id
BHV3000-404
Overall Status
Completed
Phases
Phase 4
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 4 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rimegepant in Episodic Migraine Prevention With Multiple Dosing Regimens
Primary Outcomes
Outcome Description
A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, and meeting either \>=2 of the pain features: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity OR \>=1 of the associated symptoms: nausea and/or vomiting; photophobia and phonophobia. The number of migraine days per month were prorated to 28 days and derived for a month in on-DBT efficacy analysis period as follows: 28\*(total number of migraine days through Month 3 \[Weeks 1 to 12\]/ (total number of e-diary efficacy data days through Month 3 \[Weeks 1 to 12\]). Mean change in number of migraine days per month in DBT phase as compared to OP phase was calculated and reported in this outcome measure.
Outcome Measure
Mean Change From Observation Phase (OP) in the Number of Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12)
Outcome Time Frame
Observation phase (from 31 days prior to randomization), DBT phase (through Month 3 [Week 1 to 12])
Secondary Ids
Secondary Id
2021-005239-22
Secondary Id
C4951010
Secondary Outcomes
Outcome Description
Percentage of participants with \>= 50% reduction from OP, in number of migraine days (moderate or severe) in the overall DBT phase is reported in this outcome measure. The number of migraine days per month were prorated to 28 days and derived for a month in on-DBT efficacy analysis period as follows: 28\*(total number of migraine days through Month 3 \[Weeks 1 to 12\]/ (total number of e-diary efficacy data days through Month 3 \[Weeks 1 to 12\]).
Outcome Time Frame
DBT phase (through Month 3 [Week 1 to 12])
Outcome Measure
Percentage of Participants With Greater Than Equal to (>=) 50 Percent (%) Reduction From OP in Number of Moderate to Severe Migraine Days Per Month Over the Entire DBT Phase (Weeks 1 to 12)
Outcome Description
A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, and meeting either \>=2 of the pain features: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity OR \>=1 of the associated symptoms: nausea and/or vomiting; photophobia and phonophobia. The number of migraine days per month were prorated to 28 days and derived a month (i.e., 4-week interval) in on-DBT efficacy analysis period as follows: 28\*(total number of migraine days in the month) / (total number of e-diary efficacy data in the month). Mean change in number of migraine days per month in the last 4 weeks of DBT phase as compared to OP phase was calculated and reported in this outcome measure.
Outcome Time Frame
Observation phase (from 31 days before randomization), Week 9 to Week 12 of the DBT phase
Outcome Measure
Mean Change From OP in the Number of Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of DBT Phase
Outcome Description
A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, and meeting either \>=2 of the pain features: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity OR \>=1 of the associated symptoms: nausea and/or vomiting; photophobia and phonophobia. The number of migraine days per month were prorated to 28 days and derived a month (i.e., 4-week interval) in on-DBT efficacy analysis period as follows: 28\*(total number of migraine days in the month / (total number of e-diary efficacy data in the month. Mean change in number of migraine days per month in the first 4 weeks of DBT phase as compared to OP phase was calculated and reported in this outcome measure.
Outcome Time Frame
Observation phase (from 31 days before randomization), Week 1 to Week 4 of the DBT phase
Outcome Measure
Mean Change From OP in the Number of Migraine Days Per Month in the First 4 Weeks (Weeks 1 to 4) of DBT Phase
Outcome Description
An acute migraine-specific medication day was defined as any calendar day during which the participant took a migraine-specific medication (i.e., triptan or ergotamine). The number of acute migraine-specific medication days per month were prorated to 28 days and derived for on-DBT efficacy analysis period as follows: 28\*(total number of acute migraine-specific medication days through Month 3/ (total number of e-Diary efficacy data days through Month 3).
Outcome Time Frame
DBT phase (through Month 3 [Week 1 to 12])
Outcome Measure
Mean Number of Acute Migraine-Specific Medication Days Per Month Over the Entire DBT Phase (Weeks 1 to 12)
Outcome Description
MSQoL is a self-administered, 14-item instrument validated in 3 domains: role restriction, role prevention, and the emotional function. The restrictive role function domain consisted of 7 items that described how migraine limited one's daily social and work-related activities. Participants were required to respond to items using a 6-point scale ranging from 1 to 6, where "1: none of the time," "2: a little bit of the time," "3: some of the time," "4: a good bit of the time," "5: most of the time," and "6: all of the time,". Item scores were recoded using (7 - original score). Raw dimension scores for restrictive role function domain were computed as a sum of recoded item scores and rescaled from a 0 to 100 scale such that lower score (0) indicated poor quality of life and higher scores (100) indicated better quality of life.
