Randomized Trial in Adult Participants With Acute Migraines

Double-Blind, Randomized, Placebo-controlled, Safety and Efficacy Trial of BHV-3500 (Zavegepant) Intranasal for the Acute Treatment of Migraine

The purpose of this study is to test the safety and efficacy of BHV-3500 (zavegepant) versus placebo in the acute treatment of moderate or severe migraine.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Placebo; Drug: Zavegepant

• Study Type: Interventional
• Enrollment (Actual): 1978
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Medical Affiliated Research Center
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, LLC, An AMR Co.
  • Arizona
    • Chandler, Arizona, United States, 85286
      • MD First Research
    • Tucson, Arizona, United States, 85710
      • Tucson Neuroscience Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research
  • California
    • Colton, California, United States, 92324
      • Axiom Research, Llc
    • 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
    • Los Angeles, California, United States, 90404
      • Clinical Research Institute
    • Newport Beach, California, United States, 92660
      • Wr-Pri, Llc
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, inc.
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • CT Clinical Research
    • Stamford, Connecticut, United States, 06095
      • Ki Health Partners, LLC dba New England Institute for Clinical Research
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Neurology Offices of South Florida
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Lake City, Florida, United States, 32055
      • Multi-Specialty Research Associates, Inc.
    • Lake Mary, Florida, United States, 32746
      • Meridien Research
    • Miami, Florida, United States, 33155
      • AppleMed Research Group, LLC
    • Miami, Florida, United States, 33176
      • The Neurology Research Group
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
    • Orlando, Florida, United States, 32819
      • Clinical Neuroscience Solutions, Inc.
    • Ormond Beach, Florida, United States, 32174
      • Complete Health Research
    • Pembroke Pines, Florida, United States, 33026
      • Ideal Clinical Research
    • Pompano Beach, Florida, United States, 33060
      • Clinical Research Center of Florida
    • South Miami, Florida, United States, 33143
      • Clin-Med Research & Development, LLC
    • Tampa, Florida, United States, 33613
      • ForCare Clinical Research
    • Tampa, Florida, United States, 33634
      • JSV Clinical Research Study, Inc.
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta, LLC
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research, LLC
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials Inc.
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • Flossmoor, Illinois, United States, 60422
      • Healthcare Research Network II, LLC
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Neurological Center
  • Kansas
    • Prairie Village, Kansas, United States, 66208
      • Collective Medical Research
    • Wichita, Kansas, United States, 67205
      • Alliance for Multispecialty Research, LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Louisiana
    • Chalmette, Louisiana, United States, 70043
      • Crescent City Headache and Neurology Center
    • 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
    • South Dartmouth, Massachusetts, United States, 02747
      • Boston Neuro Research Center
    • Waltham, Massachusetts, United States, 02451
      • MedVadis Research Corporation
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Headache and Neurological Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute, Inc.
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Healthcare Research Network
    • 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
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
  • 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
    • Endwell, New York, United States, 13760
      • Regional Clinical Research
    • Manlius, New York, United States, 13104
      • Central New York Clinical Research
    • New York, New York, United States, 10017
      • Fieve Clinical Research, Inc
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest LLC
    • Raleigh, North Carolina, United States, 27609
      • PMG of Raleigh, LLC
    • Wilmington, North Carolina, United States, 28401
      • Wilmington Health, PLLC
  • Ohio
    • Cincinnati, Ohio, United States, 45215
      • Hometown Urgent Care & Research/ Wellnow
    • Columbus, Ohio, United States, 43214
      • Hometown Urgent Care and Research
    • Dayton, Ohio, United States, 45424
      • Hometown Urgent Care and Research
    • New Albany, Ohio, United States, 43054
      • The Orthopedic Foundation
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • OK Clinical Research LLC
    • Yukon, Oklahoma, United States, 73099
      • Tekton Research, Inc.
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research of Philadelphia, LLC
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians, Inc.
    • Union, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians, Inc.
  • South Carolina
    • Lancaster, South Carolina, United States, 29720
      • MD First Research
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Austin, Texas, United States, 78737
      • Donald J. Garcia, Jr, MD, PA
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Lake Jackson, Texas, United States, 77566
      • Red Star Research LLC
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc. (CTT)
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Alpine Medical Group
    • South Jordan, Utah, United States, 84095
      • J. Lewis Research, Inc. / Jordan River Family Medicine
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center, LLC
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.
    • Virginia Beach, Virginia, United States, 23454
      • Tidewater Integrated Medical Research
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98105
      • Seattle Women's: Health, Research, Gynecology
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53144
      • Clinical Investigation Specialist, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant 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, 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 maintains this requirement during 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 maintains this requirement during 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.
2. Male and Female participants ≥18 years of age.

Exclusion Criteria:

1. Participant with a history of HIV disease
2. 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 (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 participants can be included who have stable hypertension and/or diabetes for at least 3 months prior to being enrolled).
4. Participants with major depressive episode within the last 12 months, major depressive disorder or any anxiety disorder requiring more than 1 medication for each disorder.
5. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or participants who have met DSM-V criteria for any significant substance use disorder within the past 12 months.
6. History of nasal surgery in the 6 months.
7. Evidence at screening of significant nasal conditions that may affect the administration or absorption of the nasal product (e.g. severe septum deviation, nasal deformity or blockage, inflammation, perforation, mucosal erosion or ulceration, polyposis, nasal trauma)
8. Participation in any other investigational clinical trial while participating in this clinical trial. Participation in a COVID-19 mRNA vaccine study (vaccine must be authorized under FDA emergency use authorization or approval) who are at least 30 days post last dose of the vaccine are permitted to be screened for this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zavegepant; Participants administered a single intranasal dose of zavegepant 10 mg on occurrence of migraine with moderate or severe intensity within 45 days after randomization. The dose was administered using an Aptar Unidose System (UDS) liquid spray device.	Drug: Zavegepant; One dose of zavegepant; Other Names: BHV3500
Placebo Comparator: Placebo; Participants administered a single intranasal dose of zavegepant matching placebo on occurrence of migraine with moderate or severe intensity within 45 days after randomization. The dose was administered using an Aptar UDS liquid spray device.	Drug: Placebo; One dose of matching placebo

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 immediately before dosing 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 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 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 2 Hours Post-dose	Functional disability 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 Sustained Pain Relief From 2 Hours to 24 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 to 24 hours post-dose
Percentage of Participants With Sustained Pain Relief From 2 Hours to 48 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 to 48 hours post-dose
Percentage of Participants With Sustained Pain Freedom From 2 Hours to 24 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 to 24 hours post-dose
Percentage of Participants With Sustained Pain Freedom From 2 Hours to 48 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 to 48 hours post-dose
Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose	Functional disability 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) present at on-study migraine attack onset.	60 minutes post-dose
Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose	Functional disability 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 Pain Relief at 15 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.	15 minutes post-dose
Percentage of Participants Who Were Able to Function Normally at 15 Minutes Post-dose	Functional disability 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.	15 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 eCOA handheld device. Freedom from nausea was defined as nausea absent post-dose 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 to 48 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2020
• Primary Completion (Actual): October 10, 2021
• Study Completion (Actual): October 22, 2021

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): September 30, 2020

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Nausea; Photophobia; Phonophobia; Acute Migraine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: BHV3500-301; C5301001 (Other Identifier: Pfizer)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No