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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02158936




Registration number
NCT02158936
Ethics application status
Date submitted
5/06/2014
Date registered
9/06/2014
Date last updated
12/12/2017

Titles & IDs
Public title
A Study of Eltrombopag or Placebo in Combination With Azacitidine in Subjects With International Prognostic Scoring System (IPSS) Intermediate-1, Intermediate-2 or High-risk Myelodysplastic Syndromes (MDS)
Scientific title
A Randomized, Double-blind, Placebo-controlled, Phase III, Multi-centre Study of Eltrombopag or Placebo in Combination With Azacitidine in Subjects With IPSS Intermediate-1, Intermediate 2 and High-risk Myelodysplastic Syndromes (MDS) SUPPORT: A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine
Secondary ID [1] 0 0
112121
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thrombocytopaenia 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eltrombopag
Treatment: Drugs - Azacitidine
Treatment: Drugs - Placebo
Treatment: Drugs - Placebo

Experimental: Eltrombopag - Eligible subject will receive a starting dose of eltrombopag of 200 milligrams (mg) (100 mg for subjects of East Asian heritage). Dose modifications of eltrombopag will be permitted by 100 mg increments (50 mg increments for East Asians) to a lowest dose of 100 mg (50 mg for East Asian heritage) or a maximum dose of 300 mg (150 mg for East Asian heritage) in order to maintain platelet counts at a safe and effective level (i.e. a level sufficient to avoid platelet transfusions and bleeding events). Subjects will receive azacitidine 75 mg/meter\^2 subcutaneously once daily for 7 days (+/- 3 day treatment window permitted) every 28 days, for at least 6 cycles if tolerated and until they are no longer receiving benefit (defined as at least stable disease per the investigator's assessment) or until disease progression, death, or unacceptable toxicity/adverse event. The subject may receive eltrombopag daily for the full 28 days each cycle for as long as the subject is receiving azacitidine

Placebo comparator: Placebo - Eligible subject will receive eltrombopag matching placebo. Subjects will receive azacitidine 75 mg/meter\^2 subcutaneously once daily for 7 days (+/- 3 day treatment window permitted) every 28 days, for at least 6 cycles if tolerated and until they are no longer receiving benefit (defined as at least stable disease per the investigator's assessment) or until disease progression, death, or unacceptable toxicity/adverse event. The subject may receive eltrombopag daily for the full 28 days each cycle for as long as the subject is receiving azacitidine


Treatment: Drugs: Eltrombopag
Eltrombopag will be round film-coated tablets containing eltrombopag equivalent to 50 mg (white to off-white), 200 mg and 300 mg (green) of eltrombopag free acid

Treatment: Drugs: Azacitidine
Subcutaneous Injection (IV if local standard)

