A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention

A Phase 2/3 Randomized, Double-Blind, Placebo- Controlled Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention

The purpose of this is study is to compare the efficacy of BHV-3500 (zavegepant) to placebo as a preventive treatment for migraine, as measured by the reduction in the number of migraine days per month.

Study Overview

• Status: Active, not recruiting
• Conditions: Migraine
• Intervention / Treatment: Drug: BHV-3500 (zavegepant); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 538
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenoscience, Inc
    • Tucson, Arizona, United States, 85710
      • Tucson Neuroscience Research
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • Colton, California, United States, 92324
      • Axiom Research, LLC
    • Encino, California, United States, 91316
      • Wr-Pri, Llc
    • La Mesa, California, United States, 91942
      • eStudySite
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research, LLC.
    • Los Angeles, California, United States, 90048
      • Clinical Research Institute
    • Newport Beach, California, United States, 92660
      • Wr-Pri, Llc
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc.
  • Connecticut
    • Hamden, Connecticut, United States, 06517
      • CMR of Greater New Haven, LLC
    • Stamford, Connecticut, United States, 06905
      • Ki Health Partners, LLc, dba New England Institute for Clinical Research
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Neurology Offices of South Florida
    • Edgewater, Florida, United States, 32132
      • Complete Health Research
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Lake City, Florida, United States, 32055
      • Multi-Specialty Research Associates, Inc.
    • Miami, Florida, United States, 33155
      • AppleMed Research Group, LLC
    • Miami, Florida, United States, 33176
      • Brainstorm Research
    • Miami, Florida, United States, 33176
      • The Neurology Research Group
    • Miami, Florida, United States, 33126
      • AppleMed Research Group, LLC
    • Orlando, Florida, United States, 32801
      • 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
    • Saint Petersburg, Florida, United States, 33709
      • Accel Research Sites Network - St. Petersburg Clinical Research Unit
    • 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
    • Decatur, Georgia, United States, 30030
      • CenExel iResearch, LLC
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • Gurnee, Illinois, United States, 60031
      • Clinical Investigation Specialists, Inc
    • Gurnee, Illinois, United States, 60031
      • Clinical Investigation Specialists, Inc.
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC.
  • Iowa
    • Sioux City, Iowa, United States, 51106
      • Meridian Clinical Research, LLC
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • Alliance for Multispecialty Reseach, LLC
    • Newton, Kansas, United States, 67114
      • Alliance for Multispecialty Research, LLC
    • Overland Park, Kansas, United States, 66211
      • Kansas Institute of Research
    • Overland Park, Kansas, United States, 66210
      • Collevtive Medical Research
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • The Research Group of Lexington, LLC
    • Lexington, Kentucky, United States, 40503
      • The Research Group of Lexington, Llc.
    • 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
    • New Orleans, Louisiana, United States, 70119
      • Alliance for Multispecialty Research, LLC.
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Foxboro, Massachusetts, United States, 02035
      • Neurology Center of New England P.C.
    • Marlborough, Massachusetts, United States, 01752
      • Community Clinical Research Network Inc
    • Waltham, Massachusetts, United States, 02451
      • MedVadis Research Corporation
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head Pain & Neurological Institute
    • Rochester, Michigan, United States, 48307
      • Romedica LLC
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispecialty Reseach, LLC
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
    • Springfield, Missouri, United States, 65810
      • Clinvest Research, LLC
    • Springfield, Missouri, United States, 65807
      • Clinvest Research, LLC
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
    • Las Vegas, Nevada, United States, 89118
      • Wr-Crcn, Llc
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center, Inc.
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • Manlius, New York, United States, 13104
      • Central New York Clinical Research
    • New York, New York, United States, 10017
      • Fieve Clinical Research, Inc
    • New York, New York, United States, 10003
      • New York Neurology Associates
    • Port Jefferson Station, New York, United States, 11776
      • North Suffolk Neurology, PC
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates, LLC
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc.
    • Raleigh, North Carolina, United States, 27609
      • Accellacare
    • Shelby, North Carolina, United States, 28150
      • Carolina Research Center, Inc.
    • Wilmington, North Carolina, United States, 28401
      • Accellacare
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
    • Cincinnati, Ohio, United States, 45215
      • Wellnow Urgent Care
    • Columbus, Ohio, United States, 43214
      • Hometown Urgent Care and Research
    • Columbus, Ohio, United States, 43214
      • Wellnow Urgent Care and Research
    • Dayton, Ohio, United States, 45424
      • Hometown Urgent Care and Research
    • Dayton, Ohio, United States, 45424
      • Wellnow Urgent Care and Research
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research, Inc.
    • Troy, Ohio, United States, 45373
      • Wellnow Urgent Care and Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73134
      • Hightower Clinical
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Headlands LLC, dba Summit Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research Philadelphia, LLC
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians, Inc.
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital Clinical Trials Office
    • West Reading, Pennsylvania, United States, 19611
      • Tower Health Medical Group - Neurology
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Internal Medicine and Pediatric Associates of Bristol, PC
    • Bristol, Tennessee, United States, 37620
      • Accellacare (Administrative Only)
    • Chattanooga, Tennessee, United States, 37421
      • WR-Clinsearch, LLC
    • Franklin, Tennessee, United States, 37067
      • KCA Neurology, PLLC
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Frisco, Texas, United States, 75034
      • North Texas Institute of Neurology and Headache
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Lake Jackson, Texas, United States, 77566
      • Red Star Research. LLC
    • Lampasas, Texas, United States, 76550
      • FMC Science
    • Lampasas, Texas, United States, 76550
      • Radiance Clinical Research
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research , LLC(Administrative Location)
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center, LLC
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.
    • Norfolk, Virginia, United States, 23502
      • Meridian Clinical Research, LLC
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98105
      • Seattle Women's: Health, Research, Gynecology
    • Seattle, Washington, United States, 98105
      • Seattle Clinical Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Subject has at least 1 year history of migraine (with or without aura) consistent with a diagnosis according to the International Classification of

