Migraine
Conditions
Keywords
Migraine Prevention, Headache, Headache Prevention, Migraine Prevention in adults with inadequate response to oral preventative medications
Brief summary
This study is being conducted to evaluate the efficacy and tolerability of rimegepant for migraine prophylaxis in adults with a history of inadequate response to oral preventive medications
Interventions
DRUGRimegepant
Rimegepant 75 mg Oral Disintegrating Tablet (ODT) taken every other day during Double-blind Treatment (DBT) phase
DRUGPlacebo
Matching placebo with every other day dosing during DBT phase
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Migraine attacks present for more than 1 year with the age of onset prior to 50 years of age. 2. Migraine attacks, on average, lasting about 4 - 72 hours, if untreated. 3. 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). 4. Less than15 headache days (migraine or non-migraine) per month in each of the 3-months prior to the Screening Visit and throughout the Screening Phase. 5. Subjects must be able to distinguish migraine attacks from tension/cluster headaches. Prior inadequate response, within 10 years of the Screening Visit, to agents across 2-4 categories of recognized, orally-administered, migraine-preventive medications where at least one example of prior inadequate response is due to lack of efficacy or prior intolerance (not contraindication).
Exclusion criteria
1. History of cluster headaches, basilar migraine (migraine with brainstem aura), or hemiplegic migraine. 2. Current medication overuse headaches. 3. 15 or more headache days (migraine or non-migraine) per month in any of the 3-months prior to the Screening Visit or during the first 28- days of the Observation Phase. 4. Inadequate response (due to lack of efficacy, prior intolerance, or contraindication) to agents across \> 4 categories of recognized, orally administered, migraine-preventive medications. 5. Active chronic pain syndrome (such as fibromyalgia, chronic pelvic pain, complex regional pain syndrome \[CRPS\]). 6. 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 |
|---|---|---|
| Mean Change From Observation Phase (OP) in the Number of Migraine Days Per Month Over the Entire DBT Phase (Weeks 1 to 12) | Observation phase (28 days prior to randomization), DBT phase (through Month 3 [Week 1 to 12]) | A migraine day was defined as any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of migraine days per month were prorated to 28 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With >= 50 Percent (%) Reduction From OP in the Number of Moderate or Severe Migraine Days (MD) Per Month Over the Entire DBT Phase (Weeks 1 to 12) | DBT phase (through Month 3 [Week 1 to 12]) | Moderate or severe MD: a MD of moderate or severe headache pain intensity. MD: any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. Qualified migraine headache: migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of moderate or severe MD per month were prorated to 28 days and derived from data in the on-DBT efficacy analysis period as follows: 28\*(total number of moderate or severe MD through Month 3 \[Weeks 1 to 12\])/(total number of e-diary efficacy data days through Month 3 \[Weeks 1 to 12\]). |
| Mean Change From OP in the Number of Migraine Days Per Month in the First 4 Weeks (Weeks 1 to 4) of the DBT Phase | Observation phase (28 days prior to randomization), Week 1 to Week 4 of the DBT phase | A migraine day was defined as any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of migraine days per month were prorated to 28 days. |
| Mean Change From OP in the Number of Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of the DBT Phase | Observation phase (28 days prior to randomization), Week 9 to Week 12 of the DBT phase | A migraine day was defined as any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of migraine days per month were prorated to 28 days. |
| Mean Change From Baseline in the Migraine-Specific Quality-of-Life Questionnaire (MSQ) Version 2.1 Restrictive Role Function Domain Score at Week 12 of the DBT Phase | Baseline (Day 1) and Week 12 of the DBT phase | MSQ version 2.1 was a self-administered, 14-item instrument validated in 3 domains: role function-restrictive (7 items), role function-preventive (4 items), emotional function (3 items). The restrictive role function domain consisted of 7 items that described how migraine limited one's daily social and work-related activities. Each item was scored on 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. |
| Mean Change From Baseline in the Migraine Interictal Burden Scale (MIBS) Score at Week 12 of the DBT Phase | Baseline (Day 1) and Week 12 | MIBS was a 4-item self-administered questionnaire that measures: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Each item was rated on a 6-point scale as: don't know/ not applicable; never; rarely; some of the time; much of the time; most or all of the time. The MIBS score was the weighted sum of the item scores and ranged from 0 to 12. Higher scores indicated a greater impact of headaches on the participant's life between headache attacks. |
| Number of Participants With Any Adverse Events (AEs) by Worst Intensity in the DBT Phase. | DBT Phase: From Day 1 to Week 12 | 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. AE intensity included mild, moderate and severe, where Mild: usually transient and required only minimal treatment or therapeutic intervention. Event did not generally interfere with usual activities of daily living. Moderate: usually alleviated with additional specific therapeutic intervention. Event interfered with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to participant. Severe: interrupted usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. Participants were counted once in each intensity category based on greatest intensity of unique adverse event preferred terms. |
