Migraine
Conditions
Keywords
Rimegepent, preventive treatment, migraine.
Brief summary
The purpose of this study is to learn about the effects of Rimegepant to help prevent migraine. This study is seeking for participants who: * Are male and female of 18 years of age or older. * Have at least 1 year history of migraine . * Did not take any medication for migraine before the start of this study. The study will go on for around 30 weeks, including 4 Phases and 11 Visits. Participants who are selected for the study will be randomly assigned to treatment groups. After which, the participants will enter a 12-week Double-blind Treatment (DBT) Phase. After finishing the DBT Phase, some selected participants may enter a 12-week Open-label Extension (OLE) Phase. Participants will come back to the study site at the end of Week 24 for the End of Treatment (EOT) Visit. There will be a follow-up Week 2 Visit around 14 days after the EOT visit. Participants will be asked to take 1 tablet of study medicine every other calendar day. This need to be followed regardless of whether they have a migraine on that day or not. During the OLE Phase only, if a participant has a migraine on a non-scheduled dosing day, they may take 1 tablet of Rimegepant orally disintegrating tablet (ODT) as acute treatment for their migraine, if needed, with a maximum of 1 tablet of Rimegepant per calendar day. The study team will look at how each participant is doing with the study treatment during the regular visits at the study clinic.
Interventions
DRUGRimegepant
Rimegepant
DRUGPlacebo
matching placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1.Target Population: Participant 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: 1. Age of onset of migraines prior to 50 years of age 2. Migraine attacks, on average, lasting 4 to 72 hours if untreated 3. Per participant 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. 6 or more migraine days during Observation Phase 5. Not more than 18 headache days during the Observation Phase 6. Ability to distinguish migraine attacks from tension/cluster headaches. 7. Participants with contraindications for use of triptans may be included provided they meet all other study entry criteria.
Exclusion criteria
1. Participant has a history of basilar migraine or hemiplegic migraine. 2. Participants are excluded if they have had no therapeutic response with \> 2 of the 9 medication categories of preventive treatment of migraine after an adequate therapeutic trial in the past 3 years per investigator's judgement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From the Observation Phase (OP) in Number of Migraine Days Per Month Over the Entire DBT Phase (Weeks 1 to 12) | OP (screening of 4 weeks prior to randomization), DBT phase (Weeks 1 to 12) | A migraine day(MD) was defined as any calendar day participant experienced a qualified migraine headache (onset,continuation,or recurrence), per electronic diary(eDiary). A qualified migraine headache was defined as a migraine with/without aura,lasted for \>=30 minutes with \>=2 pain features (unilateral location,pulsating quality\[throbbing\],moderate/severe pain intensity,aggravated by or caused avoidance of routine physical activity \[e.g. walking/climbing stairs\]) and/or with \>=1 of the following associated symptoms (nausea and/or vomiting, both photophobia and phonophobia).The number(no.) of md per month (m) was prorated to 28 days and derived as:OP:28\*\[total no.of MD in OP analysis period\]/(total no.of efficacy data day in OP analysis period), monthly (4-week interval) on-DBT efficacy analysis period: 28\*(total no.of MD in m)/(total no. of efficacy data days in m),overall DBT in on-DBT efficacy analysis period:28\*(total no.of MD through m3)/(total no.of efficacy data day through m3). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With >=50% Reduction From the OP in the Number of Moderate to Severe Migraine Days Per Month Over the Entire DBT Phase (Weeks 1 to 12) | OP (screening of 4 weeks prior to randomization), DBT Phase (Weeks 1 to 12) | A MD was defined as any calendar day participant experienced a qualified migraine headache(onset,continuation,or recurrence),per eDiary. A qualified migraine headache was defined as a migraine with/without aura,lasted for \>=30 minutes with \>=2 pain features(unilateral location,pulsating quality \[throbbing\], moderate/severe pain intensity, aggravated by or caused avoidance of routine physical activity \[e.g. walking/climbing stairs\]) and/or with \>=1 of the following associated symptoms(nausea and/or vomiting, both photophobia and phonophobia).The number of MD per month was prorated to 28 days and derived as: OP: 28\*\[total number of MD in OP analysis period\]/(total number of efficacy data days in OP analysis period), monthly (4-week interval) on-DBT efficacy analysis period: 28\*(total number of MD in month)/(total number of efficacy data days in month),overall DBT in on-DBT efficacy analysis period:28\*(total number of MD through month 3)/(total no .of efficacy data days through month 3). |
