Italian Real-life obServational Study on the effecTiveness, sAfety and Tolerability of Atogepant in Migraine Patients (STAR)

STudio Osservazionale Sull'Efficacia, Sicurezza e tollerabilità di Atogepant in Pazienti Real Life Affetti da Emicrania in Italia (Studio STAR)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Migraine; Chronic Migraine; Migraine Without Aura; Migraine With Aura
• Intervention / Treatment: Drug: Atogepant 60 mg

Detailed Description

Atogepant is a small molecule calcitonin gene- related peptide (CGRP) receptor antagonist, part of the gepants family. It is a second generation gepant, currently approved for the preventive treatment of episodic and chronic migraine.

Previously randomized, placebo-controlled phase 2/3 trials demonstrated its effectiveness and tolerability in the preventive setting for patients with episodic and chronic migraine, associated with a good tolerability profile.

The most commonly reported adverse events were upper respiratory tract infections, urinary infections, nausea and constipation.

In this prospective multicentric study the investigators aim to evaluate atogepant effectiveness and tolerability as preventive 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 take atogepant 60 mg daily for at least 12 weeks up to two years, according to effectiveness, tolerability and eventual approval of reimbursability criteria.

Data will be collected at baseline and every three months for two years. Subjects will be asked to keep a headache diary to collect monthly headache and migraine days, migraine severity, associated symptoms and drug consumption. Questionnaires will be collected every three months.

Data collection will focus on: i) demographic data, ii) migraine history, iii) pain intensity, iv) presence and evolution of migraine associated symptoms and aura, v) migraine associated disability, vi) tolerability and eventual treatment- emergent adverse events, vii) treatment persistence. The online database REDCap will be used for data collection.

• Study Type: Observational
• Enrollment (Actual): 500

Contacts and Locations

Study Locations

• Italy
  • Florence, Italy, 50134
    • SOD Centro Cefalee e Farmacologia Clinica, AOU Careggi
  • Roma, Italy, 00128
    • Fondazione Policlinico Campus Bio-Medico

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 atogepant use for migraine preventive treatment.

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 monthly migraine days;
• 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
Chronic migraine; Patients affected by chronic migraine (> 15 monthly headache days with at least 8 days with migraine features) according to ICHD-III criteria.	Drug: Atogepant 60 mg; Patients using atogepant 60 mg tablet daily as migraine prevention
Episodic migraine; Patients affected by migraine with an episodic pattern (< 15 monthly migraine days) with or without aura according to ICHD-III criteria.	Drug: Atogepant 60 mg; Patients using atogepant 60 mg tablet daily as migraine prevention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in migraine frequency after three months of treatment	Changes in monthly migraine days after three months of treatment with atogepant compared to baseline (continuous variable)	Baseline (T0) - 3 months of treatment with atogepant (T3)
50% Response after three months of treatment	Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) after three months of treatment with atogepant (continuous variable)	Baseline (T0) - 3 months of treatment with atogepant (T3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in migraine frequency across twelve months of atogepant treatment	Changes in monthly migraine days after six and twelve months of treatment with atogepant compared to baseline (continuous variable)	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) across twelve months of treatment with atogepant	Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) after six and twelve months of treatment with atogepant (continuous variable)	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Evaluation of any adverse event (qualitative)	Type of any adverse events in patients receiving atogepant during the observation period (categorical variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Evaluation of any adverse event (quantitative)	Percentage of reported adverse events in patients receiving atogepant assessed quarterly during the observation period (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Evaluation of serious adverse event	Percentage of serious adverse events (namely those resulting in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect) in patients receiving atogepant during the observation period (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Evaluation of adverse event leading to treatment discontinuation	Percentage of adverse events leading to treatment discontinuation in patients receiving atogepant during the observation period (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Consistency of treatment response	Percentage of patients with a stable 50% response across twelve months of atogepant treatment (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in migraine disability (MIDAS)	Changes in MIgraine Disability ASsement questionnaire across treatment (continuous variable, 0-270 scale, higher scores indicate higher disability: 0-5, little/no disability; 6-10, mild disability; 11-20, moderate disability; >20, severe disability)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in migraine disability (HIT-6)	Changes in Headache Impact Test-6 questionnaire across treatment (continuous variable, 36-78 scale, higher scores indicates greater disability)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in response to acute migraine treatment (m-TOQ)	Changes in migraine Treatment Optimization Questionnaire across treatment (continuous variable, 0-8 scale, higher score indicates higher acute therapy effectiveness)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in allodynia (ASC-12)	Changes in Allodynia Symptoms Checklist-12 questionnaire across treatment (continuous variable, 0-24 scale, higher score indicates more severe allodynia)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in quality of life across atogepant treatment (MSQ)	Changes in Migraine Specific Quality of life questionnaire across treatment (continuous variable, 0-100 scale, 100 indicates full functionality)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in interictal burden across atogepant treatment (MIBS-4)	Changes in Migraine Interictal Burden Scale-4 questionnaire across treatment (continuous variable, 0-4 scale, 0 indicates no interictal burden, 1-2 mild level of interictal burden, 3 moderate interictal burden, 4 severe interictal burden)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Self-reported treatment effectiveness	Changes in Migraine Assessment of Current Therapy (Migraine-ACT) a 4-item questionnaire about treatment effectiveness and daily life repercussions, across treatment compared to baseline (continuous variable, 0-4 scale, higher scores indicates higher acute treatment effectiveness)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Percentage of patients with Medication overuse headache reverted during treatment	Percentage of patients with a baseline diagnosis of MOH reverted after 3 - 6 and 12 months of treatment (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the number of monthly migraine days with aura (quantitative)	Changes in monthly migraine days with aura across treatment (continuous variable, through headache diary assessment)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Variation of duration of aura (qualitative)	Changes in duration of aura across atogepant treatment (continuous variable - minutes, assessed through headache diary)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Variation of type of aura (qualitative)	Changes in type of aura across atogepant treatment (qualitative variable - assessed through headache diary and anamnestic data collection)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
MMDs reduction in patients Non-responders to mAbs	Change of monthly migraine days across treatment in those patients who did not respond to anti-CGRP mAbs (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Percentage of 50% Responders across treatment in patients Non-responders to mAbs	Percentage of 50% Responders across treatment in those patients who did not respond to anti-CGRP mAbs (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Menstrually-related migraine	Change in the number of menstrually-related attacks (according to ICHD-3) across treatment compared to baseline (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Change in self-reported effectiveness of treatment	Change in Patients Global Impression of Change (PGIC) questionnaire across treatment (continuous variable, scale 0-7, 1 very much improved, 2 much improved, 3 minimally improved, 4 no change, 5 minimally worse, 6 much worse, 7 very much worse)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in migraine severity	Changes in migraine severity (continuous variable, 0-10 numerical rating scale, higher scores indicate higher severity)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in migraine duration	Changes in migraine duration (continuous variable- hours- assessed through a paper diary)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in duration of the most bothersome symptom(s)	Changes in duration of the most bothersome symptom(s) across treatment (continuous variable, minutes, assessed through a paper diary)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Changes in severity of the most bothersome symptom(s)	Changes in severity of the most bothersome symptom(s) across treatment (continuous variable: 0-10 scale, higher scores indicate higher severity )	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

