A Study to Compare the Safety and Efficacy of an Aromatase Inhibitor in Combination With Lapatinib, Trastuzumab or Both for the Treatment of Hormone Receptor Positive, HER2+ Metastatic Breast Cancer

A Phase III Trial to Compare the Safety and Efficacy of Lapatinib Plus Trastuzumab Plus an Aromatase Inhibitor (AI) vs. Trastuzumab Plus an AI vs. Lapatinib Plus an AI as 1st- or 2nd- Line Therapy in Postmenopausal Subjects With Hormone Receptor+, HER2-positive Metastatic Breast Cancer (MBC) Who Received Prior Trastuzumab and Endocrine Therapies

ClinicalTrials.gov Identifier: NCT01160211

Novartis Reference Number: 114299

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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

A study to compare the safety and efficacy of an aromatase inhibitor in combination with lapatinib, trastuzumab or both for the treatment of hormone receptor positive, HER2+ metastatic breast cancer (MBC).

Condition 
Neoplasms, Breast
Phase 
Phase 3
Overall status 
Active, not recruiting
Enrollment count 
369 participants
Start date 
May 05, 2011
Completion date 
May 05, 2021
Gender 
Female
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
lapatinib
1000 mg by mouth once a day
Drug
trastuzumab
Loading dose of 8 mg/kg IV followed by the maintenance dose of 6 mg/kg IV every 3 weeks
Drug
Aromatase inhibitor
Aromatase inhibitor (either letrozole, anastrozole, or exemestane) of investigator's choice given by mouth once daily
Drug
lapatinib
1500 mg by mouth once daily

Eligibility Criteria

Inclusion Criteria

Subjects eligible for enrollment in the study must meet all of the following criteria:

Signed written informed consent. In Korea and Japan, subjects between >=18 and <20 years of age must also have a legal representative sign the written informed consent.

Post-menopausal female subjects >=18 years of age. Post-menopausal as defined by any of the following:

Subjects at least 60 years of age.
Subjects under 60 years of age and amenorrhic for at least 12 consecutive months AND follicle-stimulating hormone (FSH) and estradiol levels in postmenopausal range (utilizing ranges from the local laboratory facility).
Prior bilateral oophorectomy.
Prior radiation castration with amenorrhea for at least 6 months
Subjects must have a history of histologically confirmed breast cancer, with a clinically confirmed diagnosis of metastatic disease [confirmed by histology, cytology or other clinical means (e.g. CT, MRI)]. Subjects may have either measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Tumors that are ER+ and/or PgR+ by local laboratory

Documentation of HER2 overexpression or gene amplification, in the invasive component of either the primary tumor or metastatic disease site as defined as:

3+ by Immunohistochemistry (IHC) and/or
HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of ≥2.0]

Subject must have received at least one prior regimen containing trastuzumab in combination with chemotherapy for breast cancer:.

Subject has ONLY received prior trastuzumab in combination with chemotherapy as neoadjuvant and/or adjuvant treatment. OR
Subject has received ONE prior trastuzumab-containing regimen for metastatic disease (and has progressed), and may or may not have received prior trastuzumab in combination with chemotherapy as neoadjuvant and/or adjuvant treatment.
Subject must have received prior endocrine therapy (such as aromatase inhibitors or selective estrogen receptor modulators). 8. Subjects who have a life expectancy of > 6 months as assessed by the treating investigator

9. Subjects must have baseline Left Ventricular Ejection Fraction (LVEF) ≥50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA) 10. Subject must have an ECOG performance status of 0-1 11. All prior treatment related toxicities must be CTCAE (Version 4.0) ≤ Grade 1 at the time of randomization 12. Completion of screening assessments 13. Adequate baseline organ function. 14. Subjects must meet all of the following criteria:

QTc <450msec or
QTc <480msec for subjects with bundle branch block The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB) or to Fridericia's formula (QTcF), machine or manual over read, for males and females. The specific formula that will be used in a protocol should be determined prior to initiation of the study, and the formula used to determine inclusion and discontinuation should be the same throughout the study. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period

Exclusion criteria:

History of another malignancy. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
Subjects with extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor, or the disease is considered by the investigator to be rapidly progressing or life threatening (subjects who are intended for chemotherapy)

Serious cardiac illness or medical condition including but not confined to:

Uncontrolled arrhythmias
Uncontrolled or symptomatic angina
History of congestive heart failure (CHF)
Documented myocardial infarction <6 months from study entry
Known history of, or clinical evidence of, central nervous system (CNS) metastases or leptomeningeal carcinomatosis
Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
Have a concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject's safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent)
Have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study agents or their excipients that, in the opinion of the Investigator or GSK medical monitor, contraindicates their participation
Any prohibited medication.
Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.