Outcome Time Frame
Baseline (Day 1), Week 12 of the DBT phase
Outcome Measure
Mean Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire (MSQoL) Version 2.1 Restrictive Role Function Domain Score at Week 12 of the DBT Phase
Outcome Description
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 did not necessarily have a causal relationship with this treatment. AEs were categorized as mild: usually transient and required only minimal treatment or therapeutic intervention. The event did not generally interfere with usual activities of daily living. Moderate: was usually alleviated with additional specific therapeutic intervention. The event interfered with usual activities of daily living, causing discomfort but posed no significant or permanent risk of harm to the participant. Severe: Interrupted usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. AEs included both non-SAEs and serious adverse events (SAEs).
Outcome Time Frame
DBT: From Week 1 to Week 20
Outcome Measure
Number of Participants With Mild, Moderate and Severe Adverse Events (AEs) in DBT Phase
Outcome Description
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 did not necessarily have a causal relationship with this treatment. AEs were categorized as mild: usually transient and required only minimal treatment or therapeutic intervention. The event did not generally interfere with usual activities of daily living. Moderate: was usually alleviated with additional specific therapeutic intervention. The event interfered with usual activities of daily living, causing discomfort but posed no significant or permanent risk of harm to the participant. Severe: Interrupted usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. AEs included both non-SAEs and SAEs.
Outcome Time Frame
OLE: From Week 12 to Week 32
Outcome Measure
Number of Participants With Mild, Moderate and Severe AEs OLE Phase
Outcome Description
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 did not necessarily have a causal relationship with this treatment. An SAE was any event that met any of the following criteria at any dose: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of the participant who received rimegepant and other important medical events.
Outcome Time Frame
DBT: From Week 1 to Week 20
Outcome Measure
Number of Participants With Serious Adverse Events (SAEs) in DBT Phase
Outcome Description
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 did not necessarily have a causal relationship with this treatment. An SAE was any event that met any of the following criteria at any dose: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of the participant who received rimegepant and other important medical events.
Outcome Time Frame
OLE: From Week 12 to Week 32
Outcome Measure
Number of Participants With SAEs in OLE Phase
Outcome Description
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 did not necessarily have a causal relationship with this treatment. In this outcome measure, participants with adverse events leading to study drug discontinuation were reported.
Outcome Time Frame
DBT: From Week 1 to Week 12
Outcome Measure
Number of Participants With AEs Leading to Study Drug Discontinuation in DBT Phase
Outcome Description
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 did not necessarily have a causal relationship with this treatment. In this outcome measure, participants with adverse events leading to study drug discontinuation were reported.
Outcome Time Frame
OLE: From Week 12 to Week 24
Outcome Measure
Number of Participants With AEs Leading to Study Drug Discontinuation in OLE Phase
Outcome Description
The laboratory parameters were graded according to the National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 and using division of AIDS (DAIDS) toxicity grading scale version 2.1 (glucose, low density lipoprotein \[LDL\] cholesterol, uric acid and urinalysis) and for other parameters (eosinophils, hemoglobin, leukocytes, albumin, lymphocytes, neutrophils, platelets, alanine aminotransferase, alkaline phosphatase ,aspartate aminotransferase, bicarbonate, bilirubin, calcium, cholesterol, creatine kinase, creatinine, lactate dehydrogenase, potassium, sodium, triglycerides) CTCAE version v5.0 was used. Severity were graded as Grade 1=mild AE, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants according to Grade 3 or 4 laboratory abnormalities are reported. Only laboratory abnormalities with non-zero values in any of the treatment arms are reported.
Outcome Time Frame
DBT: From Week 1 to Week 20
Outcome Measure
Number of Participants With Grade 3 to 4 Laboratory Abnormalities in DBT Phase
Outcome Description
The laboratory parameters were graded according to the NCI CTCAE version 5.0 and using DAIDS toxicity grading scale version 2.1 (glucose, LDL cholesterol, uric acid and urinalysis). And for other parameters (eosinophils, hemoglobin, leukocytes, albumin, lymphocytes, neutrophils, platelets, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, calcium, cholesterol, creatine kinase, creatinine, lactate dehydrogenase, potassium, sodium, triglycerides) CTCAE version v5.0 was used. Severity was graded as Grade 1=mild AE, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening consequences; urgent intervention indicated. Number of participants according to Grade 3 or 4 laboratory abnormalities are reported. Only laboratory abnormalities with non-zero values in any of the treatment arms are reported.
