Gepant treAtments: EffectIveNess and tolERability (GAINER) (GAINER)

Effectiveness and Tolerability of Rimegepant as Acute Migraine Treatment: a Prospective, Multicentric, Cohort Study (GAINER)

The purpose of this prospective and multicentric study is to evaluate the effectiveness and tolerability of rimegepant as acute migraine treatment in a cohort of episodic or chronic migraine patients.

Study Overview

• Status: Recruiting
• Conditions: Migraine; Chronic Migraine; Migraine Without Aura; Migraine With Aura
• Intervention / Treatment: Drug: Rimegepant 75 MG Disintegrating Oral Tablet

Detailed Description

Rimegepant belongs to the gepants family, small molecules calcitonin gene-related peptide (CGRP) receptor antagonists. It is a new generation gepants, currently available as an orally disintegrating tablet at a single dose of 75 mg. It has a double indication both for acute treatment for migraine with and without aura and preventive treatment of episodic migraine. Previous randomized, placebo-controlled phase 3 trials and open label extensions demonstrated its effectiveness in the acute setting for a single migraine attack of both the oral tablet and the orally disintegrating tablet. Pooled analysis of previous randomized clinical trials also showed rimegepant effectiveness in patients with a history of insufficient response to triptans.

Previous studies also demonstrated a good tolerability profile. The most commonly reported adverse events were nausea, nasopharyngitis, upper respiratory tract infections and urinary tract infection.

In this prospective multicentric study we aim to evaluate Rimegepant effectiveness and tolerability as acute migraine treatment in a real-world setting.

Subjects who meet the inclusion criteria will be enrolled and will participate in the study. Baseline demographic and clinical data will be collected at the baseline. Patients will be asked to treat their next migraine attack with Rimegepant 75 mg orally disintegrating tablet.

Data will be collected at baseline, during at least 4 migraine attacks treated with Rimegepant and at 3 months follow-up.

Subjects will be asked to complete assessment of their migraine attack at baseline and at 30 - 60 - 90 and 120 minutes after administration of the acute treatment for at least four migraine attacks. A final timepoint at 24 hours post-dose will be assessed only for the first attack.

Data collection will focus on: i) demographic data, ii) migraine history, iii) pain level and evolution, iv) presence and evolution of migraine associated symptoms, most bothersome symptom and aura, v) migraine associated disability, vi) patients's global impression of change (PGIC) and evaluation on the acute treatment (Migraine-ACT), vii) tolerability and eventual treatment-emergent adverse events. The online database REDCap will be used for data collection.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Luigi F Iannone, MD; Phone Number: +393896969606; Email: luigifrancesco.iannone@unifi.it
• Study Contact Backup: Name: Roberto De Icco, MD; Email: roberto.deicco@mondino.it

Study Locations

• Italy
  • Florence, Italy, 50134
    • Recruiting
    • SOD Centro Cefalee e Farmacologia Clinica, AOU Careggi
    • Contact: Luigi F Iannone, MD; Email: luigifrancesco.iannone@unimore.it
  • Pavia, Italy, 27100
    • Recruiting
    • IRCCS National Neurological Institute "C. Mondino" Foundation
    • Contact: Roberto De Icco, MD; Email: roberto.deicco@mondino.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Multicentric study on patients attending the outpatient clinic of Italian Headache centres who meet criteria for Rimegepant use for acute migraine treatments.

Description

Inclusion Criteria:

• Diagnosis of migraine without aura, migraine with aura, or chronic migraine according to the 3rd edition of the International Classification of Headache Disorder (ICHD-III).
• At least 3 MMDs
• Good compliance to study procedures
• Availability of headache diary at least of the preceding months before enrollment

Exclusion Criteria:

• Subjects with contraindications for use of gepants;
• Concomitant diagnosis of medical diseases and/or comorbidities that, in the Investigator's opinion might interfere with study assessments;
• medical comorbidities that could interfere with study results;
• Pregnancy and breastfeeding.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Episodic migraine; Patients affected by an episodic pattern migraine(< 15 monthly headache days) with or without aura according to ICHD-III criteria.	Drug: Rimegepant 75 MG Disintegrating Oral Tablet; Patients using Rimegepant 75 mg orally disintegrating tablet to treat acute migraine attacks
Chronic migraine; Patients affected by chronic migraine according to ICHD-III criteria.	Drug: Rimegepant 75 MG Disintegrating Oral Tablet; Patients using Rimegepant 75 mg orally disintegrating tablet to treat acute migraine attacks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache pain freedom at 2 hours post-dose during the first attack	The percentage of subjects that report no headache pain at 2 hours after drug intake. Pain will be measured on a 4 point Likert scale (0=none, 1=mild, 2=moderate, 3=severe).	2 hours post-dose
Occurrence of treatment-emergent adverse events	To evaluate the safety and tolerability of Rimegepant in migraine subjects.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache pain freedom at 2 hours post-dose across all treated attacks	The percentage of subjects that report no headache pain at 2 hours after drug intake across all' treated attacks. Pain will be measured on a 4 point Likert scale (0=none, 1=mild, 2=moderate, 3=severe).	2 hours post-dose for all treated attacks
Headache pain relief at 2 hours post-dose during the first attack	The percentage of subjects that report mild or none headache pain at 2 hours after drug intake during the first attack. Pain will be measured on a 4 point Likert scale (0=none, 1=mild, 2=moderate, 3=severe).	2 hours post-dose
Headache pain relief at 2 hours post-dose across all treated attacks	The percentage of subjects that report mild or none headache pain at 2 hours after drug intake across all treated attack. Pain will be measured on a 4 point Likert scale (0=none, 1=mild, 2=moderate, 3=severe).	2 hours post-dose for all treated attacks
Ability to function normally at 2 hours post-dose across all treated attacks	The percentage of subjects that self-report no functional disability at 2 hours post-dose. Functional disability will be assessed through the Functional Disability Scale, a four-point scale: normal, mildly impaired, severely impaired, requires daily activities interruption.	2 hours post-dose for all treated attacks
Freedom from the most bothersome symptom (MBS) associated with migraine at 2 hours post-dose during the first attack	The percentage of subjects that report complete MBS resolution at 2 hours after drug intake. MBS will be measured on a 4 point Likert scale (0=none, 1=mild, 2=moderate, 3=severe).	2 hours post-dose
Headache recurrence for the first-attack	Percentage of subjects who became pain free at 2 hours post-dose and report new headache pain within 24 hours post-dose.	between 2 hours and 24 hours post-dose
Rescue medications use for the first attack	Percentage of subjects who take a rescue medication after 2 hour post-dose. Rescue medications will be measured using a binary scale (0=no consumption, 1=consumption)	between 2 hours and 24 hours post dose
Treatment satisfaction	Level of patients' self-reported satisfaction which will be measured on a 0-10 visual analogue scale (0=no satisfaction, 10= the highest satisfaction) and Patients Global Impression of Change (0= no changing, 7= a change that makes the difference).	2 hours post-dose for all treated attacks
Ability to function normally at 2 hours post-dose during the first attack	The percentage of subjects that self-report no functional disability at 2 hours post-dose. Functional disability will be assessed through the Functional Disability Scale (FDS), a four-point scale: normal, mildly impaired, severely impaired, requires daily activities interruption.	2 hours post-dose
Self-reported treatment effectiveness	Level of patients' self-reported treatment effectiveness measured by Migraine Assessment of Current Therapy (Migraine-ACT) a 4-item questionnaire about treatment effectiveness and daily life repercussions.	12 weeks

Collaborators and Investigators

• Sponsor: University of Florence
• Collaborators: University of Roma La Sapienza; Azienda Ospedaliero-Universitaria di Parma; Azienda Ospedaliera S. Maria della Misericordia; IRCCS National Neurological Institute "C. Mondino" Foundation; Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari; Università degli Studi dell'Aquila; Azienda Policlinico Umberto I; Cliniche Humanitas Gavazzeni; Carlo Besta Neurological Institute; Ospedale Santo Stefano; Azienda Ospedaliero Universitaria Policlinico Modena; Ospedale di Piove di Sacco; A.O.U. Città della Salute e della Scienza; Asst Degli Spedali Civili Di Brescia; University of Campania Luigi Vanvitelli; Società Italiana per lo Studio delle Cefalee; Auxologico San Luca

Publications and helpful links

General Publications

• Lipton RB, Croop R, Stock EG, Stock DA, Morris BA, Frost M, Dubowchik GM, Conway CM, Coric V, Goadsby PJ. Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine. N Engl J Med. 2019 Jul 11;381(2):142-149. doi: 10.1056/NEJMoa1811090.
• Croop R, Goadsby PJ, Stock DA, Conway CM, Forshaw M, Stock EG, Coric V, Lipton RB. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019 Aug 31;394(10200):737-745. doi: 10.1016/S0140-6736(19)31606-X. Epub 2019 Jul 13.
• Lipton RB, Blumenfeld A, Jensen CM, Croop R, Thiry A, L'Italien G, Morris BA, Coric V, Goadsby PJ. Efficacy of rimegepant for the acute treatment of migraine based on triptan treatment experience: Pooled results from three phase 3 randomized clinical trials. Cephalalgia. 2023 Feb;43(2):3331024221141686. doi: 10.1177/03331024221141686.
• Iannone LF, Vaghi G, Sebastianelli G, Casillo F, Russo A, Silvestro M, Pistoia F, Volta GD, Cortinovis M, Chiarugi A, Montisano DA, Prudenzano MP, Cevoli S, Mampreso E, Avino G, Romozzi M, Valente M, Fasano C, Battistini S, Granato A, Piella EM, Rainero I, Ornello R, De Icco R; Italian Headache Registry (RICe) Study Group. Effectiveness and tolerability of rimegepant in the acute treatment of migraine: a real-world, prospective, multicentric study (GAINER study). J Headache Pain. 2025 Jan 6;26(1):4. doi: 10.1186/s10194-024-01935-8.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2023
• Primary Completion (Actual): June 15, 2024
• Study Completion (Estimated): September 15, 2026

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: June 5, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Pain; Headache; Medication overuse headache; Triptan; Gepant
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Migraine Disorders; Headache; Migraine with Aura; Migraine without Aura; Headache Disorders, Secondary; rimegepant sulfate
• Other Study ID Numbers: RICe_1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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