| Mean Change From the OP in the Number of Migraine Days Per Month in the First 4 Weeks (Weeks 1 to 4) of the DBT Phase | OP (screening of 4 weeks prior to randomization), DBT phase (Weeks 1 to 4) | A MD was defined as any calendar day participant experienced a qualified migraine headache(onset,continuation,or recurrence),per eDiary. A qualified migraine headache was defined as a migraine with/without aura,lasted for \>=30 minutes with \>=2 pain features (unilateral location,pulsating quality\[throbbing\],moderate/severe pain intensity,aggravated by or caused avoidance of routine physical activity\[e.g. walking/climbing stairs\]) and/or with \>=1 of the following associated symptoms (nausea and/or vomiting, both photophobia and phonophobia).The number of MD per month was prorated to 28 days and derived as:OP:28\*\[total number of MD in OP analysis period\]/(total number of efficacy data days in OP analysis period), monthly (4-week interval) on-DBT efficacy analysis period: 28\*(total number of MD in month)/(total number of efficacy data days in month), overall DBT in on-DBT efficacy analysis period:28\*(total number of MD through month 3)/(total number of efficacy data days through month 3). |
| Mean Change From the OP in the Number of Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of the DBT Phase | OP (screening of 4 weeks prior to randomization), DBT phase (Weeks 9 to 12) | A MD was defined as any calendar day participant experienced a qualified migraine headache(onset,continuation,or recurrence),per eDiary. A qualified migraine headache was defined as a migraine with/without aura,lasted for \>=30 minutes with \>=2 pain features (unilateral location,pulsating quality\[throbbing\],moderate/severe pain intensity,aggravated by or caused avoidance of routine physical activity \[e.g. walking/climbing stairs\]) and/or with \>=1 of the following associated symptoms (nausea and/or vomiting, both photophobia and phonophobia).The number of MD per month was prorated to 28 days and derived as:OP:28\*\[total number of MD in OP analysis period\]/(total number of efficacy data days in OP analysis period), monthly (4-week interval) on-DBT efficacy analysis period: 28\*(total number of MD in month)/(total number of efficacy data days in month),overall DBT in on-DBT efficacy analysis period:28\*(total number of MD through month 3)/(total number of efficacy data days through month 3). |
| Mean Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire (MSQoL) Role Function-Restrictive Domain Score at Week 12 of the DBT Phase | Baseline, DBT phase (Week 12) | MSQoL:14-item instrument validated in 3 domains:restrictive role function,preventative role function and emotional function.Role function-restrictive domain consisted of 7 items that described how migraine limits one's daily social and work-related activities.Participants were required to respond to items using a 6-point scale ranging from 1-6, where 1=none of the time,2=little bit of the time,3=some of the time,4=good bit of the time,5=most of the time and 6=all of the time.Item scores were recorded using(7-original score).Raw dimension scores for restrictive role function domain were computed as a sum of recorded item scores(7-42) and rescaled from 0-100 scale such that lowest score(0) indicated poor quality of life(QOL) and highest scores(100) indicated better QOL.Change from baseline was calculated as MSQoL role function-restrictive domain score at Week 12 of DBT phase minus MSQoL role function-restrictive domain score at baseline.Data collected on Day 1 was referred to Baseline. |
| Mean Number of Acute Migraine Medication Days Per Month Over the Entire DBT Phase (Weeks 1 to 12) | DBT phase (Weeks 1 to 12) | Acute migraine-specific medication day was defined as any calendar day during which the participant took a migraine-specific medication (triptan). Acute migraine medication days were defined as either acute migraine-specific medication day or migraine day with "yes" response to the question about taking other medications to treat headache or aura. The number of migraine day per month was prorated to 28 days and derived as: OP: 28\*\[total number of migraine day in the OP analysis period\]/(total number of efficacy data days in the OP analysis period), monthly (i.e., 4-week interval) in the on-DBT efficacy analysis period: 28\*(total number of migraine day in the month)/(total number of efficacy data days in the month), overall DBT in the on-DBT efficacy analysis period: 28\*(total number of migraine day through month 3)/(total number of efficacy data days through month 3). |
| Number of Participants With Any On-Treatment Adverse Events (AEs) by Severity During the DBT Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 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 did not necessarily have a causal relationship with this treatment. AEs were graded per the common terminology criteria for adverse events (CTCAE) as grade 1 indicates mild AE, grade 2 indicates moderate AE, grade 3 indicates severe AE, grade 4 indicates life-threatening consequences and urgent intervention, and grade 5 indicates death related to AE. Number of participants who had grade 3 or 4 AEs were reported in this outcome measure. |
| Number of Participants With Serious Adverse Events (SAEs) On-Treatment During the DBT Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 weeks) | An SAE was any event that met any of the 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 were considered an important medical event. |
| Number of Participants With AEs Leading to Study Intervention Discontinuation During the DBT Phase | DBT phase: maximum of 12 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 AEs leading to discontinuation of study intervention during the DBT phase were reported. |
