Acute Treatment of Migraine, Migraine
Conditions
Brief summary
The primary purpose of this study is to evaluate the efficacy of rimegepant (BMS-927711) compared with placebo in the acute treatment of migraine as measured by Pain Freedom (headache pain intensity level reported as no pain) at 2 hours post dose using a four point numeric rating scale (no pain, mild pain, moderate pain, severe pain) while identifying an optimal dose to support the Phase 3 clinical trials.
Detailed description
Intervention Model: Parallel Versus Comparator + Placebo
Interventions
DRUGRimegepant
Rimegepant capsules
DRUGPlacebo
Rimegepant placebo-matching capsules
DRUGSumatriptan
Rimegepant matching sumatriptan and Rimegepant matching placebo capsules
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patient with at least 1-year history of migraines (with or without aura) including the following: * Migraine attacks more than 1 year with age of onset prior to 50 years of age * Migraine attacks, on average, last about 4 - 72 hours if untreated * No more than 8 attacks of moderate to severe intensity per month within last 3 months * Patient must be able to distinguish migraine attacks from tension/cluster attacks and must have consistent migraine headaches of at least 2 migraine headaches attacks of moderate to severe intensity in each of the last 3 months * Less than 15 days of headache (migraine or non-migraine) per month in each of 3 months prior to screening * Male and female ≥ 18 years and ≤ age 65 * No clinically significant abnormality identified on the medical or laboratory evaluation Key
Exclusion criteria
* Patient has a history of basilar migraine or hemiplegic migraine * Patient does not receive migraine relief from triptan migraine treatment * Medications that may alter the pH of the stomach (acid reducing agents), such as H-2 antagonists, Proton Pump inhibitors (PPI), antacids * History of ergotamine or triptan intake greater than/equal 10 days per month on a regular basis for greater than 3 months * History of non-narcotic analgesic intake on greater then/equal 15 days per month for greater than/equal 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | Baseline, 2 hours post-dose | Pain freedom was defined as participants reporting a value of none on the four-point numeric rating scale (none=0, mild =1, moderate =2, severe =3) from baseline. Participants with baseline moderate pain or severe pain were included in the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | Baseline, 2 hours post dose | Total migraine freedom is defined as complete absence of migraine symptoms. A participant was positive for total migraine freedom at a particular time point if he/she reports the absence of: pain, nausea, photophobia, and phonophobia. This corresponds to reporting none on each of the four-point numeric rating scale (none =0, mild =1, moderate =2, severe =3) from baseline associated with these symptoms. Participants with baseline moderate pain or severe pain were included in the analysis. |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | AEs: from first dose to end of treatment visit (up to 7 weeks); SAE: from signing of informed consent to 30 days after the last dose (up to 11 weeks). | An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. |
| Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | 2 hours to 24 hours post dose | Participants were considered to have sustained pain freedom if all of their reported pain readings in the interval are none on the four point numeric rating scale (no pain=0, mild pain=1, moderate pain=2, severe pain=3). The intervals are inclusive of the endpoints. Sustained pain freedom was analyzed with a Cochran Mantel Haenszel (CMH) test for general association that compares the ED90 to placebo, and controls for baseline pain severity. |
| Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | 2 hours to 48 hours post dose | Participants were considered to have sustained pain freedom if all of their reported pain readings in the interval are none on the four point numeric rating scale (no pain=0, mild pain=1, moderate pain=2, severe pain=3). The intervals are inclusive of the endpoints. Sustained pain freedom was analyzed with a CMH test for general association that compares the ED90 to placebo, and controls for baseline pain severity. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 41 centers in the United States. A total of 1026 participants were enrolled in the study, and 885 of these were randomized to treatment. Of the 141 participants who were not randomized, the main reason for non-randomization was participants no longer met inclusion criteria.
