Brief Summary
The purpose of the study is to evaluate the safety and efficacy of three different intranasal dose levels of zavegepant (BHV-3500), relative to placebo, in the acute treatment of moderate to severe migraine.
Brief Title
Acute Treatment Trial in Adult Subjects With Migraines
Categories
Completion Date
Completion Date Type
Actual
Conditions
Migraine
Eligibility Criteria
Inclusion Criteria:
Key Inclusion Criteria:
1. Participants have 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, including the following:
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. Not more than 8 attacks of moderate to severe intensity per month within the last 3 months.
4. At least 2 consistent migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and throughout the Screening Period.
5. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and throughout the Screening Period.
6. Participants 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.
7. Participants with contraindications for use of triptans may be included provided they meet all other study entry criteria.
Exclusion Criteria:
Key Exclusion Criteria:
1. Participant with a history of basilar migraine or hemiplegic migraine.
2. Participant with a history of human immunodeficiency virus (HIV) disease.
3. Participant history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Participants with myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke or transient ischemic attack during the 6 months prior to screening.
4. 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).
5. Participant has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (for example, schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion might interfere with study assessments.
6. Participant 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.
7. The participant has a history of current or evidence of any significant and/ or unstable medical conditions (for example, 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 or interfere with assessments of safety or efficacy during the course of the trial.
8. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or subjects who have met Diagnostic and Statistical Manual of Mental Disorders Fifth edition (DSM-V) criteria for any significant substance use disorder within the past 12 months from the date of the Screening Visit.
9. History of nasal surgery in the 6 months preceding the Screening Visit.
10. Participation in any other investigational clinical trial while participating in this clinical trial.
Key Inclusion Criteria:
1. Participants have 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, including the following:
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. Not more than 8 attacks of moderate to severe intensity per month within the last 3 months.
4. At least 2 consistent migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and throughout the Screening Period.
5. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and throughout the Screening Period.
6. Participants 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.
7. Participants with contraindications for use of triptans may be included provided they meet all other study entry criteria.
Exclusion Criteria:
Key Exclusion Criteria:
1. Participant with a history of basilar migraine or hemiplegic migraine.
2. Participant with a history of human immunodeficiency virus (HIV) disease.
3. Participant history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Participants with myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke or transient ischemic attack during the 6 months prior to screening.
4. 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).
5. Participant has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (for example, schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion might interfere with study assessments.
6. Participant 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.
7. The participant has a history of current or evidence of any significant and/ or unstable medical conditions (for example, 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 or interfere with assessments of safety or efficacy during the course of the trial.
8. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or subjects who have met Diagnostic and Statistical Manual of Mental Disorders Fifth edition (DSM-V) criteria for any significant substance use disorder within the past 12 months from the date of the Screening Visit.
9. History of nasal surgery in the 6 months preceding the Screening Visit.
10. Participation in any other investigational clinical trial while participating in this clinical trial.
Inclusion Criteria
Inclusion Criteria:
Key Inclusion Criteria:
1. Participants have 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, including the following:
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. Not more than 8 attacks of moderate to severe intensity per month within the last 3 months.
4. At least 2 consistent migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and throughout the Screening Period.
5. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and throughout the Screening Period.
6. Participants 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.
7. Participants with contraindications for use of triptans may be included provided they meet all other study entry criteria.
Key Inclusion Criteria:
1. Participants have 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, including the following:
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. Not more than 8 attacks of moderate to severe intensity per month within the last 3 months.
4. At least 2 consistent migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and throughout the Screening Period.
5. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and throughout the Screening Period.
6. Participants 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.
7. Participants with contraindications for use of triptans may be included provided they meet all other study entry criteria.
Gender
All
Gender Based
false
Keywords
Acute Migraine
phonophobia
photophobia
nausea
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03872453
Org Class
Industry
Org Full Name
Pfizer
Org Study Id
BHV3500-201
Overall Status
Completed
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Phase II/III: Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Trial of BHV-3500 for the Acute Treatment of Migraine
Primary Outcomes
Outcome Description
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic clinical outcome assessment (eCOA) handheld device. Pain freedom was defined as pain level of none post-dose.
