Migraine
Conditions
Keywords
Migraine, Acute Migraine, Headache, Acute treatment of Migraine in adults unsuitable for triptans
Brief summary
This study is being conducted to evaluate the efficacy and tolerability of rimegepant in a population of adults that are unsuitable for triptan medications due to a previous intolerance, lack of efficacy, or contraindication (including a history of clinically-relevant cardiovascular disease).
Detailed description
This study is being conducted to evaluate the efficacy and tolerability of rimegepant in a population of adults that are unsuitable for triptan medications due to a previous intolerance, lack of efficacy, or contraindication (including a history of clinically-relevant cardiovascular disease). Rimegepant will be further evaluated in this population with as needed use in a 12-week, open-label extension study.
Interventions
DRUGRimegepant
DB Phase: Rimegepant 75 mg Orally Disintegrating Tablet (ODT)
DRUGPlacebo
DB Phase: matching placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
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
* Migraine attacks present for more than 1 year with the age of onset prior to 50 years of age. * Migraine attacks, on average, lasting about 4 - 72 hours if untreated. * 4 to 14 migraine days per month on average across the 3 months prior to the Screening Visit (month is defined as 28 days for the purpose of this protocol). * Less than 15 headache days (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and throughout the Screening Phase. * Subjects must be able to distinguish migraine attacks from tension/cluster headaches. * Subjects on prophylactic migraine medication (excluding CGRP antagonists) are permitted to remain on therapy if they have been on a stable dose for at least 3 months (12 weeks) prior to the Screening Visit, and if the dose is not expected to change during the course of the study. * Triptan unsuitable
Exclusion criteria
-Target Disease Exclusion: 1. History of cluster headache, basilar migraine, or hemiplegic migraine 2. Current medication overuse headaches 3. Headaches occurring 15 or more days per month (migraine or non-migraine) in any of the 3 months prior to the Screening Visit 4. Active chronic pain syndrome (such as fibromyalgia, chronic pelvic pain, complex regional pain syndrome \[CRPS\]) 5. Other pain syndromes (including trigeminal neuralgia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, interfere with study assessments of safety or efficacy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pain Relief at 2 Hours Post-Dose: DBT Phase | At 2 hours post-dose | Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Pain relief at 2 hours post-dose was defined as pain intensity of none or mild at that time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pain Freedom at 2 Hours Post-Dose: DBT Phase | At 2 hours post-dose | Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). Pain freedom at 2 hours post-dose was a pain intensity of none at that time point. |
| Percentage of Participants Who Used Rescue Medications Within 24 Hours Post-Dose: DBT Phase | Within 24 hours post-dose | Post 24 hours after dosing with study medication and after the 24-hour assessments were completed on the e-diary, participants were permitted to use the following rescue medications (non-study medications) such as: 1) non-steroidal anti-inflammatory drug like acetaminophen or aspirin, ibuprofen, naproxen; 2) antiemetics like metoclopramide, promethazine; 3) other like baclofen; 4) other approved pharmacological treatment with established efficacy in the acute treatment of migraine, including locally recognized standard of care, unless otherwise specified. |
| Percentage of Participants With Return to Normal Function at 2 Hours Post-Dose: DBT Phase | At 2 hours post-dose | Functional disability level was measured on a 4-point numeric rating scale (0= normal,1= mildly impaired, 2= severely impaired, 3= required bedrest). Functional disability was defined as a functional disability level of mildly impaired, severely impaired, or required bedrest. Return to normal function at 2 hours post-dose was defined as functional disability score of normal at that time point for participants with functional disability at the time of dosing. |
| Percentage of Participants With Sustained Return to Normal Function From 2 to 24 Hours Post-Dose: DBT Phase | From 2 to 24 hours post-dose | Functional disability level was measured on a 4-point numeric rating scale (0= normal,1= mildly impaired, 2= severely impaired, 3= required bedrest). Functional disability was defined as a functional disability level of mildly impaired, severely impaired, or required bedrest. Sustained return to normal function, from 2 to 24 hours post-dose was defined as functional disability levels of normal at all time points from 2 to 24 hours post-dose in participants with functional disability at the time of dosing. |
| Percentage of Participants With Sustained Return to Normal Function From 2 to 48 Hours Post-Dose: DBT Phase | From 2 to 48 hours post-dose | Functional disability level was measured on a 4-point numeric rating scale (0= normal,1= mildly impaired, 2= severely impaired, 3= required bedrest). Functional disability was defined as a functional disability level of mildly impaired, severely impaired, or required bedrest. Sustained return to normal function, from 2 to 48 hours post-dose was defined as functional disability levels of normal at all time points from 2 to 48 hours post-dose in participants with functional disability at the time of dosing. |
| Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-Dose: DBT Phase | From 2 to 24 hours post-dose | Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). 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. |
| Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-Dose: DBT Phase | From 2 to 48 hours post-dose | Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). 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. |
| Percentage of Participants With Sustained Freedom From Pain From 2 to 24 Hours Post-Dose: DBT Phase | From 2 to 24 hours post-dose | Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). 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. |
| Percentage of Participants With Sustained Freedom From Pain From 2 to 48 Hours Post-Dose: DBT Phase | From 2 to 48 hours post-dose | Participants recorded their migraine headache pain intensity using 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe). 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. |
| Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-Dose: DBT Phase | At 2 hours post-dose | MBS freedom was defined as MBS reported before dosing that was absent post-dose at the specified time point. MBS reported before dosing was nausea, photophobia, or phonophobia. Each symptom (nausea, photophobia, or phonophobia) was measured post-dose using 0= absent or 1= present. Participants who had symptom score of 0 (absent) aligning with MBS reported before dosing were considered to have MBS freedom. |
| Reliability of Rimegepant Effect in the OLE Phase Based on Evaluable Qualifying Migraine Attacks (EQMA) of DBT and OLE Phase | DBT phase: up to maximum 45 days; OLE phase: up to maximum of 12 weeks | Reliability of rimegepant effect during OLE Phase achieved when difference between (1) percentage of participants randomized to rimegepant with response to single EQMA in DBT phase and(2) percentage of participants with response to \>=4 of first 5 EQMAs \>=23 hours(h) apart in OLE phase was \<=7%. Statistical analysis reports difference between (1) and (2) for each first 5 EQMAs \>=23h apart in OLE phase. Response: category of "moderately better" or"very much better" for Migraine Quality of Life Questionnaire(MQoL)Question(Q) 16 (overall change in migraine symptoms since taking study medication) at 24h post-dose. EQMA:evaluable qualifying migraine attack (migraine attack of moderate/severe pain intensity,first treated with rimegepant, not other acute headache medication) with nonmissing MQoL Q16 value at 24h post dose. Percentage of participants with response after single EQMA in DBT phase randomized to rimegepant and each of first 5 EQMA in OLE phase are reported in descriptive section. |
| Mean Change From Historical Baseline in Number of Migraine Days Per Month by Headache Pain Intensity at Months 1, 2 and 3 and Overall: OLE Phase | Baseline (3 months prior to Screening); Month 1 (OLE Days 1 to 28), Month 2 (OLE Days 29 to 56) and Month 3 (OLE Days 57 to 84), and Overall OLE phase (84 days) | Mean change from historical baseline in the number of migraine days per month by headache pain intensity (total; moderate or severe) at each specified month and over the entire OLE Phase is reported in this outcome measure. A migraine day was defined as either 1) a day on which participant experienced migraine headache pain intensity of mild, moderate, or severe as reported in eDiary or 2) an acute migraine-specific medication day. Total historical baseline is defined as the number of migraine days per month of any pain intensity in the 3 months prior to screening from the migraine history case report form (CRF). Moderate or severe historical baseline was defined as the number of migraine days per month of moderate or severe pain intensity in the 3 months prior to screening from the migraine history CRF. |
| Percentage of Participants With at Least 50% Reduction From Historical Baseline in the Number of Migraine Days Per Month by Headache Pain Intensity at Months 1, 2 and 3 and Overall: OLE Phase | Baseline (3 months prior to Screening); Month 1 (OLE Days 1 to 28), Month 2 (OLE Days 29 to 56) and Month 3 (OLE Days 57 to 84), and Overall OLE phase (84 days) | Percentages of participants with \>= 50% reduction from historical baseline in the number of migraine days per month by headache pain intensity (total; moderate or severe) in each month and over the entire OLE Phase is reported in this outcome measure. A migraine day was defined as either 1) a day on which participant experienced migraine headache pain intensity of mild, moderate, or severe as reported in eDiary or 2) an acute migraine-specific medication day. Total historical baseline is defined as the number of migraine days per month of any pain intensity in the 3 months prior to screening from the migraine history CRF. Moderate or severe historical baseline was defined as the number of migraine days per month of moderate or severe pain intensity in the 3 months prior to screening from the migraine history CRF. |
| Number of Participants With Adverse Events (AEs) by Intensity: DBT Phase | DBT Phase: maximum of 45 days | 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 was defined as AEs which is usually transient and required only minimal treatment or therapeutic intervention. The event did not generally interfere with usual activities of daily living. Moderate AE was defined as AEs which was 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 was defined as AE that interrupted with usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. |
