A Prospective, Open-Label Study Evaluating the Effectiveness of Gepants for Acute Treatment of Migraine in the Emergency Department

NCT07667621 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: STUDY009783
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective, single-site, open-label, non-controlled pilot study consisting of two parallel trials. Participants will receive rimegepant or zavegepant for acute migraine treatment during a single Emergency Department visit, with post-discharge follow-up through 28 days. Participants will be allocated to either the rimegepant trial or the zavegepant trial. The study design does not include a placebo or active comparator control group, and the two gepant study drugs are not designed to function as active comparator groups. The objective in this investigation is to examine relief from either rimegepant or zavegepant in separate parallel trials.

Conditions

Migraine; Migraine Disease; Migraine in Adults; Migraine Headache; Acute Migraine; Migraine Without Aura; Migraine With Aura

Outcome Measures

Primary Outcomes (1)

• Pain relief at 2 hours without rescue medication

  Evaluate the effectiveness of rimegepant 75 mg ODT or zavegepant 10 mg nasal spray as acute migraine treatments administered during ED encounters • Percentage of participants with pain relief of "mild" or "none" on a 4-point scale (none, mild, moderate, severe) at 2 hours post-study drug administration, without rescue medication

  2 hours post-study drug administration

Secondary Outcomes (2)

• Pain relief at 2 hours (with or without rescue medication)

  2 hours post-study drug administration

• Early pain relief at 60 minutes

  60 minutes post-study drug administration

Study Arms (2)

Rimegepant (Parallel Trial)

EXPERIMENTAL

Participants receive a single oral dose of rimegepant 75 mg orally disintegrating tablet during an Emergency Department visit for the acute treatment of migraine. This arm represents one of two independent, parallel pilot trials evaluating the effectiveness and safety of gepant medications in the Emergency Department. This arm is not intended for comparison with the zavegepant arm.

Drug: Rimegepant

Zavegepant (Parallel Trial)

EXPERIMENTAL

Participants receive a single dose of zavegepant 10 mg administered as an intranasal spray during an Emergency Department visit for the acute treatment of migraine. This arm represents one of two independent, parallel pilot trials evaluating the effectiveness and safety of gepant medications in the Emergency Department. This arm is not intended for comparison with the rimegepant arm.

Drug: Zavegepant

Interventions

Zavegepant DRUG

Zavegepant 10 mg nasal spray administered as a single spray into one nostril during an Emergency Department visit for the acute treatment of migraine. Administration is consistent with FDA-approved labeling

Zavegepant (Parallel Trial)

Rimegepant DRUG

Rimegepant 75 mg orally disintegrating tablet administered as a single dose during an Emergency Department visit for the acute treatment of migraine. The tablet is placed on or under the tongue and allowed to dissolve without water, consistent with FDA-approved labeling.

Rimegepant (Parallel Trial)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• Capacity to provide informed consent (without a Representative)
• Emergency Department presentation for a headache consistent with migraine, based either on the treating clinical team's judgement, or fulfillment of International Classification of Headache Disorders (ICHD-3) criteria for migraine without aura or with typical aura, or for probable migraine without aura or with typical aura. It is acceptable if current headache duration is \>72 hours. Must have been headache free for \>48 hours prior to current attack.
• Willing to participate in post-discharge telephone assessments
• English and/or Spanish speaking patients

You may not qualify if:

• Use of intranasal decongestants within 1 hour prior to study drug administration, due to the potential to decrease absorption of intranasal zavegepant.
• Use of analgesics or abortive headache medications within 60 minutes of study medication administration
• Use of the following drug/food categories with potential for drug interactions within 7 days or 5 half-lives, whichever is longer: 1) CYP3A strong or moderate inducers, 2) CYP3A4 strong inhibitors, 3) P-glycoprotein (P-gp) inhibitors, 4) OATP1B3 transporter potent inhibitors/inducers, 5) NTCP transporter potent inhibitors/inducers
• History of ischemic cardiovascular disease, diabetes, or hypertension (diagnosed or likely based on multiple readings), that was recently diagnosed within 3 months of screening or is currently uncontrolled or unstable
• History of any stroke within 3 months, or any lifetime stroke and age ≥65 years
• History of significant peripheral vascular disease, as assessed by the investigator or qualified delegate
• History of Raynaud's Phenomenon (medically diagnosed, or non-medically diagnosed with affirmative responses to both unusual sensitivity and finger color change with cold exposure)
• History of severe hepatic impairment, as assessed by the investigator or qualified delegate
• History of kidney disease stage 4 (eGFR \<30 mL/min/1.73 m2)
• History of hypersensitivity reaction to rimegepant, zavegepant, or to any included inactive ingredients
• Lifetime use of CGRP-targeting acute or preventive migraine medications
• In custody of law enforcement
• Current pregnancy or lactation
• All individuals of childbearing potential must have a negative pregnancy test at screening (urine or serum).
• A person is considered to be of childbearing potential if possessing female reproductive organs at birth, post-menarchal, has not reached a post-menopausal state (≥12 continuous months of amenorrhea with no cause identified other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis).

Sponsors & Collaborators

• University of South Florida: lead
• Pfizer: collaborator
• Tampa General Hospital: collaborator

Study Sites (1)

Tampa General Hospital Emergency Room

Tampa, Florida, 33606, United States

Location

MeSH Terms

Conditions

Migraine Disorders; Migraine without Aura; Migraine with Aura

Interventions

rimegepant sulfate

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chair of Research and Assistant Dean of Faculty Development, USF Health

Study Record Dates

• First Submitted: June 20, 2026
• First Posted: June 25, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: June 25, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)