Headache Disorders, 3rd Edition, including the following:

1. Age of onset of migraines prior to 50 years of age
2. Migraine attacks, on average, lasting 4 - 72 hours if untreated
3. Per subject report, at least 15 headache days per month, at lest 8 migraine days per month, and at least 1 headache-free day per month within the last 3 months prior to the Screening Visit
4. Eight or more migraine days during the Observation Period
5. 15 or more headache days during the Observation Period
6. One or more non-headache days during the Observation Period
7. Ability to distinguish migraine attacks from tension/cluster headaches
8. Subjects on prophylactic migraine medication are permitted to remain on 1 medication with possible migraine-prophylactic effects if the dose has been stable for at least 3 months prior to the Screening Visit, and the dose is not expected to change during the course of the study.

Exclusion Criteria:

1. Subject with a history of HIV disease
2. 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
3. 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 screening).
4. Subjects with major depressive episode or anxiety disorder which require more than 1 daily medication for each disorder or subjects with a major depressive episode within the last 12 months. Medications to treat major depressive disorder or an anxiety disorder must have been at a stable dose for at least 3 months prior to the Screening Visit.
5. Subjects with active chronic pain syndromes, other pain syndromes (including trigeminal neuralgia), psychiatric conditions, dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion interfere with study assessments of safety or efficacy.
6. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease or condition (e.g. chronic pancreatitis, ulcerative colitis, etc.) that causes malabsorption.
7. Body mass index > 33 kg/m2
8. History of gallstones or cholecystectomy.
9. The subject has a history or current evidence of any unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known or 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BHV-3500 200mg; Zavegepant 200mg oral soft gel capsule.	Drug: BHV-3500 (zavegepant); BHV-3500 (zavegepant) softgel capsule.
Placebo Comparator: Placebo 200mg; Matching placebo 200mg oral soft gel capsule.	Drug: Placebo; Matching placebo softgel capsule.
Active Comparator: BHV-3500 100mg; Zavegepant 100mg oral soft gel capsule.	Drug: BHV-3500 (zavegepant); BHV-3500 (zavegepant) softgel capsule.
Placebo Comparator: Placebo 100mg; Matching placebo 100mg oral soft gel capsule.	Drug: Placebo; Matching placebo softgel capsule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of zavegepant compared to placebo as a preventive treatment for migraine	Measured by the mean reduction from baseline (i.e., Observation Phase) in the number of migraine days per month over the entire Double-blind Treatment Phase.	Number of migraine during weeks 1 to 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of zavegepant compared to placebo with the number of subjects that had a ≥ 50% reduction from Observational Phase.	Measured by the number of moderate to severe migraine days per month over the entire double-blind treatment phase.	Number of migraine days during weeks 1 to 12
Efficacy of zavegepant to placebo on mean reduction from Observational Phase.	Measured by the number of migraine days in the last 4 weeks of the Double-Blind Treatment Phase.	Number of migraine days during per month during weeks 9 to 12
Efficacy of zavegepant to placebo on mean reduction from Observational Phase.	Measured by the number of migraine days per month in the first 4 weeks of the Double-Blind Treatment Phase.	Number of migraine days per month during weeks 1 to 4
Efficacy of zavegepant to placebo in the mean number of acute migraine specific medication days per month.	Measured by the number of acute migraine specific medication days over the entire Double-Blind Treatment Phase.	Number of migraine days per month during weeks 1 to 12
Mean Change From Baseline in the Migraine Specific Quality of Life (MSQoL) Role Function-Restrictive Domain Score at Week 12 of the DBT Phase.	The change from baseline is calculated as the MSQoL restrictive role function domain score at Week 12 of the DBT phase minus the MSQoL restrictive role function domain score at baseline.	Week 12 of the double-blind treatment phase.
Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 of the DBT Phase.	The change from baseline is calculated as the MIDAS total score at Week 12 of the DBT phase minus the MIDAS total score at baseline.	Week 12 of the double-blind treatment phase.
Evaluate the safety and tolerability of zavegepant.	This will be evaluated by the number of participants with treatment related adverse events by severity measured as mild, moderate, or severe.	From Baseline through Week 12
The frequency of ALT or AST elevations > 3x ULN, concurrently with bilirubin elevations > 2x ULN in subjects treated with zavegepent during the double-blind and open label phases.		From Baseline through Week 12
The frequency of hepatic related adverse events.	Measured by discontinuations in subjects treated with zavegepant due to elevated Liver Function Tests during the double-blind and open label phases	From Baseline through Week 12

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, 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 26, 2021
• Primary Completion (Estimated): March 20, 2024
• Study Completion (Estimated): March 20, 2024

Study Registration Dates

• First Submitted: March 5, 2021
• First Submitted That Met QC Criteria: March 17, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Nausea; Migraine Prevention; Photophobia; 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: BHV3500-302; C5301006 (Other Identifier: Alias Study Number)

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: No