Outcome Time Frame
OLE: From Week 12 to Week 32
Outcome Measure
Number of Participants With Grade 3 to 4 Laboratory Abnormalities in OLE Phase
Outcome Description
Number of participants with AST or ALT \>3\*ULN concurrent with TBL \>2\*ULN in DBT phase were reported in this outcome measure.
Outcome Time Frame
DBT: From Week 1 to Week 20
Outcome Measure
Number of Participants With Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Elevations > 3* Upper Limit of Normal (ULN) Concurrent With (Total Bilirubin) TBL >2*ULN in DBT Phase
Outcome Description
Number of participants with AST or ALT \>3\*ULN concurrent with TBL \>2\*ULN in DBT phase were reported in this outcome measure.
Outcome Time Frame
OLE: From Week 12 to Week 32
Outcome Measure
Number of Participants With AST or ALT Elevations > 3* ULN Concurrent With TBL >2*ULN in OLE Phase
Outcome Description
\\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 did not necessarily have a causal relationship with this treatment. Hepatic-related AEs included: alanine aminotransferase and aspartate aminotransferase increased, liver function test abnormal, liver function test increased, bilirubin conjugated increased, blood bilirubin increased, transaminases increased and hyperbilirubinemia. Number of participants with any hepatic-related AEs in the DBT phase were reported in this outcome measure.
Outcome Time Frame
DBT: From Week 1 to Week 20
Outcome Measure
Number of Participants With Hepatic-Related AEs in the DBT Phase
Outcome Description
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 did not necessarily have a causal relationship with this treatment. Hepatic AEs included: alanine aminotransferase and aspartate aminotransferase increased, liver function test abnormal, bilirubin conjugated, hepatic enzyme increased, blood bilirubin unconjugated increased, blood bilirubin and transaminases increased and hepatic function abnormal. Number of participants with any hepatic-related AEs in the OLE phase were reported in this outcome measure.
Outcome Time Frame
OLE: From Week 12 to Week 32
Outcome Measure
Number of Participants With Hepatic-Related AEs in the OLE Phase
Outcome Description
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 did not necessarily have a causal relationship with this treatment. Hepatic-related AEs included: alanine aminotransferase and aspartate aminotransferase increased, liver function test and blood bilirubin increased. Number of participants with any hepatic-related AEs leading to study drug discontinuation is reported in this outcome measure.
Outcome Time Frame
DBT: From Week 1 to Week 12
Outcome Measure
Number of Participants With Hepatic-Related AEs Leading to Study Drug Discontinuation in the DBT Phase
Outcome Description
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 did not necessarily have a causal relationship with this treatment. Hepatic-related AEs included: aspartate aminotransferase increased and liver function test abnormal. Number of participants with any hepatic-related AEs leading to study drug discontinuation is reported in this outcome measure.
Outcome Time Frame
OLE: From Week 12 to Week 24
Outcome Measure
Number of Participants With Hepatic-Related AEs Leading to Study Drug Discontinuation in the OLE Phase
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jelena Pavlovic
Investigator Email
jpavlovi@montefiore.org
Categories Mesh Debug
Brain, Spinal Cord & Nervous System --- MIGRAINE DISORDERS
Headaches & Migraine --- MIGRAINE DISORDERS
Brain, Spinal Cord & Nervous System --- HEADACHE DISORDERS, PRIMARY
Headaches & Migraine --- HEADACHE DISORDERS, PRIMARY
Brain, Spinal Cord & Nervous System --- HEADACHE DISORDERS
Headaches & Migraine --- HEADACHE DISORDERS
Alzheimer's --- BRAIN DISEASES
Brain, Spinal Cord & Nervous System --- BRAIN DISEASES
Brain, Spine & Nerve Cancers --- BRAIN DISEASES
Alzheimer's --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- NERVOUS SYSTEM DISEASES
MeSH Terms
MIGRAINE DISORDERS
HEADACHE DISORDERS, PRIMARY
HEADACHE DISORDERS
BRAIN DISEASES
CENTRAL NERVOUS SYSTEM DISEASES
NERVOUS SYSTEM DISEASES
RIMEGEPANT SULFATE