Study Locations

United States
Novartis Investigative Site
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La Jolla, 92093-0987
California
United States
Novartis Investigative Site
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Pleasant Hill, 94523
California
United States
Novartis Investigative Site
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Hollywood, 33021
Florida
United States
Novartis Investigative Site
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Miami, 33145
Florida
United States
Novartis Investigative Site
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Augusta, 30912
Georgia
United States
Novartis Investigative Site
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Lawrenceville, 30046
Georgia
United States
Novartis Investigative Site
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Chicago, 60611-2906
Illinois
United States
Novartis Investigative Site
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Goshen, 46526
Indiana
United States
Novartis Investigative Site
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Waterloo, 52132
Iowa
United States
Novartis Investigative Site
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Grand Rapids, 49503
Michigan
United States
Novartis Investigative Site
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Minneapolis, 55407-3799
Minnesota
United States
Novartis Investigative Site
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Billings, 59102
Montana
United States
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Omaha, 68114
Nebraska
United States
Novartis Investigative Site
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Albuquerque, 87106
New Mexico
United States
Novartis Investigative Site
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Albuquerque, 87110
New Mexico
United States
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Cary, 27518
North Carolina
United States
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Dayton, 45420
Ohio
United States
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Germantown, 38138
Tennessee
United States
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Houston, 77030
Texas
United States
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Tacoma, 98405
Washington
United States
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Milwaukee, 53226
Wisconsin
United States
Argentina
Novartis Investigative Site
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Berazategui, B1880BBF
Buenos Aires
Argentina
Novartis Investigative Site
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Capital Federal, C1417DTN
Buenos Aires
Argentina
Novartis Investigative Site
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Ciudad Aut6noma de Buenos Aires, C1050AAK
Buenos Aires
Argentina
Novartis Investigative Site
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Ciudad Autonoma de Buenos Aires, C1125ABD
Buenos Aires
Argentina
Novartis Investigative Site
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Ciudad Autonoma de Buenos Aires, C1280AEB
Buenos Aires
Argentina
Novartis Investigative Site
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La Plata, B1920CMK
Buenos Aires
Argentina
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Viedma, R8500ACE
Río Negro
Argentina
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Rosario, S2000KZE
Santa Fe
Argentina
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Ciudad Autonoma de Buenos Aires, C1025ABH
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Argentina
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Cordoba, X5004FHP
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Argentina
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La Rioja, F5300COE
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Argentina
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Quilmes, 1878
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Argentina
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San Miguel de Tucuman, T4000IAK
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Argentina
Australia
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Box Hill, 3128
Victoria
Australia
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Wodonga, 3690
Victoria
Australia
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Adelaide, 5000
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Australia
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Douglas, 4814
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Australia
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Ringwood East, 3135
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Australia
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Tweed Heads, 2485
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Australia
Belgium
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Leuven, 3000
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Belgium
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Liege, 4000
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Belgium
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Namur, 5000
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Belgium
Brazil
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Fortaleza, 60430-230
Ceará
Brazil
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Goiania, 74605-070
Goiás
Brazil
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Porto Alegre, 90470-340
Rio Grande Do Sul
Brazil
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Porto Alegre, 91350-200
Rio Grande Do Sul
Brazil
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Barretos, 14784-400
São Paulo
Brazil
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Sao Paulo, 01317-001
São Paulo
Brazil
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Sao Paulo, 01323-903
São Paulo
Brazil
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Sao Paulo, 03102-002
São Paulo
Brazil
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Sao Paulo, 05651-901
São Paulo
Brazil
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Rio de Janeiro, 20560-120
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Brazil
Bulgaria
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Plovdiv, 4004
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Bulgaria
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Sofia, 1330
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Bulgaria
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Sofia, 1756
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Bulgaria
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Sofia, 1784
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Bulgaria
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Varna, 9010
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Bulgaria
Canada
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Calgary, T2N 4N2
Alberta
Canada
China
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Fuzhou, 350001
Fujian
China
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Guangzhou, 510060
Guangdong
China
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Changchun, 130021
Jilin
China
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Harbin, 150081
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China
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Shanghai, 200032
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China
Colombia
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Monteria,
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Colombia
Croatia
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Osijek, 31000
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Croatia
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Pula, 52100
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Croatia
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Zagreb, 10000
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Croatia
France
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Besancon, 25030
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France
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Le Mans, 72000
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France
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Lille, 59000
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France
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Montpellier Cedex 5, 34298
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France
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Nancy, 54100
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France
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Paris Cedex 20, 75970
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France
Germany
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Heidelberg, 69115
Baden-Wuerttemberg
Germany
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Tuebingen, 72076
Baden-Wuerttemberg
Germany
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Muenchen, 80335
Bayern
Germany
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Muenchen, 81675
Bayern
Germany
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Regensburg, 93053
Bayern
Germany
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Rosenheim, 83022
Bayern
Germany
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Fuerstenwalde, 15517
Brandenburg
Germany
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Rostock, 18059
Mecklenburg-Vorpommern
Germany
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Goslar, 38642
Niedersachsen
Germany
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Hannover, 30559
Niedersachsen
Germany
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Aachen, 52066
Nordrhein-Westfalen
Germany
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Bottrop, 46236
Nordrhein-Westfalen
Germany
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Troisdorf, 53840
Nordrhein-Westfalen
Germany
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Velbert, 42551
Nordrhein-Westfalen
Germany
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Halle, 06120
Sachsen-Anhalt
Germany
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Kiel, 24103
Schleswig-Holstein
Germany
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Berlin, 10317
-
Germany
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Berlin, 12200
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Germany
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Hamburg, 20246
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Germany
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Hamburg, 22081
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Germany
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Hamburg, 22087
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Germany
Greece
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Athens, 115 28
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Greece
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Chania, 73100
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Greece
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Heraklion, 71110
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Greece
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Perioxi Dragana, Alexandroupolis, 68100
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Greece
Hong Kong
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Hong Kong,
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Hong Kong
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Kowloon,
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Hong Kong
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Pokfulam,
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Hong Kong
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Tuen Mun,
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Hong Kong
Hungary
Novartis Investigative Site
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Budapest, 1032
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Hungary
Novartis Investigative Site
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Budapest, 1125
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Hungary
Novartis Investigative Site
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Debrecen, H-4032
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Hungary
Novartis Investigative Site
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Gyor, H-9024
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Hungary
Novartis Investigative Site
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Gyula, 5700
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Hungary
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Kaposvar, 7400
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Hungary
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Miskolc, 3526
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Hungary
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Nyiregyhaza, 4400
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Hungary
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Pecs, 7624
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Hungary
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Szeged, 6720
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Hungary
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Szolnok, 5004
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Hungary
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Veszprem, 8200
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Hungary
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Zalaegerszeg, H-8900
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Hungary
India
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Bangalore, 560052
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India
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Chennai, 600116
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India
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Delhi, 110085
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India
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Nagpur, 440010
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India
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New Delhi, 110 092
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India
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Pune, 411001
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India
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Surat, Saroli - 394601Dist - Surat
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India
Ireland
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Dublin 7,
-
Ireland
Novartis Investigative Site
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Dublin, 4
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Ireland
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Dublin, 7
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Ireland
Novartis Investigative Site
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Dublin, 8
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Ireland
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Galway,
-
Ireland
Israel
Novartis Investigative Site
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Haifa, 31096
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Israel
Novartis Investigative Site
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Jerusalem, 91120
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Israel
Novartis Investigative Site
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Petah-Tikva, 49100
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Israel
Novartis Investigative Site
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Ramat Gan, 52621
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Israel
Novartis Investigative Site
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Rehovot, 76100
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Israel
Novartis Investigative Site
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Tel Aviv, 69710
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Israel
Italy
Novartis Investigative Site
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Parma, 43100
Emilia-Romagna
Italy
Novartis Investigative Site
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Piacenza, 29100
Emilia-Romagna
Italy
Novartis Investigative Site
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Monza, 20052
Lombardia
Italy
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Pavia, 27100
Lombardia
Italy
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Rozzano (MI), 20089
Lombardia
Italy
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San Giovanni Rotondo, 71013
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Italy
Japan
Novartis Investigative Site
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Aichi, 464-8681
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Japan
Novartis Investigative Site
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Chiba, 277-8577
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Japan
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Ehime, 791-0280
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Japan
Novartis Investigative Site
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Kagoshima, 892-0833
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Japan
Novartis Investigative Site
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Osaka, 540-0006
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Japan
Novartis Investigative Site
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Osaka, 565-0871
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Japan
Novartis Investigative Site
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Saitama, 350-1298
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Japan
Novartis Investigative Site
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Saitama, 362-0806
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Japan
Novartis Investigative Site
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Shizuoka, 411-8777
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Japan
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Tokyo, 104-8560
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Japan
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Tokyo, 113-8677
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Japan
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Tokyo, 142-8666
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Japan
Korea, Republic of
Novartis Investigative Site
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Gyeonggi-do, 10408
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Korea, Republic of
Novartis Investigative Site
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Seoul, 03080
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Korea, Republic of
Novartis Investigative Site
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Seoul, 06351
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Korea, Republic of
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Seoul, 138-736
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Korea, Republic of
Lithuania
Novartis Investigative Site
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Vilnius, LT-08660
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Lithuania
Norway
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Lorenskog,
-
Norway
Peru
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Miraflores, Lima 18
Lima
Peru
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San Borja, Lima 41
Lima
Peru
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San Isidro, Lima 27
Lima
Peru
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Arequipa,
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Peru
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Lima, Lima 18
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Peru
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Trujillo, 44
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Peru
Philippines
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Makati City, 1218
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Philippines
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Quezon City, 1102
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Philippines
Poland
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Konin, 62-500
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Poland
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Lubin, 59-301
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Poland
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Otwock, 05-400
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Poland
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Warszawa, 02-776
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Poland
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Warszawa, 04-125
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Poland
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Wieliszew, 05-135
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Poland
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Wroclaw, 53-413
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Poland
Portugal
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Coimbra, 3000-075
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Portugal
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Evora, 7000-811
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Portugal
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Lisboa, 1649-035
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Portugal
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Lisbon, 1400-038
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Portugal
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Porto, 4200-072
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Portugal
Puerto Rico
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San Juan, 00910
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Puerto Rico
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San Juan, 00935
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Puerto Rico
Romania
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Bucharest, 050098
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Romania
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Bucuresti, 022328
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Romania
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Timisoara, 300239
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Romania
Russian Federation
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Arkhangelsk, 163045
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Russian Federation
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Kazan, 420029
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Russian Federation
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Moscow, 115478
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Russian Federation
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Moscow, 117997
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Russian Federation
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Ryazan, 390011
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Russian Federation
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St. Petersburg, 197022
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Russian Federation
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St. Petersburg, 197758
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Russian Federation
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Tver, 170008
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Russian Federation
Serbia
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Belgrade, 11000
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Serbia
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Kragujevac, 34000
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Serbia
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Sremska Kamenica, 21204
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Serbia
Singapore
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Singapore, 308433
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Singapore
South Africa
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Cape Town, 7700
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South Africa
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Durban, 4091
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South Africa
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Port Elizabeth, 6045
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South Africa
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Pretoria, 0081
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South Africa
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Saxonwold, Johannesburg, 2196
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South Africa
Spain
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Barcelona, 08025
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Spain
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Barcelona, 08036
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Spain
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Castellon, 12002
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Spain
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Cordoba, 14004
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Spain
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La Coruna, 15009
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Spain
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Madrid, 28040
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Spain
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Santa Cruz de Tenerife, 38320
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Spain
Taiwan
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Changhua, 500
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Taiwan
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Kaohsiung Hsien, 833
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Taiwan
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Taipei City, 11217
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Taiwan
Turkey
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Ankara,
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Turkey
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Izmir, 35100
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Turkey
Ukraine
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Chernivtsi, 58013
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Ukraine
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Dnipropetrovsk, 49102
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Ukraine
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Kharkiv, 61070
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Ukraine
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Khmelnytskyi, 29000
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Ukraine
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Lyutizh, 07352
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Ukraine
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Sumy, 40005
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Ukraine
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Uzhgorod, 88000
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Ukraine
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Vinnitsia, 21029
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Ukraine
United Kingdom
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Chelmsford, CM1 7ET
Essex
United Kingdom
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Birmingham, B18 7QH
West Midlands
United Kingdom
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Huddersfield, HD3 3EA
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United Kingdom
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London, NW3 2QG
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United Kingdom
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London, SW3 6JJ
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United Kingdom
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Maidstone, ME16 9QQ
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United Kingdom
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Manchester, M20 4BX
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United Kingdom
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Nottingham, NG5 1PB
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United Kingdom
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Peterborough, PE3 9GZ
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United Kingdom
Novartis Investigative Site
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Sutton, SM2 5PT
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United Kingdom

Have a question?

Call 1-999-669-6682 or email [email protected]