Treatment: Drugs: Placebo
Eltrombopag matching placebo tablets

Treatment: Drugs: Placebo
Eltrombopag matching placebo tablets will be supplied
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Who Were Platelet Transfusion Independent During Cycles 1-4 of Azacitidine Therapy
Timepoint [1] 0 0
4 cycles (Cycle = 28 days)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Randomization until death or end of study, approximately 2 years
Secondary outcome [2] 0 0
Summary of Progression Free Survival From Investigator Assessment (ITT)
Timepoint [2] 0 0
First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Secondary outcome [3] 0 0
Summary of Progression Free Survival From Central Review (ITT)
Timepoint [3] 0 0
First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Secondary outcome [4] 0 0
Summary of AML Progression From Investigator Assessment and Central Review (ITT)
Timepoint [4] 0 0
First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Secondary outcome [5] 0 0
Best Disease Response From Investigator Assessment (ITT)
Timepoint [5] 0 0
At end of Cycle 6 (cycle=28 days) or end of therapy, whichever came first
Secondary outcome [6] 0 0
Best Disease Response From Central Review (ITT)
Timepoint [6] 0 0
At end of Cycle 6 (cycle=28 days) or end of therapy, whichever came first
Secondary outcome [7] 0 0
Hematologic Improvement (HI) in Platelets, Neutrophils, and Hemoglobin Based on the Modified IWG Criteria for MDS (ITT)
Timepoint [7] 0 0
From Day 1 to 4-week follow-up (samples collected weekly in Cycle 1, Days 1 and 15 in Cycles 2-6 and Day 1 of Cycles >=7)
Secondary outcome [8] 0 0
Number of Participants Who Were Platelet Transfusion Independent (ITT Set)
Timepoint [8] 0 0
From Day 1 to end of study treatment up to approximately 2 years
Secondary outcome [9] 0 0
Bleeding Adverse Events (AEs) >= Grade 3
Timepoint [9] 0 0
From Day 1 to 4-week follow-up up to approximately 2 years
Secondary outcome [10] 0 0
Number of of Subjects With Azacitidine Dose Delays, Dose Reductions, Interruptions
Timepoint [10] 0 0
From Day 1 to 4-week follow-up up to approximately 2 years
Secondary outcome [11] 0 0
Response Levels in All Domains of Euroquol-5 Dimensions of Health, 3 Response Levels (EQ-5D-3L™)
Timepoint [11] 0 0
From Day 1 to 4-week follow-up up to approximately 2 years
Secondary outcome [12] 0 0
Functional Assessment of Chronic Disease Therapy-fatigue Subscale (FACIT-Fatigue) (ITT)
Timepoint [12] 0 0
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Secondary outcome [13] 0 0
Medical Resource Utilization (MRU): Event -Hospitalizations Inpatient and Outpatient
Timepoint [13] 0 0
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Secondary outcome [14] 0 0
Medical Resource Utilization (MRU): Event and Use of Site Specific Medical Resources - Non-study Laboratory Tests
Timepoint [14] 0 0
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Secondary outcome [15] 0 0
Medical Resource Utilization (MRU): Use of Site Specific Medical Resources
Timepoint [15] 0 0
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Secondary outcome [16] 0 0
Summary of Post-Hoc Estimates of Steady-state Eltrombopag Cmax and Cmin Pharmacokinetic Parameters for a 50 mg Dose
Timepoint [16] 0 0
Cycle 1, Week 2: Pre-dose, 1.5 and 3 hour post dose; Cycle 1, Week 3: 4, 5.5, and 7 hours post dose
Secondary outcome [17] 0 0
Summary of Post-Hoc Estimates of Steady-state Eltrombopag AUC0 Infinity Pharmacokinetic Parameters for a 50 mg Dose
Timepoint [17] 0 0
Cycle 1, Week 2: Pre-dose, 1.5 and 3 hour post dose; Cycle 1, Week 3: 4, 5.5, and 7 hours post dose
Secondary outcome [18] 0 0
AUC0-infinity -Pharmacokinetic(s) Parameter of Azacitidine
Timepoint [18] 0 0
Cycle 2 Day 1: Pre-dose, 15 min, 0.5, 1, 2 and 4 hr post dose
Secondary outcome [19] 0 0
Cmax -Pharmacokinetic Parameter of Azacitidine
Timepoint [19] 0 0
Cycle 2 Day 1: Pre-dose, 15 min, 0.5, 1, 2 and 4 hr post dose