| Number of Participants With Serious AEs: DBT Phase | DBT Phase: maximum of 45 days | 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. A serious AE is 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 a participant who received rimegepant or other important medical events. |
| Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase | DBT Phase: maximum of 45 days | 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. Number of participants with AEs leading to study drug discontinuation have been reported in this outcome measure. |
| Number of Participants With Any On-Treatment Grade 3 to 4 Laboratory Abnormalities: DBT Phase | DBT Phase: maximum of 45 days | Laboratory tests included hematology and serum chemistry. All laboratory tests except glucose were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0, where Grade 3=severe events which require hospitalization or prolongation of hospitalization and Grade 4=life-threatening consequences requiring urgent intervention. Glucose was graded according to Division of Acquired Immune Deficiency Syndrome table for Grading Severity of Adult and Pediatric Adverse Events v2.1. |
| Number of Participants With AEs by Intensity: OLE Phase | OLE Phase: maximum up to 12 weeks | 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 was defined as AEs which is usually transient and required only minimal treatment or therapeutic intervention. The event did not generally interfere with usual activities of daily living. Moderate AE was defined as AEs which was 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 was defined as AE that interrupted with usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. |
| Number of Participants With Serious AEs: OLE Phase | OLE Phase: maximum up to 12 weeks | 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. A serious AE is 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 a participant who received rimegepant or other important medical events. |
| Number of Participants With AEs Leading to Study Drug Discontinuation: OLE Phase | OLE Phase: maximum up to 12 weeks | 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. Number of participants with AEs leading to study drug discontinuation have been reported in this outcome measure. |
| Number of Participants With On-Treatment Grade 3 to 4 Laboratory Abnormalities: OLE Phase | OLE Phase: maximum up to 12 weeks | Laboratory tests included hematology and serum chemistry. All laboratory tests except glucose were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0, where Grade 3=severe events which require hospitalization or prolongation of hospitalization and Grade 4=life-threatening consequences requiring urgent intervention. Glucose was graded according to Division of Acquired Immune Deficiency Syndrome table for Grading Severity of Adult and Pediatric Adverse Events v2.1. |
| Mean Change From Baseline in the Migraine Interictal Burden Scale (MIBS) Score at Weeks 4, 8, and 12: OLE Phase | OLE phase: Baseline; Week 4, Week 8 and Week 12 | MIBS was a 4-item self-administered questionnaire that measured interictal migraine related burden in the past 4 weeks on days when participants were not having an attack, using 4 domains: impairment in work or school; impairment in family and social life; difficulty making plans or commitments; emotional/affective and cognitive distress. The questionnaire specifically asked about the effect of the disease over the past 4 weeks on days without a headache attack. Response options included: don't know/not applicable (0), never (0), rarely (1), some of the time (2), much of the time (3), or most or all of the time (3). Each response associated with numerical score were summed across all 4 items resulting in a total MIBS score ranging from 0 to 12, and the level of interictal burden being categorized into the following: 0 for none and 12 for severe. Higher scores indicate worse interictal burden. |
Countries
Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Italy, Mexico, Poland, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
A total of 813 participants were enrolled in the study, out of these 180 participants were not randomized. Only 633 participants were randomized. A total of 585 participants were treated with study intervention in double-blind treatment (DBT) phase. Then, 555 participants continued into open label extension (OLE) phase.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 42.7 Years STANDARD_DEVIATION 11.5 |
| Race/Ethnicity, Customized Black or African American | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 8 Participants |
| Race/Ethnicity, Customized Multiracial | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 46 Participants |
| Race/Ethnicity, Customized White | 45 Participants |
| Sex: Female, Male Female | 260 Participants |
| Sex: Female, Male Male | 29 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 / 295 | 0 / 290 | 0 / 253 | 0 / 244 | 0 / 281 | 0 / 271 | 0 / 283 | 0 / 267 |
| other Total, other adverse events | 116 / 295 | 20 / 290 | 0 / 253 | 0 / 244 | 68 / 281 | 56 / 271 | 67 / 283 | 55 / 267 |
| serious Total, serious adverse events | 0 / 295 | 0 / 290 | 0 / 253 | 0 / 244 | 1 / 281 | 1 / 271 | 1 / 283 | 2 / 267 |
Outcome results
None listed