MedPath

Atogepant for Prophylaxis of Migraine in Participants Who Failed Previous Oral Prophylactic Treatments.

Phase 3
Completed
Conditions
Episodic Migraine
Interventions
Registration Number
NCT04740827
Lead Sponsor
Allergan
Brief Summary

This study will assess the safety, tolerability, and efficacy of Atogepant 60 mg compared with placebo in participants with episodic migraine and who have previously failed 2 to 4 classes of oral prophylactic treatments.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
315
Inclusion Criteria
  • At least a 1-year history of migraine with or without aura consistent with a diagnosis according to the ICHD-3, 2018.
  • Age of the participant at the time of migraine onset < 50 years -History of 4 to 14 migraine days per month on average in the 3 months prior to Visit 1 in the investigator's judgment
  • Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period.
  • 4 to 14 migraine days in the 28-day baseline period per eDiary
  • Failed oral migraine prophylaxis medications from 2 to 4 medication classes
Exclusion Criteria
  • Any clinically significant hematologic, endocrine, pulmonary, hepatic, gastrointestinal, or neurologic disease
  • Participant has any other concurrent pain condition that, in the opinion of the investigator, may significantly impact the current headache disorder
  • In the opinion of the investigator, confounding psychiatric conditions, dementia, epilepsy, or significant neurological disorders other than migraine
  • Has ≥ 15 headache days per month on average across the 3 months prior to Visit 1 in the investigator's judgment
  • Has ≥ 15 headache days in the 28-day baseline period per eDiary
  • Clinically significant cardiovascular or cerebrovascular disease
  • Has a history of migraine accompanied by diplopia or decreased level of consciousness or retinal migraine as defined by ICHD-3, 2018
  • Has a current diagnosis of chronic migraine, new persistent daily headache, medication overuse headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy as defined by ICHD-3, 2018

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants received atogepant-matching placebo tablets, orally, once daily (QD) for up to 12 weeks in a double-blind (DB) treatment period.
Atogepant 60 mgAtogepant 60 mgParticipants received atogepant 60 mg, orally, QD for up to 12 weeks in a DB treatment period.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Mean Monthly Migraine Days Across 12-Week Treatment Period in mITT PopulationBaseline to Week 12

Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache. The monthly (4-week) migraine days were defined as the total number of reported migraine days in diary divided by total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of migraine days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. Mixed-effects model for repeated measures (MMRM) was used for analysis.

Change From Baseline in Mean Monthly Migraine Days Across 12-Week Treatment Period in OTHE PopulationBaseline to Week 12

Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache. The monthly (4-week) migraine days were defined as the total number of reported migraine days in diary divided by total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of migraine days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. MMRM was used for analysis.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Mean Monthly Acute Medication Use Days Across the 12-week Treatment Period in mITT PopulationBaseline to Week 12

An acute medication use day is defined as any day on which a participant reports, per eDiary, the intake of allowed medication(s) to treat an acute migraine. The monthly (4-week) acute medication use days were defined as the total number of reported acute medication use days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of migraine days during the last 28 days prior to the randomization date. A negative change from Baseline indicates improvement.

Number of Participants With At Least a 50% Reduction in 3-Month Average of Monthly Migraine Days Across the 12-week Treatment Period in OTHE PopulationBaseline to Week 12

Data is reported for 50% responders averaged at each 4-week period. 50% responders are participants with at least a 50% reduction from baseline in 3-month average of monthly migraine days. Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache. The monthly (4-week) migraine days are equal to total number of reported migraine days in diary divided by total number of days with diary records in each 4-week period multiplied by 28.

Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)From first dose of study drug until 30 days after last dose of study drug (up to Week 12)

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. TEAEs were defined as any AE with the onset that was after the first dose of study intervention.

Change From Baseline in Mean Monthly Headache Days Across the 12-week Treatment Period in mITT PopulationBaseline to Week 12

Participants recorded daily total duration of a headache in a diary. A headache day is any calendar day on which the participant experienced a headache pain lasting 2 hours or longer unless an acute headache medication was used after the start of the headache. The monthly (4-week) headache days were defined as the total number of reported headache days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of headache days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. MMRM was used for analysis.

Number of Participants With At Least a 50% Reduction in 3-Month Average of Monthly Migraine Days Across the 12-week Treatment Period in mITT PopulationBaseline to Week 12

Data is reported for 50% responders averaged at each 4-week period. 50% responders are participants with at least a 50% reduction from baseline in 3-month average of monthly migraine days. Participants recorded daily duration of migraine in a diary. A migraine day was any calendar day on which the participant experienced a migraine headache. The monthly (4-week) migraine days are equal to total number of reported migraine days in diary divided by total number of days with diary records in each 4-week period multiplied by 28.

Change From Baseline in Mean Monthly Headache Days Across the 12-week Treatment Period in OTHE PopulationBaseline to Week 12

Participants recorded daily total duration of a headache in a diary. A headache day is any calendar day on which the participant experienced a headache pain lasting 2 hours or longer unless an acute headache medication was used after the start of the headache. The monthly (4-week) headache days were defined as the total number of reported headache days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of headache days during the last 28 days prior to the randomization date. Negative change from Baseline indicates improvement. MMRM was used for analysis.

Change From Baseline in Mean Monthly Acute Medication Use Days Across the 12-week Treatment Period in OTHE PopulationBaseline to Week 12

An acute medication use day is defined as any day on which a participant reports, per eDiary, the intake of allowed medication(s) to treat an acute migraine. The monthly (4-week) acute medication use days were defined as the total number of reported acute medication use days in the diary divided by the total number of days with diary records during each 4-week period and multiplied by 28. Each 4-week period was averaged. Baseline is defined as the number of migraine days during the last 28 days prior to the randomization date. A negative change from Baseline indicates improvement.

Change From Baseline in Migraine Specific Quality of Life Questionnaire (MSQ) v2.1 Role Function-Restrictive Domain Score at Week 12 in mITT PopulationBaseline to Week 12

The MSQ v2.1 is a 14-item questionnaire designed to measure health-related quality of life impairments attributed to migraine in the past 4 weeks. It is divided into 3 domains: Role Function Restrictive (question numbers 1-7, score ranges 7 to 42) assesses how migraines limit one's daily social and work-related activities; Role Function Preventive (question numbers 8-11, score ranges 4 to 24) assesses how migraines prevent these activities; and the Emotional Function (question numbers 12-14, score ranges 3 to 18) domain assesses the emotions associated with migraines. Participants respond to items using a 6-point scale ranging from none of the time to all of the time. Raw dimension scores are computed as a sum of item responses and rescaled to a 0 to 100 scale, where higher scores indicate better quality of life. MMRM was used for analysis.

Change From Baseline in Migraine Specific Quality of Life Questionnaire (MSQ) v2.1 Role Function-Restrictive Domain Score at Week 12 in OTHE PopulationBaseline to Week 12

The MSQ v2.1 is a 14-item questionnaire designed to measure health-related quality of life impairments attributed to migraine in the past 4 weeks. It is divided into 3 domains: Role Function Restrictive (question numbers 1-7, score ranges 7 to 42) assesses how migraines limit one's daily social and work-related activities; Role Function Preventive (question numbers 8-11, score ranges 4 to 24) assesses how migraines prevent these activities; and the Emotional Function (question numbers 12-14, score ranges 3 to 18) domain assesses the emotions associated with migraines. Participants respond to items using a 6-point scale ranging from none of the time to all of the time. Raw dimension scores are computed as a sum of item responses and rescaled to a 0 to 100 scale, where higher scores indicate better quality of life. MMRM was used for analysis.

Change From Baseline in Mean Monthly Physical Impairment Domain Score of the AIM-D Across the 12-Week Treatment Period in mITT PopulationBaseline to Week 12

The AIM-D is a 11-item PRO measure that assesses the impact of migraine on the performance of daily activities which includes 7 items: difficulty with household chores, errands, leisure activities at home, leisure or social activities outside the home, strenuous physical activities, concentrating, and thinking clearly and physical impairment; 4 items: difficulty walking, moving body, bending forward, moving head using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw physical impairment domain scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine (higher disease burden).

Change From Baseline in Mean Monthly Performance of Daily Activities Domain Score of the Activity Impairment in Migraine - Diary (AIM-D) Across the 12-Week Treatment Period in mITT PopulationBaseline to Week 12

The AIM-D is a 11-item patient-reported outcome (PRO) measure that assesses the impact of migraine on the performance of daily activities which include, 7 items: difficulty with household chores, errands, leisure activities at home, leisure or social activities outside the home, strenuous physical activities, concentrating, and thinking clearly and physical impairment; 4 items: difficulty walking, moving body, bending forward, moving head using a 6-point rating scale where 0=not difficult at all, 1=a little difficult, 2=somewhat difficult, 3=very difficult, 4=extremely difficult, and 5=I could not do it at all. The raw performance of daily activities domain scores were transformed to 0-100 scale, with higher scores indicating greater impact of migraine (higher disease burden).

Change From Baseline in the Headache Impact Test (HIT-6) Total Score at Week 12 in OTHE PopulationBaseline to Week 12

HIT-6 is a 6-question assessment used to measure the impact headaches have on a participant's ability to function on the job, at school, at home, and in social situations. It assesses the effect that headaches have on normal daily life and the participant's ability to function. Responses are based on frequency using a 5-point scale ranging from "never" to "always." The HIT-6 total score, which ranges from 36 to 78, is the sum of the responses - each of which is assigned a score ranging from 6 points (never) to 13 points (always). MMRM was used for the analyses.

Trial Locations

Locations (114)

Allied Physicians - Fort Wayne Neurological Center /ID# 226350

🇺🇸

Fort Wayne, Indiana, United States

Clinvest Research LLC /ID# 226273

🇺🇸

Springfield, Missouri, United States

FutureSearch Trials of Dallas, LP /ID# 226493

🇺🇸

Dallas, Texas, United States

Methodist Physicians Clinic /ID# 226470

🇺🇸

Fremont, Nebraska, United States

AmBeNet GmbH /ID# 226213

🇩🇪

Leipzig, Germany

INEP medical s.r.o. /ID# 226531

🇨🇿

Praha, Czechia

Neuropoint GmbH /ID# 226377

🇩🇪

Ulm, Germany

ZorgSaam Zorggroep Zeeuws-Vlaanderen /ID# 226317

🇳🇱

Terneuzen, Netherlands

Azienda Ospedaliero Universitaria Careggi /ID# 226502

🇮🇹

Florence, Italy

AOU Universita degli Studi della Campania Luigi Vanvitelli /ID# 226503

🇮🇹

Napoli, Italy

CHU de SAINT ETIENNE - Hopital Nord /ID# 226397

🇫🇷

St. Priest En Jarez, Loire, France

Amici Clinical Research - Raritan /ID# 226282

🇺🇸

Raritan, New Jersey, United States

Alfred Health /ID# 226341

🇦🇺

Melbourne, Victoria, Australia

Velocity Clinical Research - Boise /ID# 226320

🇺🇸

Meridian, Idaho, United States

The Royal Melbourne Hospital /ID# 226402

🇦🇺

Parkville, Victoria, Australia

Centrum Medyczne Oporow /ID# 226469

🇵🇱

Wroclaw, Dolnoslaskie, Poland

NZOZ Vitamed /ID# 226293

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Bydgoszcz, Kujawsko-pomorskie, Poland

Diex Recherche Sherbrooke Inc. /ID# 226375

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Sherbrooke, Quebec, Canada

Canisius-Wilhelmina Ziekenhuis /ID# 226488

🇳🇱

Nijmegen, Netherlands

CHU Nice - Hopital de Cimiez /ID# 226401

🇫🇷

Nice, Alpes-Maritimes, France

Valeomed Kft /ID# 226535

🇭🇺

Esztergom, Komarom-Esztergom, Hungary

Bugat Pal Korhaz /ID# 226357

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Gyöngyös, Heves, Hungary

Szent Borbala Korhaz /ID# 226400

🇭🇺

Tatabanya, Komarom-Esztergom, Hungary

Department of Neurology, University of Szeged /ID# 226442

🇭🇺

Szeged, Hungary

Centrum Medyczne Pratia Gdynia /ID# 226437

🇵🇱

Gdynia, Pomorskie, Poland

Mind Klinika Kft. /ID# 233438

🇭🇺

Budapest, Hungary

Sbhi Cp 2 Hdm /Id# 226494

🇷🇺

Moscow, Russian Federation

EuroMedis sp. z o.o. /ID# 226268

🇵🇱

Szczecin, Zachodniopomorskie, Poland

Silmedic Sp. z o.o. /ID# 226267

🇵🇱

Katowice, Slaskie, Poland

University Headache Clinic /ID# 226435

🇷🇺

Moscow, Russian Federation

Alpine Clinical Research Center /ID# 226201

🇺🇸

Boulder, Colorado, United States

Pharmacology Research Institute (PRI) - Encino (Wake) /ID# 226434

🇺🇸

Encino, California, United States

Pharmacology Research Institute (PRI) - Los Alamitos (Wake) /ID# 226388

🇺🇸

Los Alamitos, California, United States

Pharmacology Research Institute (PRI) - Los Alamitos (Wake) /ID# 226405

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Los Alamitos, California, United States