Pre-assignment details
The study was divided into 3 phases: a screening/baseline phase (3-28 days), an acute treatment phase (up to 45 days during which participants were treated on 1 migraine headache of moderate to severe intensity), followed by an end-of-treatment visit within 7 days of administration of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A: Rimegepant, 10 mg Participants received a single dose (one capsule) of rimegepant 10 mg orally and three rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | 85 |
| Treatment B: Rimegepant, 25 mg Participants received a single dose (one capsule) of rimegepant 25 mg orally, and three rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | 68 |
| Treatment C: Rimegepant, 75 mg Participants received a single dose (one capsule) of rimegepant 75 mg orally, and three rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | 91 |
| Treatment D: Rimegepant, 150 mg Participants received a single dose (one capsule) of rimegepant 150 mg orally, and three rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | 90 |
| Treatment E: Rimegepant, 300 mg Participants received a single dose (two 150 mg capsules) of rimegepant 300 mg orally; and two rimegepant placebo-matching capsules, orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | 121 |
| Treatment F: Rimegepant, 600 mg Participants received a single dose (four capsules of 150 mg each) of rimegepant 600 mg orally, anytime within 45 days of randomization, once they experienced a migraine headache of moderate to severe intensity. | 92 |
| Treatment P: Rimegepant Placebo-Matching Capsules Participants received a single dose (4 capsules) of rimegepant placebo-matching capsules orally, anytime within 45 days of randomization once they experienced a migraine headache of moderate to severe intensity. | 229 |
| Treatment G: Sumatriptan 100 mg Participants received a single dose (one capsule) of rimegepant-matching sumatriptan 100 mg orally and three matching placebo capsules orally, anytime within 45 days of randomization once they experienced a migraine headache of moderate to severe intensity. | 109 |
| Total | 885 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 2 | 2 | 1 | 5 | 1 |
| Overall Study | Patient No Longer Meets Study Criteria | 7 | 6 | 3 | 2 | 5 | 5 | 9 | 6 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Subject Withdrew Consent | 3 | 0 | 1 | 0 | 2 | 1 | 5 | 2 |
Baseline characteristics
| Characteristic | Treatment A: Rimegepant, 10 mg | Treatment B: Rimegepant, 25 mg | Treatment C: Rimegepant, 75 mg | Treatment D: Rimegepant, 150 mg | Treatment E: Rimegepant, 300 mg | Treatment F: Rimegepant, 600 mg | Treatment P: Rimegepant Placebo-Matching Capsules | Treatment G: Sumatriptan 100 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 41.1 years STANDARD_DEVIATION 10.36 | 36.5 years STANDARD_DEVIATION 11.92 | 38.5 years STANDARD_DEVIATION 11.87 | 39.2 years STANDARD_DEVIATION 11.26 | 41.9 years STANDARD_DEVIATION 11.46 | 39.3 years STANDARD_DEVIATION 13.01 | 37.9 years STANDARD_DEVIATION 11.36 | 40.6 years STANDARD_DEVIATION 10.47 | 39.3 years STANDARD_DEVIATION 11.52 |
| Sex: Female, Male Female | 67 Participants | 61 Participants | 81 Participants | 63 Participants | 101 Participants | 76 Participants | 196 Participants | 91 Participants | 736 Participants |
| Sex: Female, Male Male | 18 Participants | 7 Participants | 10 Participants | 27 Participants | 20 Participants | 16 Participants | 33 Participants | 18 Participants | 149 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 / 85 | 0 / 68 | 0 / 91 | 0 / 90 | 0 / 121 | 0 / 92 | 0 / 229 | 0 / 109 |
| other Total, other adverse events | 4 / 72 | 0 / 62 | 3 / 86 | 3 / 86 | 6 / 112 | 7 / 84 | 5 / 209 | 2 / 100 |
| serious Total, serious adverse events | 0 / 72 | 0 / 62 | 0 / 86 | 3 / 86 | 0 / 112 | 0 / 84 | 0 / 209 | 0 / 100 |
Outcome results
Primary
Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose
Pain freedom was defined as participants reporting a value of none on the four-point numeric rating scale (none=0, mild =1, moderate =2, severe =3) from baseline. Participants with baseline moderate pain or severe pain were included in the analysis.
Time frame: Baseline, 2 hours post-dose
Population: Efficacy population - all participants who took study medication with 1 post-randomization efficacy evaluation and a corresponding baseline pain evaluation for the treated headache. Participants with mild baseline pain are excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: Rimegepant, 10 mg | Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | 14 Participants |
| Treatment B: Rimegepant, 25 mg | Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | 12 Participants |
| Treatment C: Rimegepant, 75 mg | Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | 27 Participants |
| Treatment D: Rimegepant, 150 mg | Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | 28 Participants |
| Treatment E: Rimegepant, 300 mg | Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | 33 Participants |
| Treatment F: Rimegepant, 600 mg | Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | 20 Participants |
| Treatment P: Rimegepant Placebo-Matching Capsules | Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | 31 Participants |
| Treatment G: Sumatriptan 100 mg | Number of Pain Free Participants (Pain Freedom) at 2 Hours Post-dose | 35 Participants |
Secondary
Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose
Participants were considered to have sustained pain freedom if all of their reported pain readings in the interval are none on the four point numeric rating scale (no pain=0, mild pain=1, moderate pain=2, severe pain=3). The intervals are inclusive of the endpoints. Sustained pain freedom was analyzed with a Cochran Mantel Haenszel (CMH) test for general association that compares the ED90 to placebo, and controls for baseline pain severity.
Time frame: 2 hours to 24 hours post dose
Population: Efficacy population - all participants who took study medication with 1 post-randomization efficacy evaluation and a corresponding baseline pain evaluation for the treated headache. Participants with Mild baseline pain are excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: Rimegepant, 10 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | 9 Participants |
| Treatment B: Rimegepant, 25 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | 10 Participants |
| Treatment C: Rimegepant, 75 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | 24 Participants |
| Treatment D: Rimegepant, 150 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | 24 Participants |
| Treatment E: Rimegepant, 300 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | 29 Participants |
| Treatment F: Rimegepant, 600 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | 17 Participants |
| Treatment P: Rimegepant Placebo-Matching Capsules | Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | 15 Participants |
| Treatment G: Sumatriptan 100 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 24 Hours Post Dose | 26 Participants |
Secondary
Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose
Participants were considered to have sustained pain freedom if all of their reported pain readings in the interval are none on the four point numeric rating scale (no pain=0, mild pain=1, moderate pain=2, severe pain=3). The intervals are inclusive of the endpoints. Sustained pain freedom was analyzed with a CMH test for general association that compares the ED90 to placebo, and controls for baseline pain severity.
