Effectiveness and Tolerability of Zavegepant for Acute Migraine Treatment Among Those Using CGRP Targeting Preventive Medications

A Study to Assess Effectiveness and Tolerability of Zavegepant as an Acute Migraine Treatment Among Those Using CGRP Targeting Preventive Medications.

Zavegepant (Zavzpret) is approved for the acute treatment of migraine with or without aura in the US. The purpose of this study is to investigate the effectiveness and tolerability of zavegepant for the acute treatment of migraine attacks amongst participants who are using calcitonin gene-related peptide (CGRP) migraine preventive treatments.

Study Overview

• Status: Recruiting
• Conditions: Migraine
• Intervention / Treatment: Drug: Zavegepant

Detailed Description

This is a phase IV, open-label, prospective, longitudinal clinical trial of intranasal zavegepant 10 mg, a CGRP receptor antagonist, for the acute treatment of migraine attacks amongst individuals who are concomitantly taking stable doses of CGRP targeting migraine preventive treatment (atogepant, eptinezumab, erenumab, fremanezumab, galcanezumab, rimegepant). The effectiveness and tolerability of zavegepant will be assessed in this specific participant population. Participants who are not already taking a CGRP-targeting migraine preventive treatment but who meet criteria for migraine prevention according to their clinician's discretion, will have the option to start rimegepant 75 mg every other day (qod) for two months. After two months, continued eligibility for participation in the clinical trial of zavegepant will be assessed. Those receiving rimegepant for migraine prevention through their participation in this study will have the option to receive rimegepant for up to 32 consecutive weeks.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85254
      • Recruiting
      • Mayo Clinic in Arizona
      • Contact: Michael R Leonard; Phone Number: 480-342-2908; Email: Leonard.Michael@Mayo.edu
      • Principal Investigator: Todd J Schwedt, MD
      • Contact: Dani SMith; Phone Number: 480-342-6524; Email: Smith.Dani@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Meets International Classification of Headache Disorders 3 (ICHD-3) diagnostic criteria for migraine with or without aura
• At least 18 years of age
• 2- 8 migraine attacks per month

• Participants should be on a calcitonin gene-related peptide (CGRP)-targeting preventive migraine medication on a stable dose for a) ≥2 months prior to zavegepant treatment if an oral gepant or a monoclonal antibody (mAb) injected monthly, or b) at least two treatments if a mAb injected each 3 months.

  • Atogepant
  • Eptinezumab
  • Erenumab
  • Fremanezumab
  • Galcanezumab
  • Rimegepant

Exclusion Criteria

• Primary headache disorders other than migraine (tension-type headache days are allowed)
• History of hypersensitivity reaction to zavegepant or to any of the components of zavegepant

Eligibility Notes

• Participants may have either episodic or chronic migraine.
• Prior use of zavegepant and other gepants is permitted.
• Participants can be using migraine preventive medications/treatments in addition to the CGRP-targeting preventive treatment, as long as those treatments have been stable for at least two months at the time of enrollment.

Additional Eligibility Criteria for Participants to Start on Rimegepant for Migraine Prevention

Inclusion Criteria:

• Must have 4 or more migraine days per month, on average, during the 2 months prior to the Screening Visit, according to participant self-report.

Exclusion Criteria

• History of hypersensitivity reaction to rimegepant or to any of the components of rimegepant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zavegepant Treatment; Participants will receive zavegepant to treat up to 8 migraine attacks over 24 weeks.	Drug: Zavegepant; 10 mg intranasal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache relief in 2 hours	Percentage of participants who have meaningful headache relief within 2 hours of administering zavegepant	2 hours
Headache relief in 4 hours	Percentage of participants who have meaningful headache relief within 4 hours of administering zavegepant	4 hours
Functional disability level in 2 hours	Percentage of participants with functional disability level of normal or mildly impaired within 2 hours of administering zavegepant.	2 hours
Functional disability level in 4 hours	Percentage of participants with functional disability level of normal or mildly impaired within 4 hours of administering zavegepant.	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Percentage of participants and treated migraine attacks with treatment emergent adverse events	Approximately 24-32 weeks
Serious adverse events	Percentage of participants and treated migraine attacks with serious treatment emergent adverse events	Approximately 24-32 weeks
Discontinuation due to adverse events	Percentage of participants who discontinue zavegepant due to adverse events	Approximately 24-32 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Todd Schwedt, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Zavegepant to Treat Migraine Attacks

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: May 2, 2024
• First Submitted That Met QC Criteria: May 2, 2024
• First Posted (Actual): May 7, 2024

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 23-011210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No