Migraine, With or Without Aura
Conditions
Brief summary
The purpose of this study is to compare the efficacy of BHV-3000 (rimegepant) versus placebo in subjects with Acute Migraines
Interventions
DRUGRimegepant
75 mg tablet QD
DRUGPlacebo
Placebo tablet to match rimegepant dose QD
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind to Sponsor, Investigator and Participant
Intervention model description
Randomized Controlled Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Patient has at least 1 year history of migraines (with or without aura), consistent with a diagnosis according to the International Classification of Headache Disorder, 3rd Edition, Beta version\[1\] including the following: * Not more than 8 attacks of moderate or severe intensity per month within last 3 months * Consistent migraine headaches of at least 2 migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening Period 2. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and maintains this requirement during the Screening Period 3. Patients on prophylactic migraine medication are permitted to remain on therapy provided they have been on a stable dose for at least 3 months prior to study entry. 4. Patients with contraindications for use of triptans may be included provided they meet all other study entry criteria. Key
Exclusion criteria
1. Patient history of HIV disease 2. Patient history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Patients with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS),Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening. 3. Uncontrolled hypertension (high blood pressure), or uncontrolled diabetes (however patients can be included who have stable hypertension and/or diabetes for 3 months prior to being enrolled) 4. Patient has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (eg, schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments 5. Patient has a history of gastric, or small intestinal surgery, or has a disease that causes mal-absorption 6. The patient has a history or current evidence of any significant and/or unstable medical conditions (eg, history of congenital heart disease or arrhythmia, known suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial 7. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or patients who have met DSM-V criteria for any significant substance use disorder within the past 12 months from the date of the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Freedom From Pain at 2 Hours Post-dose | 2 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic diary (eDiary). Pain freedom was defined as pain level of none. |
| Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose | 2 hours post-dose | MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at onset that was absent post-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pain Relief at 2 Hours Post-dose | 2 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild. |
| Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose | 2 hours post-dose | Nausea status was measured as absent or present in the eDiary. Freedom from nausea was defined as nausea absent. |
| Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose | 24 hours post-dose | Participants who did not experience relief of their migraine headache at the end of 2 hours after dosing with study medication (and after the 2-hour assessments had been completed on the eDiary) were permitted to use the following rescue medications: aspirin, ibuprofen, acetaminophen up to 1000 mg/day (this includes Excedrin Migraine), naproxen (or any other type of nonsteroidal anti-inflammatory drug), antiemetics (e.g., metoclopramide or promethazine), or baclofen. The participant's use of rescue medication was recorded by the participant in a paper diary. |
| Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose | From 2 hours up to 24 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose. |
| Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose | 2 hours post-dose | Photophobia (sensitivity to light) status was measured as absent or present in the eDiary. Freedom from photophobia was defined as photophobia absent. |
| Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose | From 2 hours up to 48 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose. |
| Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose | From 2 hours up to 48 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose. |
| Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose | From 2 hours up to 48 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relapse was defined as pain level of mild, moderate, or severe after 2 hours up to 48 hours for the participants who were pain-free at 2 hours post-dose. |
| Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose | 2 hours post-dose | Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function. |
| Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose | From 2 hours up to 24 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose. |
| Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose | 2 hours post-dose | Phonophobia (sensitivity to sound) status was measured as absent or present in the eDiary. Freedom from phonophobia was defined as phonophobia absent. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 50 centers in the United States.
Pre-assignment details
A total of 1485 participants were enrolled, of which 1162 participants were randomized to BHV-3000 (rimegepant) 75 milligram (mg) or placebo. A total of 323 participants failed screening mainly due to failure to meet eligibility criteria.The randomization was stratified in a 1:1 ratio based on use of prophylactic migraine medications (yes or no).
Participants by arm
| Arm | Count |
|---|---|
| Rimegepant 75 mg Participants were administered a single oral dose of 75 mg of rimegepant on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization. | 543 |
| Placebo Participants were administered a single oral dose of matching placebo for rimegepant (75 mg) on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization. | 541 |
| Total | 1,084 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 11 |
| Overall Study | Not Experienced Moderate/Severe Migraine | 23 | 17 |
| Overall Study | Other Reasons | 3 | 5 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Deviation | 1 | 3 |
| Overall Study | Technical Problems | 3 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Rimegepant 75 mg | Placebo |
|---|---|---|---|
| Age, Continuous | 41.636 years STANDARD_DEVIATION 12.2322 | 41.945 years STANDARD_DEVIATION 12.3286 | 41.326 years STANDARD_DEVIATION 12.1381 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 126 Participants | 58 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 958 Participants | 485 Participants | 473 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Primary Migraine Type Migraine with Aura | 373 Participants | 190 Participants | 183 Participants |
| Primary Migraine Type Migraine without Aura | 711 Participants | 353 Participants | 358 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 6 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 187 Participants | 107 Participants | 80 Participants |
| Race (NIH/OMB) More than one race | 17 Participants | 10 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 861 Participants | 417 Participants | 444 Participants |
| Randomization Strata, Prophylactic Migraine Medication Use No | 902 Participants | 453 Participants | 449 Participants |
| Randomization Strata, Prophylactic Migraine Medication Use Yes | 182 Participants | 90 Participants | 92 Participants |
| Sex: Female, Male Female | 927 Participants | 464 Participants | 463 Participants |
| Sex: Female, Male Male | 157 Participants | 79 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 546 | 0 / 549 |
| other Total, other adverse events | 0 / 546 | 0 / 549 |
| serious Total, serious adverse events | 2 / 546 | 1 / 549 |
Outcome results
Primary
Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose
MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eDiary. Symptom status (absent, present) was assessed post-dose using the eDiary separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at onset that was absent post-dose.
