MigraineGAINERNCT05903027
Gepant treAtments: EffectIveNess and tolERability (GAINER)
An observational study of Migraine and Migraine With Aura, run by University of Florence at 2 sites in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Migraine, Migraine With Aura, Migraine Without Aura
- What is being tested?
- Rimegepant 75 MG Disintegrating Oral Tablet
- Type of treatment
- Pill or oral medicine
- How many people
- 100 participants
- Where
- 2 sitesItaly
- Study dates
- 15 Jun 2023to 15 Sep 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Multicentric study on patients attending the outpatient clinic of Italian Headache centres who meet criteria for Rimegepant use for acute migraine treatments.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Roberto De Icco, MD contact
Italy2 sites, 2 recruiting
- Recruiting
SOD Centro Cefalee e Farmacologia Clinica, AOU Careggi
Florence, 50134
Luigi F Iannone, MD, luigifrancesco.iannone@unimore.it
- Recruiting
IRCCS National Neurological Institute "C. Mondino" Foundation
Pavia, 27100
Roberto De Icco, MD, roberto.deicco@mondino.it
About this study
Official title: 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.
Read the 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.
- Conditions
- Migraine, Migraine With Aura, Migraine Without Aura, Chronic Migraine
- Being tested
- Rimegepant 75 MG Disintegrating Oral Tablet
- Keywords
- Headache, Medication overuse headache, Pain, Gepant, Triptan
- Medical subject headings
- Migraine Disorders, Migraine with Aura, Migraine without Aura, Headache, Headache Disorders, Secondary, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rimegepant 75 MG Disintegrating Oral TabletDrug
Patients using Rimegepant 75 mg orally disintegrating tablet to treat acute migraine attacks
| Study group | Role | What they receive |
|---|---|---|
| Episodic migraine | Patients affected by an episodic pattern migraine(< 15 monthly headache days) with or without aura according to ICHD-III criteria. Receives: Drug: Rimegepant 75 MG Disintegrating Oral Tablet | |
| Chronic migraine | Patients affected by chronic migraine according to ICHD-III criteria. Receives: Drug: Rimegepant 75 MG Disintegrating Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 2 hours post-dose
Occurrence of treatment-emergent adverse events
To evaluate the safety and tolerability of Rimegepant in migraine subjects.
Measured: 12 weeks
Secondary outcomes (10)
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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 2 hours post-dose
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.
Measured: 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).
Measured: 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.
Measured: 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)
Measured: 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).
Measured: 2 hours post-dose for all treated attacks
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start15 Jun 2023
- Primary completion15 Jun 2024
- Study completion15 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florence
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS National Neurological Institute "C. Mondino" Foundation, Società Italiana per lo Studio delle Cefalee, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Università degli Studi dell'Aquila, University of Roma La Sapienza, Azienda Ospedaliero Universitaria Policlinico Modena, ULSS6 - Ospedale di Piove di Sacco, Azienda Ospedaliero-Universitaria di Parma, Azienda Ospedaliera S. Maria della Misericordia, A.O.U. Città della Salute e della Scienza, Cliniche Humanitas Gavazzeni, University of Campania Luigi Vanvitelli, Ospedale Santo Stefano, Azienda Policlinico Umberto I, Auxologico San Luca, Asst Degli Spedali Civili Di Brescia, Carlo Besta Neurological Institute
- Responsible party
- Principal investigator, Luigi Francesco Iannone, University of Florence
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05903027
- Sponsor's protocol ID
- RICe_1
- Acronym
- GAINER
- Status last verified
- Jan 2026
- First submitted
- 5 Jun 2023
- Last updated
- 21 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 31291516Croop 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.
PubMed 31311674Lipton 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.
PubMed 36739511Iannone 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.
PubMed 39762740
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness and Tolerability of Rimegepant as Acute Migraine Treatment: a Prospective, Multicentric, Cohort Study (GAINER)
- ClinicalTrials.gov ID
- NCT05903027
- Acronym / sponsor ID
- GAINER / RICe_1
- Conditions
- Migraine, Migraine With Aura, Migraine Without Aura, Chronic Migraine
- Keywords
- Headache, Medication overuse headache, Pain, Gepant, Triptan
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of FlorenceUniversity, hospital or other
- Collaborators
- IRCCS National Neurological Institute "C. Mondino" Foundation, Società Italiana per lo Studio delle Cefalee, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Università degli Studi dell'Aquila, University of Roma La Sapienza, Azienda Ospedaliero Universitaria Policlinico Modena, ULSS6 - Ospedale di Piove di Sacco, Azienda Ospedaliero-Universitaria di Parma, Azienda Ospedaliera S. Maria della Misericordia, A.O.U. Città della Salute e della Scienza, Cliniche Humanitas Gavazzeni, University of Campania Luigi Vanvitelli, Ospedale Santo Stefano, Azienda Policlinico Umberto I, Auxologico San Luca, Asst Degli Spedali Civili Di Brescia, Carlo Besta Neurological Institute
- Study start
- 15 Jun 2023 (actual)
- Primary completion
- 15 Jun 2024 (actual)
- Study completion
- 15 Sep 2026 (estimated)
- First posted
- 15 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Episodic migraine | – | Drug: Rimegepant 75 MG Disintegrating Oral TabletPatients affected by an episodic pattern migraine(< 15 monthly headache days) with or without aura according to ICHD-III criteria. |
| Chronic migraine | – | Drug: Rimegepant 75 MG Disintegrating Oral TabletPatients affected by chronic migraine according to ICHD-III criteria. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Multicentric study on patients attending the outpatient clinic of Italian Headache centres who meet criteria for Rimegepant use for acute migraine treatments.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rimegepant 75 MG Disintegrating Oral TabletPatients using Rimegepant 75 mg orally disintegrating tablet to treat acute migraine attacks | Drug | Chronic migraine, Episodic migraine |
Primary outcome
Headache pain freedom at 2 hours post-dose during the first attack
Time frame: 2 hours post-dose
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).
Occurrence of treatment-emergent adverse events
Time frame: 12 weeks
To evaluate the safety and tolerability of Rimegepant in migraine subjects.
10 secondary outcomes
Headache pain freedom at 2 hours post-dose across all treated attacks
Time frame: 2 hours post-dose for all treated attacks
Headache pain relief at 2 hours post-dose during the first attack
Time frame: 2 hours post-dose
Headache pain relief at 2 hours post-dose across all treated attacks
Time frame: 2 hours post-dose for all treated attacks
Ability to function normally at 2 hours post-dose during the first attack
Time frame: 2 hours post-dose
Ability to function normally at 2 hours post-dose across all treated attacks
Time frame: 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
Time frame: 2 hours post-dose
Headache recurrence for the first-attack
Time frame: between 2 hours and 24 hours post-dose
Rescue medications use for the first attack
Time frame: between 2 hours and 24 hours post dose
Treatment satisfaction
Time frame: 2 hours post-dose for all treated attacks
Self-reported treatment effectiveness
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2026.
- Background: PubMed 31291516Lipton 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.
- Background: PubMed 31311674Croop 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.
- Background: PubMed 36739511Lipton 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.
- Derived from this study: PubMed 39762740Iannone 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Roberto De Icco, MD contact
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Migraine and Migraine With Aura, run by University of Florence at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Luigi F Iannone, MD (+393896969606, luigifrancesco.iannone@unifi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Headache pain freedom at 2 hours post-dose during the first attack (time frame: 2 hours post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05903027, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.