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; Ospedale Santo Stefano; Azienda Ospedaliero Universitaria Policlinico Modena; Fondazione Policlinico Universitario Campus Bio-Medico; A.O.U. Città della Salute e della Scienza; Euganea Health Unit, Padua, Italy; 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

• Schwedt TJ, Lipton RB, Ailani J, Silberstein SD, Tassorelli C, Guo H, Lu K, Dabruzzo B, Miceli R, Severt L, Finnegan M, Trugman JM. Time course of efficacy of atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial. Cephalalgia. 2022 Jan;42(1):3-11. doi: 10.1177/03331024211042385. Epub 2021 Sep 14.
• Tassorelli C, Nagy K, Pozo-Rosich P, Lanteri-Minet M, Sacco S, Nezadal T, Guo H, De Abreu Ferreira R, Forero G, Trugman JM. Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial. Lancet Neurol. 2024 Apr;23(4):382-392. doi: 10.1016/S1474-4422(24)00025-5. Epub 2024 Feb 13.
• Pozo-Rosich P, Ailani J, Ashina M, Goadsby PJ, Lipton RB, Reuter U, Guo H, Schwefel B, Lu K, Boinpally R, Miceli R, De Abreu Ferreira R, McCusker E, Yu SY, Severt L, Finnegan M, Trugman JM. Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Sep 2;402(10404):775-785. doi: 10.1016/S0140-6736(23)01049-8. Epub 2023 Jul 26.
• Goadsby PJ, Dodick DW, Ailani J, Trugman JM, Finnegan M, Lu K, Szegedi A. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial. Lancet Neurol. 2020 Sep;19(9):727-737. doi: 10.1016/S1474-4422(20)30234-9.
• Vernieri F, Iannone LF, Lo Castro F, Sebastianelli G, De Santis F, Corrado M, Marcosano M, Ornello R, Grazzi L, Montisano DA, De Cesaris F, Munafo A, Fofi L, Doretti A, Vaghi G, Pistoia F, Ferrandi D, Battistini S, Sacco S, Guerzoni S, Altamura C; Italian Headache Registry (RICe) Study Group. Effectiveness and tolerability of atogepant in the prevention of migraine: A real life, prospective, multicentric study (the STAR study). Cephalalgia. 2025 Apr;45(4):3331024251335927. doi: 10.1177/03331024251335927. Epub 2025 Apr 23.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2024
• Primary Completion (Actual): November 30, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: May 10, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 14, 2024

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; Migraine prevention; 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; atogepant
• Other Study ID Numbers: RICe_4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No