Eligibility
Key inclusion criteria
* Age >=18 years (For subjects in Taiwan, Age >= 20 years)
* MDS by World Health Organization (WHO) or French-American-British (FAB) classification
* Intermediate 1, intermediate 2 or high risk MDS by IPSS
* At least one platelet count < 75 Gi/L
* Eastern Cooperative Oncology Group (ECOG) Status 0-2
* Adequate baseline organ function defined by the criteria below: total bilirubin =< 1.5x the upper limit of normal (ULN) except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect [haemolytic] bilirubin in the absence of alanine aminotransferase [ALT] abnormality); ALT =< 2.5xULN; creatinine =< 2.5xULN
* Subjects with a corrected QT interval (QTc) <450 milliseconds (msec) or <480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period
* Subject is able to understand and comply with protocol requirements and instructions
* Subject has signed and dated informed consent
* Women must be either of non-child bearing potential, or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study
* Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception during the study and for 3 months following the last dose of study treatment
* Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of randomization until 16 weeks after the last dose of study treatment
* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous treatment with hypomethylating agent or induction chemotherapy for MDS
* Proliferative type chronic myelomonocytic leukemia with white blood cell count >12 Gi/L at any time during the 28 days before Day 1
* History of treatment with eltrombopag, romiplostim or other thrombopoietin receptor (TPO-R) agonists
* Previous allogeneic stem-cell transplantation
* Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator
* Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of investigational product (eltrombopag/placebo)
* Active and uncontrolled infections, including hepatitis B or C
* Human Immunodeficiency Virus (HIV) infection
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or its excipient, or azacitidine, that contraindicates the subjects' participation
* Pregnant or lactating female
* Any serious and/or unstable pre-existing medical condition (including any advanced malignancy other than the disease under study), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures
* French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/04/2016
Sample size
Target
Accrual to date
Final
356
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [2] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [3] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [4] 0 0
Novartis Investigative Site - East Melbourne
Recruitment hospital [5] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Argentina
State/province [10] 0 0
Ciudad Autonoma de Buenos Aires
Country [11] 0 0
Argentina
State/province [11] 0 0
Santa Fe
Country [12] 0 0
Austria
State/province [12] 0 0
Graz
Country [13] 0 0
Austria
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Innsbruck
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Austria
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Linz
Country [15] 0 0
Austria
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Rankweil
Country [16] 0 0
Austria
State/province [16] 0 0
Salzburg
Country [17] 0 0
Austria
State/province [17] 0 0
Steyr
Country [18] 0 0
Austria
State/province [18] 0 0
Vienna
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Belgium
State/province [19] 0 0
Brasschaat
Country [20] 0 0
Belgium
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Brugge
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Belgium
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Leuven
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Belgium
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Lodelinsart
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Belgium
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Turnhout
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Brazil
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Brazil
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Paraná
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Brazil
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Rio Grande Do Sul
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Brazil
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Santa Catarina
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Brazil
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São Paulo
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Brazil
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Rio de Janeiro
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Brazil
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Sao Paulo - SP
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Canada
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Ontario
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Quebec
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Canada
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Québec
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Czechia
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Brno
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Czechia
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Ostrava
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Czechia
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Praha 10
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Czechia
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Praha 2
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Czechia
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Praha
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Aarhus
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Denmark
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Koebenhavn Oe
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Angers Cedex 9
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France
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Caen Cedex 9
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France
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Le Mans
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France
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Paris Cedex 12
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France
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Paris
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France
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Pringy Cedex
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Germany
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Baden-Wuerttemberg
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Germany
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Bayern
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Germany
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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Germany
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Sachsen
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Greece
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Athens,
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Greece
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Larisa
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Greece
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Patra
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Greece
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Thessaloniki
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Hong Kong
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Chai Wan
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Hong Kong
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Hong Kong
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Hong Kong
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Shatin, New Territories
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Hong Kong
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Tuen Mun
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Hungary
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Debrecen
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Hungary
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Szeged
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Ireland
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Dublin
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Ireland
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Galway
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Ireland
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James Street
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Ireland
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Limerick
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Ireland
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Tallaght, Dublin
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Israel
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Haifa
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Israel
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Holon
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Israel
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Jerusalem
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Israel
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Kfar Saba
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Israel
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Petach-Tikva
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Israel
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Tel Aviv
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Italy
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Calabria
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Italy
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Emilia-Romagna
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Italy
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Liguria
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Italy
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Piemonte
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Italy
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Toscana
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Korea, Republic of
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Seoul
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Oaxaca
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Bergen
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Oslo
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Peru
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Lima
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Poland
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Krakow
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Poland
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Legnica
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Poland
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Lublin
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Poland
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Opole
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Poland
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Slupsk
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Torun
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Puerto Rico
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San Juan
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Russian Federation
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Kaluga
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Russian Federation
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Moscow
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Russian Federation
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Penza
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Russian Federation
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St Petersburg
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Russian Federation
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Asturias
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Barcelona
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Gerona
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La Laguna (Santa Cruz De Tenerife)
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Leon
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León
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Madrid
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Majadahonda (Madrid)
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Malaga
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Málaga
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Spain
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Oviedo
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Palma de Mallorca
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Spain
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Pozuelo De Alarcon/Madrid
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Spain
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Pozuelo De Alarcón/Madrid
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Spain
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Salamanca
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Spain
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Valencia
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Sweden
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Goteborg
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Sweden
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Göteborg
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Sweden
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Stockholm
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Sweden
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Uppsala
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Switzerland
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Aarau
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Switzerland
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Bellinzona
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Switzerland
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Bern
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Switzerland
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Zuerich
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Taiwan
State/province [120] 0 0
Changhua
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Taiwan
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Kaohsiung
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Taiwan
State/province [122] 0 0
Taipei
Country [123] 0 0
Thailand
State/province [123] 0 0
Bangkok
Country [124] 0 0
Thailand
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ChiangMai
Country [125] 0 0
Turkey
State/province [125] 0 0
Ankara
Country [126] 0 0
Turkey
State/province [126] 0 0
Izmir
Country [127] 0 0
Turkey
State/province [127] 0 0
Samsun

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02158936