Excell Research, Inc /ID# 228386

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Oceanside, California, United States

Meridien Research /ID# 226224

🇺🇸

Saint Petersburg, Florida, United States

Sensible Healthcare /ID# 226197

🇺🇸

Ocoee, Florida, United States

Axiom Research /ID# 226379

🇺🇸

Colton, California, United States

Meridien Research /ID# 226302

🇺🇸

Saint Petersburg, Florida, United States

Deaconess Clinic - Gateway Health Center /ID# 226481

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Newburgh, Indiana, United States

Pharmasite Research, Inc. /ID# 226445

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Baltimore, Maryland, United States

StudyMetrix Research /ID# 226297

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Saint Peters, Missouri, United States

Albuquerque Clinical Trials, Inc /ID# 233445

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Albuquerque, New Mexico, United States

FutureSearch Trials of Neurology /ID# 226423

🇺🇸

Austin, Texas, United States

CTI Clinical Trial and Consulting /ID# 226281

🇺🇸

Cincinnati, Ohio, United States

Austin Clinical Trial Partners /ID# 228387

🇺🇸

Austin, Texas, United States

DiscoveResearch, Inc /ID# 226491

🇺🇸

Bryan, Texas, United States

Aggarwal and Associates Limited /ID# 226321

🇨🇦

Brampton, Ontario, Canada

Highland Clinical Research /ID# 226288

🇺🇸

Salt Lake City, Utah, United States

Northwest Clinical Research Center /ID# 226228

🇺🇸

Bellevue, Washington, United States

LinQ Research, LLC /ID# 226227

🇺🇸

Pearland, Texas, United States

Ottawa Headache Centre Research Inc /ID# 226257

🇨🇦

Ottawa, Ontario, Canada

A-SHINE s.r.o. /ID# 226208

🇨🇿

Plzen, Czechia

POLIKLINIKA CHOCEN, a.s. /ID# 226510

🇨🇿

Chocen, Czechia

CCR Ostrava, s.r.o. /ID# 226279

🇨🇿

Ostrava, Czechia

BRAIN-SOULTHERAPY s.r.o. /ID# 226489

🇨🇿

Kladno, Czechia

CLINTRIAL s.r.o. /ID# 226192

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Prague 10, Czechia

DADO MEDICAL s.r.o. /ID# 226548

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Praha, Czechia

CCR Czech a.s /ID# 226270

🇨🇿

Prague 4, Czechia

FORBELI s.r.o. /ID# 226396

🇨🇿

Prague, Czechia

CHU Lille /ID# 226501

🇫🇷

Lille, Nord, France

Rigshospitalet Glostrup /ID# 226271

🇩🇰

Glostrup, Hovedstaden, Denmark

CCR Prague s.r.o. /ID# 226214

🇨🇿

Praha, Czechia

Vestra Clinics s.r.o. /ID# 226547

🇨🇿

Rychnov nad Kneznou, Czechia

NeuroMed Zlin s.r.o. /ID# 226487

🇨🇿

Zlin, Czechia

CHU Clermont Ferand - Hopital Gabriel Montpied /ID# 226438

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Clermont Ferrand, France

AP-HP - Hopital Lariboisière /ID# 226221

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Paris, France

Universitaetsklinikum Tuebingen /ID# 226529

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Tubingen, Baden-Wuerttemberg, Germany

Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 226441

🇩🇪

Berlin, Germany

Klinische Forschung Hannover-Mitte GmbH /ID# 226195

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Hannover, Germany

Universitaetsklinikum Essen /ID# 226527

🇩🇪

Essen, Germany

Klinische Forschung Dresden GmbH /ID# 226194

🇩🇪

Dresden, Germany

Praxis Dr. Gendolla /ID# 226497

🇩🇪

Essen, Germany

Universitaetsklinikum Jena Klinik fuer Neurologie /ID# 226439

🇩🇪

Jena, Germany

Vitos Orthopaedische Klinik Kassel gemeinnuetzige GmbH /ID# 231767

🇩🇪

Kassel, Germany

Schmerzklinik Kiel /ID# 226499

🇩🇪

Kiel, Germany

Universitaetsmedizin Rostock /ID# 226517

🇩🇪

Rostock, Germany

Pharmakologisches Studienzentrum Chemnitz GmbH /ID# 226202

🇩🇪

Mittweida, Germany

Neuropraxis Muenchen Sued /ID# 226216

🇩🇪

Unterhaching, Germany

Intermed GmbH /ID# 226376

🇩🇪

Wiesbaden, Germany

Studienzentrum Nord-West /ID# 226360

🇩🇪

Westerstede, Germany

DKD Helios Klinik Wiesbaden /ID# 226534

🇩🇪

Wiesbaden, Germany

Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 226485

🇭🇺

Kaposvár, Somogy, Hungary

Clinexpert Kft /ID# 226467

🇭🇺

Budapest, Hungary

Ospedale Ss. Filippo e Nicola /ID# 226530

🇮🇹

Avezzano, L Aquila, Italy

Univ. of Bologna-IRCCS-Istituto delle Scienze Neurologiche /ID# 226475

🇮🇹

Bologna, Italy

Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 226399

🇮🇹

Milan, Italy

Universita di Pavia /ID# 226536

🇮🇹

Pavia, Italy

Martini Ziekenhuis /ID# 226343

🇳🇱

Groningen, Netherlands

Gabinet Lekarski Jacek Rozniecki /ID# 226323

🇵🇱

Lodz, Lodzkie, Poland

Indywidualna Praktyka Lekarska dr hab. med. Anna Szczepanska-Szerej /ID# 226235

🇵🇱

Lublin, Lubelskie, Poland

Specjalistyczne Gabinety Sp. z o.o. /ID# 226266

🇵🇱

Krakow, Malopolskie, Poland

Duplicate_RCMed Oddzial Sochaczew /ID# 226369

🇵🇱

Sochaczew, Mazowieckie, Poland

Centrum Leczenia Padaczki i Migreny /ID# 226543

🇵🇱

Krakow, Malopolskie, Poland

Solumed Centrum Medyczne /ID# 226299

🇵🇱

Poznan, Wielkopolskie, Poland

Kazan State Medical University /ID# 226498

🇷🇺

Kazan, Tatarstan, Respublika, Russian Federation

Bashkir State Medical University /ID# 226552

🇷🇺

Ufa, Bashkortostan, Respublika, Russian Federation

University Clinical Hospital of Valladolid /ID# 226528

🇪🇸

Valledolid, Castellon, Spain

Cephalgolog /ID# 226541

🇷🇺

Moscow, Russian Federation

Hospital Unversitario Marques de Valdecilla /ID# 226239

🇪🇸

Santander, Cantabria, Spain

Hospital Universitario Vall d'Hebron /ID# 226230

🇪🇸

Barcelona, Spain

Hospital Clinico Universitario San Carlos /ID# 226483

🇪🇸

Madrid, Spain

Hospital Santa Creu i Sant Pau /ID# 226550

🇪🇸

Barcelona, Spain

Hospital Clinico Universitario de Valencia /ID# 226472

🇪🇸

Valencia, Spain

Queen Elizabeth University Hospital /ID# 226492

🇬🇧

Glasgow, United Kingdom

Hospital Clinico Universitario Lozano Blesa /ID# 226395

🇪🇸

Zaragoza, Spain

Karolinska university hospital, Huddinge /ID# 226215

🇸🇪

Huddinge, Stockholms Lan, Sweden

Re:Cognition Health - Guildford /ID# 226539

🇬🇧

Guildford, United Kingdom

NHS Highland /ID# 226542

🇬🇧

Inverness, United Kingdom

King's College Hospital NHS Foundation Trust /ID# 226525

🇬🇧

London, United Kingdom

St Pancras Clinical Research /ID# 226551

🇬🇧

London, United Kingdom

Leeds Teaching Hospitals NHS Trust /ID# 226538

🇬🇧

Leeds, United Kingdom

Re:Cognition Health - London /ID# 226540

🇬🇧

London, United Kingdom

Fondazione Policlinico Universitario Campus Bio-Medico di Roma /ID# 226361

🇮🇹

Rome, Lazio, Italy

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