| Number of Participants With Any On-Treatment Grade 3 to 4 Laboratory Test Abnormalities During the DBT Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 weeks) | Laboratory test included hematology (hemoglobin, lymphocytes, white blood cell count \[high, low\], neutrophils and platelets), serum chemistry (alkaline phosphatase \[ALP\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], albumin, bilirubin, creatine kinase \[CK\], calcium \[high, low\], glucose fasting and non-fasting \[high, low\], cholesterol \[total\], glucose \[low\], creatinine, LDL cholesterol, potassium, sodium \[high, low\], triglycerides, uric acid \[urate\] and estimated glomerular filtration rate \[eGFR\] modification of diet in renal disease \[MDRD\]) and urinalysis (urine glucose and urine protein). Laboratory abnormalities were graded according to CTCAE as grade 3 indicates severe AE, grade 4 indicates life-threatening consequences and urgent intervention. Number of participants who had non-zero grade 3 to 4 laboratory test abnormalities were reported in this outcome measure. |
| Number of Participants With Any On-Treatment AEs by Severity During the OLE Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 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 did not necessarily have a causal relationship with this treatment. AEs were graded per the CTCAE as grade 1 indicates mild AE, grade 2 indicates moderate AE, grade 3 indicates severe AE, grade 4 indicates life-threatening consequences and urgent intervention, and grade 5 indicates death related to AE. Number of participants who had grade 3 or 4 AEs were reported in this outcome measure. |
| Number of Participants With SAEs On-Treatment During the OLE Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 weeks) | An SAE was any event that met any of the 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 were considered an important medical event. |
| Number of Participants With AEs Leading to Study Intervention Discontinuation on Treatment During the OLE Phase | OLE phase: maximum of 12 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 AEs leading to discontinuation of study intervention during the OLE phase were reported. |
| Number of Participants With Any On-Treatment Grade 3 to 4 Laboratory Test Abnormalities During the OLE Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 weeks) | Laboratory test included hematology (hemoglobin, lymphocytes, white blood cell count \[high, low\], neutrophils and platelets), serum chemistry (ALP, ALT, AST, albumin, bilirubin, CK, calcium \[high, low\], glucose fasting and non-fasting \[high, low\], cholesterol \[total\], glucose \[low\], creatinine, LDL cholesterol, potassium, sodium \[high, low\], triglycerides, uric acid \[urate\] and eGFR MDRD) and urinalysis (urine glucose and urine protein). Laboratory abnormalities were graded according to CTCAE as grade 3 indicates severe AE, grade 4 indicates life-threatening consequences and urgent intervention. Number of participants who had non-zero grade 3 to 4 laboratory test abnormalities were reported in this outcome measure. |
| Number of Participants With ALT or AST Elevations >3* Upper Limit of Normal (ULN) Concurrent With Total Bilirubin (TBL) Elevations >2*ULN On-Treatment During the DBT Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 weeks) | Number of participants with ALT or AST elevations \>3\*ULN concurrent with TBL elevations \>2\*ULN in DBT phase were reported in this outcome measure. |
| Number of Participants With ALT or AST Elevations >3*ULN Concurrent With TBL Elevations >2*ULN On-Treatment During the OLE Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 weeks) | Number of participants with ALT or AST elevations \>3\*ULN concurrent with TBL elevations \>2\*ULN in OLE phase were reported in this outcome measure. |
| Number of Participants With Hepatic-related AEs On-Treatment During the DBT Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 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 hepatic-related AEs during the DBT phase were reported. |
| Number of Participants With Hepatic-related AEs Leading to Study Intervention Discontinuation On-Treatment During the DBT Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 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 hepatic-related AEs leading to discontinuation of study intervention during the DBT phase were reported. |
| Number of Participants With Hepatic-related AEs On-Treatment During the OLE Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 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 hepatic-related AEs during the OLE phase were reported. |
| Number of Participants With Hepatic-Related AEs Leading to Study Intervention Discontinuation On-Treatment During the OLE Phase | From Day 1 up to 4 weeks post last dose (maximum up to 16 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 hepatic-related AEs leading to discontinuation of study intervention during the OLE phase were reported. |
Countries
China
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 37.5 Years STANDARD_DEVIATION 9.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 394 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 786 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 571 Participants |
| Sex: Female, Male Male | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 392 | 0 / 394 | 0 / 360 | 0 / 364 | 0 / 392 | 0 / 376 | 0 / 16 | 0 / 353 |
| other Total, other adverse events | 162 / 392 | 161 / 394 | 118 / 360 | 110 / 364 | 235 / 392 | 10 / 376 | 1 / 16 | 4 / 353 |
| serious Total, serious adverse events | 8 / 392 | 3 / 394 | 5 / 360 | 1 / 364 | 13 / 392 | 3 / 376 | 0 / 16 | 1 / 353 |
Outcome results
None listed