Outcome Measure
Percentage of Participants With Freedom From Pain at 2 Hours Post-dose
Outcome Time Frame
2 hours post-dose
Outcome Description
MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eCOA handheld device. Symptom status (absent, present) was assessed post-dose using the eCOA handheld device separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at on-study migraine attack onset that was absent post-dose.
Outcome Measure
Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose
Outcome Time Frame
2 hours post-dose
Secondary Outcomes
Outcome Description
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relief was defined as pain level of none or mild.
Outcome Time Frame
2 hours post-dose
Outcome Measure
Percentage of Participants With Pain Relief at 2 Hours Post-dose
Outcome Description
Functional disbaility level was assessed on a 4-point scale (normal function, mildly impaired, severely impaired, requires bedrest) using the eCOA handheld device. Normal function was defined as a functional disability level of normal post-dose in the subset of participants with functional disability (mildly impaired, severely impaired, requires bedrest) at on-study migraine attack onset.
Outcome Time Frame
2 hours post-dose
Outcome Measure
Percentage of Participants Who Were Able to Function Normally at 2 Hours Post-dose
Outcome Description
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 eCOA handheld device) 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 (for example, metoclopramide or promethazine), or baclofen. The participant's use of rescue medication was recorded by the site on a case report form.
Outcome Time Frame
Through 24 hours post-dose
Outcome Measure
Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose
Outcome Description
Photophobia (sensitivity to light) status was measured as absent or present in the eCOA handheld device. Freedom from photophobia was defined as photophobia absent post-dose in the subset of participants with photophobia present at on-study migraine attack onset.
Outcome Time Frame
2 hours post-dose
Outcome Measure
Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose
Outcome Description
Phonophobia (sensitivity to sound) status was measured as absent or present in the eCOA handheld device. Freedom from phonophobia was defined as phonophobia absent post-dose in the subset of participants with phonophobia present at on-study migraine attack onset.
Outcome Time Frame
2 hours post-dose
Outcome Measure
Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose
Outcome Description
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relief was defined as pain level of none or mild.
Outcome Time Frame
60 minutes post-dose
Outcome Measure
Percentage of Participants With Pain Relief at 60 Minutes Post-dose
Outcome Description
Functional disbaility level was assessed on a 4-point scale (normal function, mildly impaired, severely impaired, requires bedrest) using the eCOA handheld device. Normal function was defined as a functional disability level of normal post-dose in the subset of participants with functional disability (mildly impaired, severely impaired, requires bedrest) at on-study migraine attack onset.
Outcome Time Frame
60 minutes post-dose
Outcome Measure
Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose
Outcome Description
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relief was defined as pain level of none or mild.
Outcome Time Frame
30 minutes post-dose
Outcome Measure
Percentage of Participants With Pain Relief at 30 Minutes Post-dose
Outcome Description
Functional disbaility level was assessed on a 4-point scale (normal function, mildly impaired, severely impaired, requires bedrest) using the eCOA handheld device. Normal function was defined as a functional disability level of normal post-dose in the subset of participants with functional disability (mildly impaired, severely impaired, requires bedrest) at on-study migraine attack onset.
Outcome Time Frame
30 minutes post-dose
Outcome Measure
Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose
Outcome Description
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose.
Outcome Time Frame
From 2 hours up to 24 hours post-dose
Outcome Measure
Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose
Outcome Description
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain freedom was defined as pain level of none at 2 hours up to 24 hours post-dose.
Outcome Time Frame
From 2 hours up to 24 hours post-dose
Outcome Measure
Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose
Outcome Description
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose.
Outcome Time Frame
From 2 hours up to 48 hours post-dose
Outcome Measure
Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose
Outcome Description
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose.
Outcome Time Frame
From 2 hours up to 48 hours post-dose
Outcome Measure
Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose
Outcome Description
Nausea status was measured as absent or present in the eCOA handheld device. Freedom from nausea was defined as nausea absent post-odse in the subset of participants with nausea present at on-study migraine attack onset.
Outcome Time Frame
2 hours post-dose
Outcome Measure
Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose
Outcome Description
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relapse was defined as pain level of mild, moderate, or severe after 2 hours up to 48 hours post-dose in the subset of participants with pain level of none at 2 hours post-dose.
Outcome Time Frame
From 2 hours up to 48 hours post-dose
Outcome Measure
Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Cynthia E Armand
Investigator Email
carmand@montefiore.org
Investigator Phone