Time frame: 2 hours post-dose
Population: The analysis was performed on mITT participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose | 36.6 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose | 27.7 percentage of participants |
p-value: 0.001695% CI: [3.4, 14.4]Cochran-Mantel-Haenszel
Primary
Percentage of Participants With Freedom From Pain at 2 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic diary (eDiary). Pain freedom was defined as pain level of none.
Time frame: 2 hours post-dose
Population: The analysis was performed on modified intent to treat (mITT) participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Freedom From Pain at 2 Hours Post-dose | 19.2 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Pain at 2 Hours Post-dose | 14.2 percentage of participants |
p-value: 0.029895% CI: [0.5, 9.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose
Functional disability level was assessed in the eDiary on a 4-point scale: normal function, mild impairment, severe impairment, required bed rest. Freedom from functional disability was defined as normal function.
Time frame: 2 hours post-dose
Population: The analysis was performed on mITT participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose | 33.3 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Functional Disability at 2 Hours Post-dose | 21.8 percentage of participants |
Secondary
Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose
Nausea status was measured as absent or present in the eDiary. Freedom from nausea was defined as nausea absent.
Time frame: 2 hours post-dose
Population: The analysis was performed on mITT participants with nausea present at migraine onset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose | 46.9 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose | 41.6 percentage of participants |
p-value: 0.181595% CI: [-2.4, 12.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose
Phonophobia (sensitivity to sound) status was measured as absent or present in the eDiary. Freedom from phonophobia was defined as phonophobia absent.
Time frame: 2 hours post-dose
Population: The analysis was performed on mITT participants with phonophobia present at migraine onset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose | 38.6 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose | 30.9 percentage of participants |
p-value: 0.029995% CI: [0.8, 14.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose
Photophobia (sensitivity to light) status was measured as absent or present in the eDiary. Freedom from photophobia was defined as photophobia absent.
Time frame: 2 hours post-dose
Population: The analysis was performed on mITT participants with photophobia present at migraine onset.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose | 34.9 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose | 24.8 percentage of participants |
p-value: 0.000595% CI: [4.4, 15.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relapse was defined as pain level of mild, moderate, or severe after 2 hours up to 48 hours for the participants who were pain-free at 2 hours post-dose.
Time frame: From 2 hours up to 48 hours post-dose
Population: The analysis population was performed on mITT participants with pain freedom at 2 hours post-dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose | 40.1 percentage of participants |
| Placebo | Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose | 50.0 percentage of participants |
Secondary
Percentage of Participants With Pain Relief at 2 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Pain relief was defined as pain level of none or mild.
Time frame: 2 hours post-dose
Population: The analysis was performed on mITT participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Pain Relief at 2 Hours Post-dose | 56.0 percentage of participants |
| Placebo | Percentage of Participants With Pain Relief at 2 Hours Post-dose | 45.7 percentage of participants |
p-value: 0.000695% CI: [4.4, 16.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose
Participants who did not experience relief of their migraine headache at the end of 2 hours after dosing with study medication (and after the 2-hour assessments had been completed on the eDiary) were permitted to use the following rescue medications: aspirin, ibuprofen, acetaminophen up to 1000 mg/day (this includes Excedrin Migraine), naproxen (or any other type of nonsteroidal anti-inflammatory drug), antiemetics (e.g., metoclopramide or promethazine), or baclofen. The participant's use of rescue medication was recorded by the participant in a paper diary.
Time frame: 24 hours post-dose
Population: The analysis was performed on mITT participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose | 20.4 percentage of participants |
| Placebo | Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose | 31.8 percentage of participants |
Secondary
Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.
Time frame: From 2 hours up to 24 hours post-dose
Population: The analysis was performed on mITT participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose | 14.0 percentage of participants |
| Placebo | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose | 8.1 percentage of participants |
Secondary
Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.
Time frame: From 2 hours up to 48 hours post-dose
Population: The analysis was performed on mITT participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose | 11.6 percentage of participants |
| Placebo | Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose | 7.2 percentage of participants |
Secondary
Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose.
Time frame: From 2 hours up to 24 hours post-dose
Population: The analysis was performed on mITT participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose | 38.9 percentage of participants |
| Placebo | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose | 27.9 percentage of participants |
Secondary
Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eDiary. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose.
Time frame: From 2 hours up to 48 hours post-dose
Population: The analysis was performed on mITT participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose | 33.7 percentage of participants |
| Placebo | Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose | 23.9 percentage of participants |