| Number of Participants With Any AEs by Worst Intensity in the OLE Phase | OLE Phase: From Week 12 to Week 24 | 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. AE intensity included mild, moderate and severe, where Mild: usually transient and required only minimal treatment or therapeutic intervention. Event did not generally interfere with usual activities of daily living. Moderate: usually alleviated with additional specific therapeutic intervention. Event interfered with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to participant. Severe: interrupted usual activities of daily living, significantly affected clinical status, or required intensive therapeutic intervention. Participants were counted once in each intensity category based on greatest intensity of unique adverse event preferred terms. |
| Number of Participants With Serious AEs (SAEs) in the DBT Phase | DBT Phase: From Day 1 to Week 12 | A serious adverse event (SAE) was any event that met any of the following criteria at any dose: 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 and other important medical events. |
| Number of Participants With SAEs in the OLE Phase | OLE Phase: From Week 12 to Week 24 | A SAE was any event that met any of the following criteria at any dose: 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 and other important medical events. |
| Number of Participants With AEs Leading to Study Drug Discontinuation in the DBT Phase | DBT Phase: From Day 1 to Week 12 | 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 AEs leading to discontinuation of study drug were reported. |
| Number of Participants With AEs Leading to Study Drug Discontinuation in the OLE Phase | OLE Phase: From Week 12 to Week 24 | 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 AEs leading to discontinuation of study drug were reported. |
| Number of Participants With Grade 3 to 4 Laboratory Abnormalities: DBT Phase | DBT Phase: From Day 1 to Week 12 | 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. Only those Grade 3 or 4 laboratory tests with non-zero values in any of treatment arms are reported in this outcome measure. |
| Number of Participants With Grade 3 to 4 Laboratory Abnormalities: OLE Phase | OLE Phase: From Week 12 to Week 24 | Laboratory tests included hematology and serum chemistry. All laboratory tests except glucose were graded according to NCI CTCAE v5.0, 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. Only those Grade 3 or 4 laboratory tests with non-zero values in any of treatment arms are reported in this outcome measure. |
| Percentage of Participants With >= 50% Reduction From OP in the Number of Migraine Days Per Month (Regardless of Pain Intensity) Over the Entire DBT Phase (Weeks 1 to 12) | DBT phase (through Month 3 [Week 1 to 12]) | A migraine day was defined as any calendar day in which participant (1) had a qualified migraine headache or (2) took acute migraine-specific medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. A qualified migraine headache was defined as a migraine with or without aura, lasting for \>=30 minutes, met criteria: \>=2 of pain features: unilateral location; pulsating quality (throbbing); moderate or severe pain intensity; aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) or \>=1 of associated symptoms: nausea and/or vomiting; photophobia and phonophobia. Number of migraine days per month were prorated to 28 days and derived from data in the 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 Number of Acute Migraine-Specific Medication Days Per Month in Each Month and Over the Entire DBT Phase (Weeks 1 to 12) | DBT phase Months 1, 2 and 3; overall DBT through Month 3 (Week 1 to 12) | An acute migraine-specific medication day was defined as any calendar day during which a participant took a migraine-specific acute migraine medication (i.e., triptan, ergotamine, lasmiditan, or ubrogepant) to treat headache or aura. The number of acute migraine-specific medication days per month were prorated to 28 days. |
| Mean Change From Baseline in MIBS Scores at Weeks 4, 8, and 12 in the DBT Phase | DBT Phase: Baseline (Day 1), Weeks 4, 8, and 12 | MIBS was a 4-item self-administered questionnaire that measures: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Each item was rated on a 6-point scale as: don't know/ not applicable; never; rarely; some of the time; much of the time; most or all of the time. The MIBS score was the weighted sum of the item scores and ranged from 0 to 12. Higher scores indicated a greater impact of headaches on the participant's life between headache attacks. |
| Mean Change From Baseline in MSQ Domain Scores at Weeks 4, 8, and 12 in the DBT Phase | DBT Phase: Baseline (Day 1), Weeks 4, 8, and 12 | MSQ was a self-administered, 14-item instrument validated in 3 domains: role function-restrictive (7 items), role function-preventive (4 items), emotional function (3 items). Each item was scored on 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 domain scores are computed as a sum of item responses and rescaled to a 0 to 100 scale such that lower score (0) indicated poor quality of life and higher scores (100) indicated better quality of life. |
