Trial in Adult Subjects With Acute Migraines

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of BHV-3000 (rimegepant ODT) versus placebo in subjects with Acute Migraines.

Official Title
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BHV3000-303: Phase 3, Double-Blind, Randomized, Placebo Controlled, Safety and Efficacy Trial of BHV-3000 (Rimegepant) Orally Disintegrating Tablet (ODT) for the Acute Treatment of Migraine

Conditions
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Migraine, With or Without Aura

Intervention / Treatment
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* Drug: Rimegepant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 1. Subject 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: 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 Not more than 8 attacks of moderate to severe intensity per month within the 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 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. Subjects 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 screening visit and the dose is not expected to change during the course of the study. Subjects with contraindications for use of triptans may be included provided they meet all other study entry criteria. Key Exclusion Criteria: Subject with a history of HIV disease Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. subjects 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 Uncontrolled hypertension (high blood pressure), or uncontrolled diabetes (however subjects can be included who have stable hypertension and/or diabetes for at least 3 months prior to being enrolled) Subject has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (e.g., schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion might interfere with study assessments. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease that causes malabsorption The subject has a history of current or evidence of any significant and/ or unstable medical conditions (e.g., 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. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or subjects who have met DSM-V criteria for any significant substance use disorder within the past 12 months from the date of the screening visit. Subjects are excluded if they have previously participated in any BHV-30000 (rimegepant) study within the last 2 years. Participation in any other investigational clinical trial while participating in this clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Controlled Trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Rimegepant 75 mg<br>Participants were administered a single sublingual dose of 75 mg of rimegepant ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization. | Drug: Rimegepant<br>* 75 mg ODT QD<br>* Other names: BHV-3000;|
| Placebo Comparator: Arm 2: Placebo<br>Participants were administered a single sublingual dose of matching placebo for rimegepant (75 mg) ODT on occurrence of migraine that reached moderate or severe intensity up to 45 days after randomization. | Drug: Placebo<br>* Placebo ODT to match rimegepant dose QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 hours post-dose | 
| 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. | 2 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 hours post-dose | 
| 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. | 2 hours post-dose | 
| 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. | From 2 hours up to 24 hours post-dose | 
| Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 24 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. Sustained freedom was defined as MBS reported at onset that was absent at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose. | From 2 hours up to 24 hours post-dose | 
| 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. | 24 hours post-dose | 
| Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 24 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. Sustained freedom from functional disability was defined as normal function at 2 hours up to 24 hours post-dose with no rescue medication use through 24 hours post-dose. | From 2 hours up to 24 hours post-dose | 
| 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. | From 2 hours up to 48 hours post-dose | 
| Percentage of Participants With Sustained Freedom From Most Bothersome Symptom (MBS) From 2 to 48 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. Sustained freedom was defined as MBS reported at onset that was absent at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose. | From 2 hours up to 48 hours post-dose | 
| Percentage of Participants With Sustained Freedom From Functional Disability From 2 to 48 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. Sustained freedom from functional disability was defined as normal function at 2 hours up to 48 hours post-dose with no rescue medication use through 48 hours post-dose. | From 2 hours up to 48 hours post-dose | 
| 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. | 2 hours post-dose | 
| Percentage of Participants With Freedom From Functional Disability at 90 Minutes 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. | 90 minutes post-dose | 
| Percentage of Participants With Pain Relief at 90 Minutes 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. | 90 minutes post-dose | 
| 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. | From 2 hours up to 24 hours post-dose | 
| Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 90 Minutes 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. | 90 minutes post dose | 
| Percentage of Participants With Freedom From Pain at 90 Minutes 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. | 90 minutes post-dose | 
| 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. | 2 hours post-dose | 
| 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. | From 2 hours up to 48 hours post-dose | 
| Percentage of Participants With Pain Relief at 60 Minutes 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. | 60 minutes post-dose | 
| Percentage of Participants With Freedom From Functional Disability at 60 Minutes 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. | 60 minutes post-dose | 
| 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. | 2 hours post-dose | 
| 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 post-dose for the participants who were pain-free at 2 hours post-dose. | From 2 hours up to 48 hours post-dose |