Clinical trial NCT04804033: A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention
Official title: A Phase 2/3 Randomized, Double-Blind, Placebo- Controlled Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Migraine
Keywords: Migraine Prevention
Phonophobia
Photophobia
Nausea
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-03-18
Enrollment: 1753
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Mean Change From Observation Phase (OP) in the Number of Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12)
timeFrame: Observation Phase: 28 days prior to randomization and baseline; Entire DBT Phase: 12 weeks (Week 1 through 12)
Secondary outcomes:
measure: Percentage of Participants With >= 50 % Reduction in Number of Moderate to Severe Migraine Days Per Month Over Entire DBT Phase (Weeks 1 to 12)
timeFrame: Entire DBT Phase: 12 weeks (Week 1 through 12)
measure: Mean Change From Observation Phase in the Number of Migraine Days Per Month in the Last 4 Weeks (Weeks 9 to 12) of DBT Phase
timeFrame: Observation Phase: 28 days prior to randomization and baseline; DBT Phase: last 4 weeks (Week 9 through 12)
measure: Mean Change From Observation Phase in the Number of Migraine Days Per Month in the First 4 Weeks (Weeks 1 to 4) of DBT Phase
timeFrame: Observation Phase: 28 days prior to randomization and baseline; DBT Phase: first 4 weeks (Week 1 through 4)
measure: Mean Number of Acute Migraine -Specific Medication Days Per Month Over Entire DBT Phase (Weeks 1 to 12)
timeFrame: Entire DBT Phase: 12 weeks (Week 1 through 12)
measure: Mean Change From Baseline in the Migraine-specific Quality of Life Questionnaire (MSQ) v 2.1 Restrictive Role Function Domain Score at Week 12
timeFrame: DBT Phase: Baseline (before dose on Day 1), Week 12
measure: Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12
timeFrame: DBT Phase: Baseline (before dose on Day 1), Week 12
measure: Number of Participants With Moderate or Severe Adverse Events (AEs): DBT Phase
timeFrame: DBT Phase: During 12 weeks of treatment
measure: Number of Participants With Serious Adverse Events (SAEs): DBT Phase
timeFrame: DBT Phase: During 12 weeks of treatment
measure: Number of Participants With AEs Leading to Study Drug Discontinuation: DBT Phase
timeFrame: DBT Phase: During 12 weeks of treatment
measure: Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: DBT Phase
timeFrame: DBT: During 12 weeks of treatment
measure: Number of Participants With Moderate or Severe AEs: OLE Phase
timeFrame: OLE: During 52 weeks of treatment
measure: Number of Participants With SAEs: OLE Phase
timeFrame: OLE: During 52 weeks of treatment
measure: Number of Participants With AEs Leading to Study Drug Discontinuation: OLE Phase
timeFrame: OLE: During 52 weeks of treatment
measure: Number of Participants With Grade 3 to 4 Laboratory Test Abnormalities: OLE Phase
timeFrame: OLE: During 52 weeks of treatment
measure: Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: DBT Phase
timeFrame: DBT: Over 12 weeks of treatment
measure: Percentage of Participants With AST or ALT Elevations >3 * ULN With Total Bilirubin > 2 * ULN: OLE Phase
timeFrame: OLE: Over 52 weeks of treatment
measure: Number of Participants With Hepatic-related AEs by Intensity: DBT Phase
timeFrame: DBT Phase: During 12 weeks of treatment
measure: Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: DBT Phase
timeFrame: DBT Phase: During 12 weeks of treatment
measure: Number of Participants With Hepatic-related AEs by Intensity: OLE Phase
timeFrame: OLE: Over 52 weeks of treatment
measure: Number of Participants With Hepatic-related AEs Leading to Study Drug Discontinuation: OLE Phase
timeFrame: OLE: Over 52 weeks of treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Xenoscience, Inc
state: Arizona
city: Tucson
country: United States
facility: Tucson Neuroscience Research
state: Arizona
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Colton
country: United States
facility: Axiom Research, Llc
state: California
city: Encino
country: United States
facility: Wr-Pri, Llc
state: California
city: La Mesa
country: United States
facility: eStudySite
state: California
city: Lemon Grove
country: United States
facility: Synergy San Diego
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research, LLC.
state: California
city: Los Angeles
country: United States
facility: Clinical Research Institute
state: California
city: Newport Beach
country: United States
facility: Wr-Pri, Llc
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, inc.
state: California
city: Hamden
country: United States
facility: CMR of Greater New Haven, LLC
state: Connecticut
city: Stamford
country: United States
facility: Ki Health Partners, LLc, dba New England Institute for Clinical Research
state: Connecticut
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Boca Raton
country: United States
facility: Neurology Offices of South Florida
state: Florida
city: Edgewater
country: United States
facility: Accel Research Sites Network - Edgewater Clinical Research Unit
state: Florida
city: Edgewater
country: United States
facility: Complete Health Research
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Lake City
country: United States
facility: Multi-Specialty Research Associates, Inc.
state: Florida
city: Miami
country: United States
facility: AppleMed Research Group, LLC
state: Florida
city: Miami
country: United States
facility: AppleMed Research Group, LLC
state: Florida
city: Miami
country: United States
facility: Brainstorm Research
state: Florida
city: Miami
country: United States
facility: The Neurology Research Group
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Ormond Beach
country: United States
facility: Complete Health Research
state: Florida
city: Pembroke Pines
country: United States
facility: Ideal Clinical Research
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida
state: Florida
city: Saint Petersburg
country: United States
facility: Accel Research Sites Network - St. Petersburg Clinical Research Unit
state: Florida
city: South Miami
country: United States
facility: Clin-Med Research & Development LLC
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
city: Tampa
country: United States
facility: JSV Clinical Research Study Inc
state: Florida
city: Decatur
country: United States
facility: CenExel iResearch, LLC
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta LLC
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Gurnee
country: United States
facility: Clinical Investigation Specialists, Inc.
state: Illinois
city: Gurnee
country: United States
facility: Clinical Investigation Specialists, Inc
state: Illinois
city: Evansville
country: United States
facility: MediSphere Medical Research Center, LLC.
state: Indiana
city: Evansville
country: United States
facility: MediSphere Medical Research Center, LLC
state: Indiana
city: Sioux City
country: United States
facility: Meridian Clinical Research, LLC
state: Iowa
city: El Dorado
country: United States
facility: Alliance for Multispecialty Reseach, LLC
state: Kansas
city: Newton
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Overland Park
country: United States
facility: Collevtive Medical Research
state: Kansas
city: Overland Park
country: United States
facility: Kansas Institute of Research
state: Kansas
city: Lexington
country: United States
facility: The Research Group of Lexington, Llc.
state: Kentucky
city: Lexington
country: United States
facility: The Research Group of Lexington, Llc
state: Kentucky
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Chalmette
country: United States
facility: Crescent City Headache and Neurology Center
state: Louisiana
city: New Orleans
country: United States
facility: Alliance for Multispecialty Research, LLC.
state: Louisiana
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: Boston
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Foxboro
country: United States
facility: Neurology Center of New England P.C.
state: Massachusetts
city: Marlborough
country: United States
facility: Community Clinical Research Network Inc
state: Massachusetts
city: Waltham
country: United States
facility: MedVadis Research Corporation
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Head Pain & Neurological Institute
state: Michigan
city: Rochester
country: United States
facility: Romedica LLC
state: Michigan
city: Kansas City
country: United States
facility: Alliance for Multispecialty Reseach, LLC
state: Missouri
city: Saint Peters
country: United States
facility: StudyMetrix Research
state: Missouri
city: Springfield
country: United States
facility: Clinvest Research, LLC
state: Missouri
city: Springfield
country: United States
facility: Clinvest Research, LLC
state: Missouri
city: Norfolk
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Excel Clinical research
state: Nevada
city: Las Vegas
country: United States
facility: Wr-Crcn, Llc
state: Nevada
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc.
state: New Mexico
city: Amherst
country: United States
facility: Dent Neurosciences Research Center, Inc.
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Manlius
country: United States
facility: Central New York Clinical Research
state: New York
city: New York
country: United States
facility: New York Neurology Associates
state: New York
city: New York
country: United States
facility: Fieve Clinical Research, Inc
state: New York
city: Port Jefferson Station
country: United States
facility: North Suffolk Neurology, PC
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates, LLC
state: New York
city: Greensboro
country: United States
facility: Headache Wellness Center
state: North Carolina
city: Raleigh
country: United States
facility: Accellacare
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research, Inc.
state: North Carolina
city: Shelby
country: United States
facility: Carolina Research Center, Inc.
state: North Carolina
city: Wilmington
country: United States
facility: Accellacare
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Cincinnati
country: United States
facility: WellNow Urgent Care and Research
state: Ohio
city: Cincinnati
country: United States
facility: Wellnow Urgent Care
state: Ohio
city: Columbus
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Columbus
country: United States
facility: Wellnow Urgent Care and Research
state: Ohio
city: Dayton
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Dayton
country: United States
facility: WellNow Urgent Care and Research
state: Ohio
city: North Canton
country: United States
facility: Neuro-Behavioral Clinical Research, Inc.
state: Ohio
city: Troy
country: United States
facility: WellNow Urgent Care and Research
state: Ohio
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: Portland
country: United States
facility: Summit Headlands LLC, dba Summit Research
state: Oregon
city: Philadelphia
country: United States
facility: Clinical Research Philadelphia, LLC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Inc.
state: Pennsylvania
city: Uniontown
country: United States
facility: Preferred Primary Care Physicians
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital Clinical Trials Office
state: Pennsylvania
city: West Reading
country: United States
facility: Tower Health Medical Group - Neurology
state: Pennsylvania
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Bristol
country: United States
facility: Accellacare (Administrative Only)
state: Tennessee
city: Bristol
country: United States
facility: Internal Medicine and Pediatric Associates of Bristol, PC
state: Tennessee
city: Chattanooga
country: United States
facility: WR-ClinSearch, LLC
state: Tennessee
city: Franklin
country: United States
facility: KCA Neurology, PLLC
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, LP
state: Texas
city: Frisco
country: United States
facility: North Texas Institute of Neurology and Headache - NextStage Clinical Research
state: Texas
city: Frisco
country: United States
facility: North Texas Institute of Neurology and Headache
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
city: Lake Jackson
country: United States
facility: Red Star Research. LLC
state: Texas
city: Lampasas
country: United States
facility: FMC Science
state: Texas
city: Lampasas
country: United States
facility: Radiance Clinical Research
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research , LLC(Administrative Location)
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center, LLC
state: Virginia
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc.
state: Virginia
city: Norfolk
country: United States
facility: Meridian Clinical Research, LLC
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: Seattle Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: Seattle Women's: Health, Research, Gynecology
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: