Acute Migraine Treatment in the ED With Gepants

NCT06985342 | Terminated Phase 4 FDA Drug

• 1 other identifier: STUDY-24-01677
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the effectiveness of rimegepant 75 mg orally disintegrating tablet (ODT) single-dose or zavegepant 10 mg nasal spray single-dose as acute migraine treatments during Emergency Department (ED) encounters. Although these two calcitonin gene-related peptide receptors (CGRP) receptor antagonists are FDA-approved for the indication of acute migraine treatment, past studies have been limited to the outpatient setting. If these medications are effective in the Emergency Department, their delivery methods alone may have advantages over intravenous medications commonly used for acute migraine in EDs, including quicker time to treatment delivery, faster pain relief, and reduced ED length of stay. This investigation is a pilot study to examine rimegepant and zavegepant in an ED, to gain insight on effectiveness in this setting. This study will administer rimegepant 75 mg ODT single-dose or zavegepant 10 mg nasal spray single-dose as acute migraine treatments to 100 patients in the Emergency Department. It is a single center, open-label, non-controlled 2-group clinical trial (allocated 1:1 to rimegepant or zavegepant via pseudo-random assignment). The study will enroll adults in the ED meeting ICHD-3 criteria for migraine or probable migraine, with or without aura.

Conditions

Migraine Headaches

Keywords

Migraine; Emergency Department; Gepants; CGRP antagonists; Rimegepant; Zavegepant

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with pain relief at 2 hours without rescue medication

  Percentage of participants reporting pain as 'mild' or 'none' at 2 hours post-study drug administration, without rescue medication. Pain is categorized as none, mild, moderate, or severe.

  120 minutes (2 hours)

Secondary Outcomes (2)

• Percentage of participants with pain relief at 2 hours post treatment

  120 minutes (2 hours) post treatment

• Percentage of participants with pain relief at 60 minutes post treatment

  60 minutes post treatment

Study Arms (2)

Rimegepant

EXPERIMENTAL

Participants in this arm will receive a single dose of rimegepant 75 mg orally disintegrating tablet (ODT) for acute migraine treatment during an Emergency Department (ED) encounter.

Drug: Rimegepant

Zavegepant

EXPERIMENTAL

Participants in this arm will receive a single dose of zavegepant 10 mg nasal spray for acute migraine treatment during an Emergency Department (ED) encounter.

Drug: Zavegepant

Interventions

Rimegepant DRUG

Rimegepant 75 mg orally disintegrating tablet (ODT), administered as a single dose

Rimegepant

Zavegepant DRUG

Zavegepant 10 mg nasal spray, administered as a single dose

Zavegepant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• 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 Legally Authorized Representative)
• Prior migraine diagnosis (clinical or self-reported)
• Emergency Department presentation for a headache fulfilling International Classification of Headache Disorders (ICHD-3) criteria for migraine with typical aura or without aura, or criteria for probable migraine with typical aura or without aura. Duration of migraines should be ≥ 1 year. It is acceptable if current headache duration is \>72 hours. Must have been headache free for \>48 hours prior to current attack.
• Willingness to participate in post-discharge telephone or electronic follow-up assessments

You may not qualify if:

• Suspected secondary headache due to another cause, or primary headache disorder other than migraine or probable migraine
• Prior healthcare encounter for headache within 7 days
• Use of analgesics or abortive headache medications within 2 hours of consent
• Use of intranasal decongestant within 12 hours of consent
• 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 cardiovascular disease, hypertension, or diabetes, recently diagnosed or currently uncontrolled or unstable
• History of stroke, peripheral vascular disease, or medically-diagnosed Raynaud's Phenomenon
• History of severe hepatic impairment, as assessed by the investigator or qualified delegate
• History of kidney disease stage 4 (creatinine clearance \<30 mL/min or eGFR \<35 mL/min/1.73 m2)
• History of nasal condition that may affect zavegepant administration, as assessed by the investigator or qualified delegate
• 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

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Pfizer: collaborator

Study Sites (1)

Mount Sinai Hospital

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Migraine Disorders; Emergencies

Interventions

rimegepant sulfate

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jonathan Schimmel

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: May 22, 2025
• Study Start: June 5, 2025
• Primary Completion: January 6, 2026
• Study Completion: February 4, 2026
• Last Updated: April 29, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)