Time frame: 2 hours to 48 hours post dose
Population: Efficacy population - all participants who took study medication with 1 post-randomization efficacy evaluation and a corresponding baseline pain evaluation for the treated headache. Participants with Mild baseline pain are excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: Rimegepant, 10 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | 8 Participants |
| Treatment B: Rimegepant, 25 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | 9 Participants |
| Treatment C: Rimegepant, 75 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | 24 Participants |
| Treatment D: Rimegepant, 150 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | 24 Participants |
| Treatment E: Rimegepant, 300 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | 29 Participants |
| Treatment F: Rimegepant, 600 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | 17 Participants |
| Treatment P: Rimegepant Placebo-Matching Capsules | Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | 15 Participants |
| Treatment G: Sumatriptan 100 mg | Number of Participants Achieving Sustained Pain Freedom From 2 to 48 Hours Post Dose | 26 Participants |
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition, unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or suspected transmission of an infectious agent, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes.
Time frame: AEs: from first dose to end of treatment visit (up to 7 weeks); SAE: from signing of informed consent to 30 days after the last dose (up to 11 weeks).
Population: The analysis was performed on safety population, defined as all participants in the randomized population who took at least 1 capsule of study medication, as identified on the dosing record.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Rimegepant, 10 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | AEs | 15 Participants |
| Treatment A: Rimegepant, 10 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | Participants discontinued due to AEs | 0 Participants |
| Treatment A: Rimegepant, 10 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | SAEs | 0 Participants |
| Treatment B: Rimegepant, 25 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | Participants discontinued due to AEs | 0 Participants |
| Treatment B: Rimegepant, 25 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | SAEs | 0 Participants |
| Treatment B: Rimegepant, 25 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | AEs | 10 Participants |
| Treatment C: Rimegepant, 75 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | Participants discontinued due to AEs | 0 Participants |
| Treatment C: Rimegepant, 75 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | AEs | 18 Participants |
| Treatment C: Rimegepant, 75 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | SAEs | 0 Participants |
| Treatment D: Rimegepant, 150 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | AEs | 12 Participants |
| Treatment D: Rimegepant, 150 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | SAEs | 3 Participants |
| Treatment D: Rimegepant, 150 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | Participants discontinued due to AEs | 0 Participants |
| Treatment E: Rimegepant, 300 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | SAEs | 0 Participants |
| Treatment E: Rimegepant, 300 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | AEs | 18 Participants |
| Treatment E: Rimegepant, 300 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | Participants discontinued due to AEs | 0 Participants |
| Treatment F: Rimegepant, 600 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | SAEs | 0 Participants |
| Treatment F: Rimegepant, 600 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | AEs | 14 Participants |
| Treatment F: Rimegepant, 600 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | Participants discontinued due to AEs | 0 Participants |
| Treatment P: Rimegepant Placebo-Matching Capsules | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | SAEs | 0 Participants |
| Treatment P: Rimegepant Placebo-Matching Capsules | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | AEs | 29 Participants |
| Treatment P: Rimegepant Placebo-Matching Capsules | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | Participants discontinued due to AEs | 0 Participants |
| Treatment G: Sumatriptan 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | AEs | 17 Participants |
| Treatment G: Sumatriptan 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | SAEs | 0 Participants |
| Treatment G: Sumatriptan 100 mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuation Due to Adverse Events | Participants discontinued due to AEs | 0 Participants |
Secondary
Number of Participants With Total Migraine Freedom at 2 Hours Post Dose
Total migraine freedom is defined as complete absence of migraine symptoms. A participant was positive for total migraine freedom at a particular time point if he/she reports the absence of: pain, nausea, photophobia, and phonophobia. This corresponds to reporting none on each of the four-point numeric rating scale (none =0, mild =1, moderate =2, severe =3) from baseline associated with these symptoms. Participants with baseline moderate pain or severe pain were included in the analysis.
Time frame: Baseline, 2 hours post dose
Population: Efficacy population - all participants who took study medication with 1 post-randomization efficacy evaluation and a corresponding baseline pain evaluation for the treated headache. Participants with Mild baseline pain are excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: Rimegepant, 10 mg | Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | 13 Participants |
| Treatment B: Rimegepant, 25 mg | Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | 11 Participants |
| Treatment C: Rimegepant, 75 mg | Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | 24 Participants |
| Treatment D: Rimegepant, 150 mg | Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | 22 Participants |
| Treatment E: Rimegepant, 300 mg | Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | 26 Participants |
| Treatment F: Rimegepant, 600 mg | Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | 16 Participants |
| Treatment P: Rimegepant Placebo-Matching Capsules | Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | 24 Participants |
| Treatment G: Sumatriptan 100 mg | Number of Participants With Total Migraine Freedom at 2 Hours Post Dose | 32 Participants |