| Mean Change From Baseline in Migraine Functional Impact Questionnaire (MFIQ) Domain Scores in Each Month of the DBT Phase | DBT Phase: Baseline (Day 1), Months 1, 2, and 3 | MFIQ was a 26-item participant-report questionnaire. It is designed to measure the subjective impact of migraine on physical, social, and emotional functioning over 5 domains: physical function (5 items), usual activities (10 items), social function (5 items), emotional function (5 items) and overall impact on usual activities (16 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the past 7 days. |
| Change From Baseline in Work Productivity and Activity Impairment (WPAI) - Migraine Absenteeism Scores at Weeks 4, 8, and 12 in the DBT Phase | DBT Phase: Baseline (Day 1), Weeks 4, 8, and 12 | The WPAI was a 6-item participant-administered questionnaire used to capture work impairment due to migraine pain. The questions are as follows: Q1 = currently employed (yes/no); Q2 = hours missed due to health problems; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, with higher numbers indicating less productivity); Q6 = degree health affected regular activities (0-10 scale, with higher numbers indicating greater impairment of regular activities). The absenteeism score was calculated from Q2 and Q4 for participants who responded "yes" to Q1 and ranged from 0 to 100 with higher score indicating greater impairment and less productivity. |
| Change From Baseline in WPAI - Migraine Presenteeism Scores at Weeks 4, 8, and 12 in the DBT Phase | DBT Phase: Baseline (Day 1), Weeks 4, 8, and 12 | The WPAI was a 6-item participant-administered questionnaire used to capture work impairment due to migraine pain. The questions are as follows: Q1 = currently employed (yes/no); Q2 = hours missed due to health problems; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, with higher numbers indicating less productivity); Q6 = degree health affected regular activities (0-10 scale, with higher numbers indicating greater impairment of regular activities). The presenteeism score was calculated using Q5 for participants who responded "yes" to Q1 and had Q4\>0 and ranged from 0 to 100 with higher score indicating greater impairment and less productivity. |
| Change From Baseline in WPAI - Migraine Work Productivity Loss Scores at Weeks 4, 8, and 12 in the DBT Phase | DBT Phase: Baseline (Day 1), Weeks 4, 8, and 12 | The WPAI was a 6-item participant-administered questionnaire used to capture work impairment due to migraine pain. The questions are as follows: Q1 = currently employed (yes/no); Q2 = hours missed due to health problems; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, with higher numbers indicating less productivity); Q6 = degree health affected regular activities (0-10 scale, with higher numbers indicating greater impairment of regular activities). The work productivity loss score was calculated using Q2, Q4, and Q5 for participants who responded "yes" to Q1 and ranged from 0 to 100 with higher score indicating greater impairment and less productivity. |
| Change From Baseline in WPAI - Migraine Activity Impairment Scores at Weeks 4, 8, and 12 in the DBT Phase | DBT Phase: Baseline (Day 1), Weeks 4, 8, and 12 | The WPAI was a 6-item participant-administered questionnaire used to capture work impairment due to migraine pain. The questions are as follows: Q1 = currently employed (yes/no); Q2 = hours missed due to health problems; Q3 = hours missed due to other reasons; Q4 = hours actually worked; Q5 = degree health affected productivity while working (0-10 scale, with higher numbers indicating less productivity); Q6 = degree health affected regular activities (0-10 scale, with higher numbers indicating greater impairment of regular activities). The activity impairment score was calculated using Q6 and ranged from 0 to 100 with higher score indicating greater impairment and less productivity. |
| Mean Change From Baseline in Patient Global Assessment (PGA) Score in Each Month of the DBT Phase | DBT Phase: Baseline (Day 1), Months 1, 2, and 3 | The PGA scale was a single item assessment that measured the participant's overall assessment of migraine on a 5-point scale as: (1) very good: asymptomatic and no limitation of normal activities; (2) good: mild symptoms and no limitation of normal activities; (3) fair: moderate symptoms and limitation of some normal activities; (4) poor: severe symptoms and inability to carry out most normal activities; (5) very poor: very severe symptoms which are intolerable and inability to carry out all normal activities. Lower scores indicated fewer symptoms and less disability to carry out normal activities. |
Countries
Australia, Austria, Belgium, Canada, Denmark, Finland, Germany, Italy, Mexico, Poland, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Pre-assignment details
A total of 962 participants signed the informed consent form and were enrolled in the study. Of the enrolled participants, 658 participants were randomized in the study and 304 were not randomized (due to failure to meet eligibility criteria at screening \[282 participants\], withdrawal of consent \[21 participants\], or adverse event \[1 participant\]).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41.98 Years STANDARD_DEVIATION 11.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 33 Participants |
| Sex: Female, Male Female | 561 Participants |
| Sex: Female, Male Male | 39 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 328 | 0 / 324 | 0 / 301 | 0 / 294 | 0 / 308 | 0 / 296 |
| other Total, other adverse events | 43 / 328 | 51 / 324 | 22 / 301 | 12 / 294 | 1 / 308 | 2 / 296 |
| serious Total, serious adverse events | 1 / 328 | 5 / 324 | 2 / 301 | 4 / 294 | 1 / 308 | 2 / 296 |
Outcome results
None listed