Last Update: Jul 17, 2023
A Randomized, Double-blind, Double-dummy, Parallel-group Study, Comparing the Efficacy and Safety of Remibrutinib Versus Teriflunomide in Participants With Relapsing Multiple Sclerosis, Followed by Extended Treatment With Open-label Remibrutinib
ClinicalTrials.gov Identifier:
Novartis Reference Number:CLOU064C12302
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis

The study CLOU064C12302 consists of an initial Core Part (CP) (maximum duration per participant of up to 30 months), followed by an Extension Part (EP, of up to 5 years duration) for eligible participants.

The Core Part is a randomized, double-blind, double-dummy, active comparator-controlled, fixed-dose, parallel-group, multi-center study in approximately 800 participants with relapsing multiple sclerosis (RMS).

The Extension Part is an open-label, single-arm, fixed-dose design in which eligible participants are treated with remibrutinib for up to 5 years.

A second study of identical design (CLOU064C12301) will be conducted simultaneously. Both studies will be conducted globally and data from the two studies will be pooled for some of the endpoints.

Relapsing Multiple Sclerosis
Phase 3
Recruiting
800
Dec 13, 2021
Oct 30, 2030
All
18 Years - 55 Years (Adult)

Interventions

Drug

Remibrutinib

tablet taken orally
Drug

Teriflunomide

capsule taken orally

Eligibility Criteria

Inclusion Criteria:

18 to 55 years of age
Diagnosis of RMS according to the 2017 McDonald diagnostic criteria
At least: 1 documented relapse within the previous year. OR 2 documented relapses within the previous 2 years, OR 1 active Gadolinium (Gd)-enhancing lesion in the 12 months.
EDSS score of 0 to 5.5 (inclusive)
Neurologically stable within 1 month

Exclusion Criteria:

Diagnosis of primary progressive multiple sclerosis (PPMS)
Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening
History of clinically significant CNS disease other than MS
Ongoing substance abuse (drug or alcohol)
History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer),
Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML
suicidal ideation or behavior
Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary , renal, hepatic, endocrine, metabolic, hematological disorders or gastrointestinal disease that can interfere with interpretation of the study results or protocol adherence
Participants who have had a splenectomy
Active clinically significant systemic bacterial, viral, parasitic or fungal infections
Positive results for syphilis or tuberculosis testing
Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
Active, chronic disease of the immune system (including stable disease treated with immune therapy (e.g. Leflunomide, Methotrexate)) other than MS (e.g. rheumatoid arthritis, systemic lupus erythematosus, etc.) with the exception of well-controlled diabetes or thyroid disorder.
Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody
History or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or participants with moderate or severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary disease.
History of severe renal disease or creatinine level
Participants at risk of developing or having reactivation of hepatitis

Hematology parameters at screening:

Hemoglobin: < 10 g/dl (<100g/L)
Platelets: < 100000/mm3 (<100 x 109/L)
Absolute lymphocyte count < 800/mm3 (<0.8 x 109/L)
White blood cells: <3 000/mm3 (<3.0 x 109/L)
Neutrophils: < 1 500/mm3 (<1.5 x 109/L)
B-cell count < 50% lower limit of normal (LLN) or total IgG & total IgM < LLN (only required for participants who had a history of receiving B-cell therapies, such as rituximab, ocrelizumab or ofatumumab, prior to screening)
History or current diagnosis of significant ECG abnormalities
Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment (prior to randomization)
Use of other investigational drugs
Requirement for anticoagulant medication or use of dual anti-platelet therapy Significant bleeding risk or coagulation disorders,
History of gastrointestinal bleeding
Major surgery within 8 weeks prior to screening
History of hypersensitivity to any of the study drugs or excipients
Pregnant or nursing (lactating) female participants, prior to randomization
Women of childbearing potential not using highly effective contraception
Sexually active males not agreeing to use condom
Have received any live or live-attenuated vaccines within 6 weeks of randomization or requirement to receive these vaccinations during study
Use of strong CYP3A4 inhibitors or use of moderate or strong CYP3A4 inducers within two weeks prior to randomization

Inclusion to Extension part:

• patient who complete the Core Part of the study on double-blind study treatment and conduct the Accelerated Elimination Procedure (AEP)

Other inclusion and exclusion criteria may apply

Study Location

Novartis Investigative Site

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Rosario,Santa Fe,S2000BZL,Argentina

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Bombal,Mendoza,M5500DXO,Argentina

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San Miguel De,Tucuman,T4000,Argentina

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Buenos Aires,C1012AAR,Argentina

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Porto Alegre,Rio Grande Do Sul,90035-001,Brazil

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Porto Alegre,RS,90110-000,Brazil

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Vitoria,ES,29055-450,Brazil

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Joinville,Santa Catarina,89202-165,Brazil

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Porto Alegre,RS,90430-001,Brazil

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Sao Paulo,01240-020,Brazil

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Brasilia,DF,70200-730,Brazil

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Curitiba,PR,81210-310,Brazil

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Sofia,1309,Bulgaria

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Sofia,1407,Bulgaria

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Sofia,1413,Bulgaria

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Plovdiv,4002,Bulgaria

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Halifax,Nova Scotia,B3H 4K4,Canada

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Edmonton,Alberta,T6G 2B7,Canada

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Greenfield Park,Quebec,J4V 2J2,Canada

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Ottawa,Ontario,K1H 8L6,Canada

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Levis,Quebec,G6W 0M5,Canada

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Wuhan,Hubei,430060,China

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Yinchuan,Ningxia,100039,China

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Shanghai,200025,China

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Shanghai,200040,China

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Wenzhou,Zhejiang,325000,China

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Taiyuan,Shanxi,030001,China

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Fuzhou,Fujian,350025,China

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Hangzhou,Zhejiang,310006,China

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Hangzhou,Zhejiang,310016,China

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Nanjing,Jiangsu,210029,China

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Wuhan,Hubei,430030,China

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Vukovar,32000,Croatia

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Split,HRV,21000,Croatia

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Zagreb,10000,Croatia

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Varazdin,HRV,42000,Croatia

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Tallinn,11315,Estonia

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Tartu,51014,Estonia

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Nantes,Cedex 1,44093,France

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Lille Cedex,59037,France

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Dijon,21034,France

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Suresnes,92150,France

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Lille,59000,France

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CAEN Cedex,14033,France

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Contamine Sur Arve,74130,France

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Toulon Cedex 9,Val De Marne,83800,France

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Clermont-Ferrand Cedex 1,63003,France

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Toulouse Cedex 9,31059,France

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Grenoble,38042,France

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Nice Cedex,06202,France

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Nimes,30029,France

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Gonesse,95500,France

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Thessaloniki,GR 54636,Greece

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Amyntaio,53246,Greece

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Athens,Attica,11526,Greece

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Athens,115 28,Greece

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Larissa,GR,411 10,Greece

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Ioannina,GR,455 00,Greece

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Athens,12462,Greece

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Amritsar,Punjab,143006,India

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Hyderabad,Telangana,500082,India

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New Delhi,Delhi,110 060,India

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Lucknow,Uttar Pradesh,226007,India

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Kolkata,West Bengal,700017,India

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Pune,Maharashtra,411013,India

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Orbassano,TO,10043,Italy

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Napoli,80131,Italy

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Modena,MO,41126,Italy

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Firenze,FI,50134,Italy

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Pozzilli,IS,86077,Italy

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Foggia,FG,71100,Italy

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Brindisi,BR,72100,Italy

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Messina,ME,98121,Italy

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Pavia,PV,27100,Italy

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Suita,Osaka,565 0871,Japan

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Koriyama city,Fukushima,963-8052,Japan

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Fukuoka city,Fukuoka,812-8582,Japan

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Fukuoka,810-0022,Japan

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Kyoto-city,Kyoto,616-8255,Japan

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Kobe-shi,Hyogo,650-0017,Japan

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Moriguchi,Osaka,570-8507,Japan

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Sapporo city,Hokkaido,063-0005,Japan

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Nagoya,Aichi,466 8560,Japan

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Kashihara city,Nara,634 8522,Japan

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Isehara,Kanagawa,259-1193,Japan

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Shinjuku-ku,Tokyo,160 8582,Japan

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Kodaira,Tokyo,187-8551,Japan

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Chiba,260 8677,Japan

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Shinjuku-ku,Tokyo,160-0023,Japan

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Niigata,951 8520,Japan

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Nishinomiya,Hyogo,663 8501,Japan

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Sendai city,Miyagi,983 8512,Japan

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Chihuahua,31203,Mexico

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Queretaro,76070,Mexico

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Ciudad de Mexico,Distrito Federal,06700,Mexico

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Ciudad De Mexico,14050,Mexico

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Katowice,40-123,Poland

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Krakow,31-637,Poland

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Zabrze,41-800,Poland

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Bialystok,15-704,Poland

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Plewiska,Poznan,62-064,Poland

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Wroclaw,51-685,Poland

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Katowice,40 571,Poland

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Santa Maria da Feira,4520 211,Portugal

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Lisboa,1600190,Portugal

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Braga,4710243,Portugal

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Matosinhos,Porto,4454509,Portugal

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Leiria,2410-104,Portugal

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Guaynabo,00968,Puerto Rico

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Constanta,900591,Romania

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Constanta,ROM,900123,Romania

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Campulung Muscel,ROM,115100,Romania

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Targu Mures,540136,Romania

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Banska Bystrica,975 17,Slovakia

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Bratislava,83305,Slovakia

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Banska Bystrica,974 04,Slovakia

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Maribor,2000,Slovenia

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Ljubljana,1000,Slovenia

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Celje,3000,Slovenia

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Rosebank,2196,South Africa

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Bloemfontein,Free State,9301,South Africa

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Pretoria,0041,South Africa

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Vitoria-Gasteiz,País Vasco,01009,Spain

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Madrid,28040,Spain

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Sevilla,Andalucia,41009,Spain

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Torrejon de Ardoz,Madrid,28850,Spain

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Barcelona,Catalunya,08003,Spain

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Santiago de Compostela,Galicia,15706,Spain

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Valencia,Comunidad Valenciana,46017,Spain

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Pozuelo de Alarcon,Madrid,28223,Spain

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Valencia,46026,Spain

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Gijon,Asturias,33394,Spain

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Hospitalet de Llobregat,Barcelona,08907,Spain

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Madrid,28009,Spain

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Stockholm,102 35,Sweden

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Stockholm,141 86,Sweden

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Sancaktepe,Istanbul,34785,Turkey

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Izmir,35620,Turkey

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Bursa,16140,Turkey

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Kayseri,38280,Turkey

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Pendik Istanbul,34899,Turkey

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Samsun,55139,Turkey

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Kocaeli,41380,Turkey

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Istanbul,34093,Turkey

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London,W1G 9JF,United Kingdom

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Boston,Massachusetts,02111,United States

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Frisco,Texas,75035,United States

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Pembroke Pines,Florida,33024,United States

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Miami,Florida,33136,United States

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Houston,Texas,77094,United States

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Green Bay,Wisconsin,54311,United States

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Naples,Florida,34102,United States

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Bradenton,Florida,34209,United States

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Milwaukee,Wisconsin,53226,United States

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Maitland,Florida,32751,United States

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Orlando,Florida,32803,United States

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Knoxville,Tennessee,37922,United States

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Suwanee,Georgia,30024,United States

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Hanford,California,93230,United States

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Pensacola,Florida,32514,United States

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Kansas City,Kansas,66160,United States

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El Paso,Texas,79935,United States

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Greer,South Carolina,29650,United States

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Indian Land,South Carolina,29707,United States

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Crab Orchard,West Virginia,25827,United States

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Kansas City,Missouri,64128,United States

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Sherman,Texas,75092,United States

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Owosso,Michigan,48867,United States

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New Orleans,Louisiana,70121,United States

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Winter Park,Florida,32789,United States

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Gainesville,Florida,32610,United States

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Colorado Springs,Colorado,80907,United States

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Boca Raton,Florida,33487,United States

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San Antonio,Texas,78229,United States

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Merrillville,Indiana,46410,United States

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Patchogue,New York,11772,United States

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Charlotte,North Carolina,28210,United States

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Aurora,Colorado,80045,United States

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Dayton,Ohio,45408,United States

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Hollywood,Florida,33021,United States

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Seattle,Washington,98133,United States

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Vero Beach,Florida,32960,United States

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Port Orange,Florida,32127,United States

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Columbus,Ohio,43235,United States

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Frederick,Maryland,21702,United States

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Denver,Colorado,80210,United States

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