Acute Treatment Trial in Adult Subjects With Migraines

Phase II/III: Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Trial of BHV-3500 for the Acute Treatment of Migraine

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.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Zavegepant; Device: Intranasal Aptar Pharma Unit Dose System; Drug: Zavegepant matching placebo

• Study Type: Interventional
• Enrollment (Actual): 2154
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc.
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center For Clinical Research
  • California
    • Encino, California, United States, 91316
      • Pharmacology Research Institute
    • La Mesa, California, United States, 91942
      • eStudySite
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, LLC
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Institute
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • Panorama City, California, United States, 91402
      • National Research Institute
    • San Francisco, California, United States, 94102
      • Optimus Medical Group
    • Santa Monica, California, United States, 90404
      • Neurological Research Institute
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Colorado
    • Denver, Colorado, United States, 80210
      • Denver Neurological Research, LLC
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • CT Clinical Research
    • Stamford, Connecticut, United States, 06905
      • Ki Health Partners, LLc, dba New England Institute for Clinical Research
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Lake City, Florida, United States, 32055
      • Multi-Specialty Research Associates, Inc.
    • Miami, Florida, United States, 33143
      • Qps Mra, Llc
    • Miami, Florida, United States, 33012
      • Aga Clinical Trials
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
    • Ormond Beach, Florida, United States, 32174
      • Ormond Medical Arts Pharmaceutical Research Center
    • Tampa, Florida, United States, 33634
      • Meridien Research
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta, LLC
    • Savannah, Georgia, United States, 31405
      • Meridian Clinical Research
  • Illinois
    • Wauconda, Illinois, United States, 60084
      • Family Medicine Specialists/CIS
  • Kansas
    • Prairie Village, Kansas, United States, 66208
      • Phoenix Medical Research
  • Louisiana
    • Chalmette, Louisiana, United States, 70043
      • Crescent City Headache and Neurology Center, LLC
    • New Orleans, Louisiana, United States, 70119
      • New Orleans Center for Clinical Research
    • New Orleans, Louisiana, United States, 70124
      • DelRicht Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Marlborough, Massachusetts, United States, 01752
      • Community Clinical Research Network
    • North Attleboro, Massachusetts, United States, 02169
      • Regeneris Medical
    • Watertown, Massachusetts, United States, 02472
      • MedVadis Research Corporation
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head Pain & Neurological Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute, Inc.
    • Plymouth, Minnesota, United States, 55441
      • Clinical Research Institute, Inc.
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • MedPharmics, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Center for Pharmaceutical Research, LLC
    • North Kansas City, Missouri, United States, 64116
      • Meritas Health Neurology
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research, LLC
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
    • Springfield, Missouri, United States, 65810
      • Clinvest Research LLC
    • Springfield, Missouri, United States, 65802
      • QPS Bio-Kinetic Clinical Applications, LLC
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center: Headache Center
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates, LLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • PMG Research of Charlotte, LLC
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center
    • Raleigh, North Carolina, United States, 27609
      • PMG Research of Raleigh, LLC
    • Wilmington, North Carolina, United States, 28401
      • Wilmington Health, PLLC
  • Ohio
    • Cincinnati, Ohio, United States, 45215
      • Hometown Urgent Care and Research
    • Columbus, Ohio, United States, 43214
      • Hometown Urgent Care and Research
    • Dayton, Ohio, United States, 45424
      • Hometown Urgent Care and Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73134
      • Hightower Clinical
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network (Oregon) Inc.
    • Salem, Oregon, United States, 97301
      • Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
      • Meridian Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research/New Orleans Center for Clinical Research/Volunteer Research
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions dba CNS Healthcare
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc.
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas
    • Fort Worth, Texas, United States, 76104
      • Ventavia Research Group
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Lake Jackson, Texas, United States, 77566
      • Red Star Research, LLC
    • Magnolia, Texas, United States, 77355
      • Advanced Pharmaceutical Development Clinical Research
    • San Antonio, Texas, United States, 78230
      • Victorium Clinical Research
    • Tomball, Texas, United States, 77375
      • Dynamed Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research, LLC
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center, LLC
    • Virginia Beach, Virginia, United States, 23454
      • Tidewater Integrated Medical Research
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53144
      • Clinical Investigation Specialists, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zavegepant 5 mg; Participants administered a single intranasal dose of zavegepant 5 mg on occurrence of migraine that reached moderate or severe intensity within 45 days after randomization. The dose was administered using Aptar Unidose System (UDS) liquid spray device.	Drug: Zavegepant; A single dose of zavegepant; Other Names: BHV3500; Device: Intranasal Aptar Pharma Unit Dose System; A single-dose intranasal device
Experimental: Zavegepant 10 mg; Participants administered a single intranasal dose of zavegepant 10 mg on occurrence of migraine that reached moderate or severe intensity within 45 days after randomization. The dose was administered using Aptar UDS liquid spray device.	Drug: Zavegepant; A single dose of zavegepant; Other Names: BHV3500; Device: Intranasal Aptar Pharma Unit Dose System; A single-dose intranasal device
Experimental: Zavegepant 20 mg; Participants administered a single intranasal dose of zavegepant 20 mg on occurrence of migraine that reached moderate or severe intensity within 45 days after randomization. The dose was administered using Aptar UDS liquid spray device.	Drug: Zavegepant; A single dose of zavegepant; Other Names: BHV3500; Device: Intranasal Aptar Pharma Unit Dose System; A single-dose intranasal device
Placebo Comparator: Placebo; Participants administered a single intranasal dose of zavegepant-matching placebo on occurrence of migraine that reached moderate or severe intensity within 45 days after randomization. The dose was administered using Aptar UDS liquid spray device.	Device: Intranasal Aptar Pharma Unit Dose System; A single-dose intranasal device; Drug: Zavegepant matching placebo; A single dose of placebo matched to zavegepant

What is the study measuring?

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 clinical outcome assessment (eCOA) handheld device. Pain freedom was defined as pain level of none post-dose.	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 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.	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 eCOA handheld device. Pain relief was defined as pain level of none or mild.	2 hours post-dose
Percentage of Participants Who Were Able to Function Normally at 2 Hours Post-dose	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.	2 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 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.	Through 24 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 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.	2 hours 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 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.	2 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 eCOA handheld device. Pain relief was defined as pain level of none or mild.	60 minutes post-dose
Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose	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.	60 minutes post-dose
Percentage of Participants With Pain Relief at 30 Minutes Post-dose	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.	30 minutes post-dose
Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose	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.	30 minutes 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 eCOA handheld device. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose.	From 2 hours up to 24 hours 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 eCOA handheld device. Sustained pain freedom was defined as pain level of none at 2 hours up to 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 eCOA handheld device. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose.	From 2 hours up to 48 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 eCOA handheld device. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose.	From 2 hours up to 48 hours post-dose
Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose	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.	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 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.	From 2 hours up to 48 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): November 11, 2019

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: nausea; photophobia; Acute Migraine; phonophobia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: BHV3500-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes