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NCT04408794

Long-term Safety Study of BHV-3500 (Zavegepant*) for the Acute Treatment of Migraine

Completed Phase 2, PHASE3 Results posted Last updated 18 May 2023
What this trial tests

Phase 2, PHASE3 trial testing Zavegepant (BHV-3500) in Acute Migraine in 974 participants. Completed in 23 December 2021.

Timeline
29 June 2020
Primary endpoint
9 December 2021
23 December 2021

Quick facts

Lead sponsorPfizer
PhasePhase 2, PHASE3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment974
Start date29 June 2020
Primary completion9 December 2021
Estimated completion23 December 2021
Sites67 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Acute Migraine. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number Of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading To Discontinuation Primary · From study drug dosing up to the end of the study (up to 52 weeks)

An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in participants or clinical investigation participants administered an investigational (medicinal) product that does not necessarily have a causal relationship with this treatment. An SAE was defined as any event that met any of the following criteria at any dose: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received study

AEs
GroupValue95% CI
Zavegepant 10 mg460
SAEs
GroupValue95% CI
Zavegepant 10 mg7
AEs leading to discontinuation
GroupValue95% CI
Zavegepant 10 mg41
Number Of Participants With Clinically Significant Laboratory Abnormalities Primary · From study drug dosing up to the end of the study (up to 52 weeks)

Clinically significant laboratory abnormalities were defined as Grades 3 to 4 laboratory test results according to numeric laboratory test criteria found in Common Technical Criteria for Adverse Events Version 5.0 (2017) if available; otherwise, according to Division of Acquired Immune Deficiency Syndrome. Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 (2017) for glucose, low-density lipoprotein (LDL)-cholesterol, uric acid, and urinalysis. Laboratory test groups of clinical interest included hematology, serum chemistry, and urinalysis. Participants

Alanine Aminotransferase
GroupValue95% CI
Zavegepant 10 mg3
Aspartate Aminotransferase
GroupValue95% CI
Zavegepant 10 mg5
Albumin
GroupValue95% CI
Zavegepant 10 mg0
Alkaline Phosphatase
GroupValue95% CI
Zavegepant 10 mg0
Bicarbonate
GroupValue95% CI
Zavegepant 10 mg0
Biliburin
GroupValue95% CI
Zavegepant 10 mg0
Calcium, low
GroupValue95% CI
Zavegepant 10 mg0
Calcium, high
GroupValue95% CI
Zavegepant 10 mg0

Adverse events — posted to ClinicalTrials.gov

Time frame: From study drug dosing up to the end of the study (up to 52 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Zavegepant 10 mg
Serious: 7/603 (1%)
Deaths: 0/603

Serious adverse events (9 terms)

ReactionSystemZavegepant 10 mg
AppendicitisInfections and infestations
Herpes zoster meningoencephalitisInfections and infestations
PneumoniaInfections and infestations
Bile duct stenosisHepatobiliary disorders
ConcussionInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
Multiple sclerosisNervous system disorders
PleurisyRespiratory, thoracic and mediastinal disorders
Other adverse events (7 terms — click to expand)

ReactionSystemZavegepant 10 mg
DysgeusiaNervous system disorders
Nasal discomfortRespiratory, thoracic and mediastinal disorders
COVID-19Infections and infestations
NauseaGastrointestinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Throat irritationRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Appendicitis, Herpes zoster meningoencephalitis, Pneumonia, Bile duct stenosis, Concussion, Fall, Back pain, Multiple sclerosis.

Data from ClinicalTrials.gov NCT04408794 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the long-term safety of BHV-3500/vazegepant intranasal in the acute treatment of migraine. \* BHV-3500, formerly "vazegepant", is now referred to as "zavegepant" (za ve' je pant). The World Health Organization (WHO) International Nonproprietary Names (INN) Expert Committee revised the name to "zavegepant" which was accepted by the United States Adopted Names (USAN ) Council for use in the U.S. and is pending formal adoption by the INN for international use.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations.
    Koo J, Lim C, Oh KT. · · 2024 · cited 57× · PMID 38414526 · DOI 10.2147/ijn.s439181
  2. Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders.
    Patharapankal EJ, Ajiboye AL, Mattern C, Trivedi V. · · 2023 · cited 37× · PMID 38258077 · DOI 10.3390/pharmaceutics16010066
  3. Gepants - a long way to cure: a narrative review.
    Altamura C, Brunelli N, Marcosano M, Fofi L, et al · · 2022 · cited 32× · PMID 35650458 · DOI 10.1007/s10072-022-06184-8
  4. Zavegepant: First Approval.
    Dhillon S. · · 2023 · cited 26× · PMID 37227596 · DOI 10.1007/s40265-023-01885-6
  5. Therapeutic Advances in Diabetes, Autoimmune, and Neurological Diseases.
    Liu J, Ting JP, Al-Azzam S, Ding Y, et al · · 2021 · cited 15× · PMID 33802091 · DOI 10.3390/ijms22062805
  6. New Oral Drugs for Migraine.
    Karsan N, Goadsby PJ. · · 2022 · cited 12× · PMID 36031682 · DOI 10.1007/s40263-022-00948-8
  7. Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications.
    Özge A, Baykan B, Bıçakçı Ş, Ertaş M, et al · · 2024 · cited 11× · PMID 38938785 · DOI 10.3389/fneur.2024.1402569
  8. Long-term safety of zavegepant nasal spray for the acute treatment of migraine: A phase 2/3 open-label study.
    Mullin K, Croop R, Mosher L, Fullerton T, et al · · 2024 · cited 8× · PMID 39210835 · DOI 10.1177/03331024241259456

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