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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02422615




Registration number
NCT02422615
Ethics application status
Date submitted
1/04/2015
Date registered
21/04/2015

Titles & IDs
Public title
Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer.
Scientific title
A Randomized Double-blind, Placebo-controlled Study of Ribociclib in Combination With Fulvestrant for the Treatment of Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer Who Have Received no or Only One Line of Prior Endocrine Treatment
Secondary ID [1] 0 0
2015-000617-43
Secondary ID [2] 0 0
CLEE011F2301
Universal Trial Number (UTN)
Trial acronym
MONALEESA-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

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

Experimental: Ribociclib + fulvestrant - Ribociclib was administered orally at a daily dose of 600mg for 21 consecutive days within a 28-day cycle. This treatment was combined with fulvestrant, which was administered via intramuscular injections of 500mg every 28 days starting on Day 1 of each cycle. Additionally, an extra dose of fulvestrant was given on Day 15 of Cycle 1. For participants who did not tolerate the protocol-specified dosing schedule, dose adjustments were permitted in order to allow the patient to continue the study treatment.

Placebo comparator: Placebo + fulvestrant - Placebo was administered orally for 21 consecutive days within a 28-day cycle. This treatment was combined with fulvestrant, which was administered via intramuscular injections of 500mg every 28 days starting on Day 1 of each cycle. Additionally, an extra dose of fulvestrant was given on Day 15 of Cycle 1. For participants who did not tolerate the protocol-specified dosing schedule, dose adjustments were permitted in order to allow the patient to continue the study treatment.

Participants were unblinded after the implementation of protocol amendment 4 (29-Jan-20) and were given the option to crossover to treatment with ribociclib and fulvestrant.


Treatment: Drugs: Ribociclib
Ribociclib capsules were administered orally at a daily dose of 600mg for 21 consecutive days within a 28-day cycle.

Treatment: Drugs: Fulvestrant
Fulvestrant was administered via intramuscular injections at a dose of 500mg every 28 days, starting on Day 1 of each cycle. In Cycle 1, an additional dose of Fulvestrant was given on Day 15.

Treatment: Drugs: Placebo
Placebo capsules were administered orally for 21 consecutive days within a 28-day cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) Per Investigator Assessment
Timepoint [1] 0 0
From randomization to first documented progression or death, assessed up to approximately 26 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization to death, assessed up to approximately 46 months
Secondary outcome [2] 0 0
Progression Free Survival (PFS) Per Blinded Independent Review Committee (BIRC)
Timepoint [2] 0 0
From randomization to first documented progression or death, assessed up to approximately 26 months
Secondary outcome [3] 0 0
Overall Response Rate (ORR) Per Investigator Assessment
Timepoint [3] 0 0
Up to approximately 26 months
Secondary outcome [4] 0 0
Clinical Benefit Rate (CBR) Per Investigator Assessment
Timepoint [4] 0 0
Up to approximately 26 months
Secondary outcome [5] 0 0
Time to Response (TTR) Per Investigator Assessment
Timepoint [5] 0 0
From randomization to first response, assessed up to approximately 26 months
Secondary outcome [6] 0 0
Duration of Response (DOR) Per Investigator Assessment
Timepoint [6] 0 0
From first documented response to progression or death, assessed up to approximately 26 months
Secondary outcome [7] 0 0
Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) in One Score Category
Timepoint [7] 0 0
Up to approximately 26 months
Secondary outcome [8] 0 0
Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (GHS/QoL) Scale Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
Timepoint [8] 0 0
Up to approximately 26 months
Secondary outcome [9] 0 0
Change From Baseline in the GHS/QoL Scale Score of the EORTC QLQ-C30
Timepoint [9] 0 0
Baseline, every 8 weeks after randomization during 18 months, then every 12 weeks up to end of treatment; end of treatment; and every 8 or 12 weeks post-treatment until progression (post-treatment efficacy visits), assessed up to approximately 26 months
Secondary outcome [10] 0 0
Ribociclib Plasma Concentrations
Timepoint [10] 0 0
Cycle 1 and Cycle 2 at Day 15 pre-dose and at 2, 4, and 6 hours post-dose. Cycle=28 days
Secondary outcome [11] 0 0
LEQ803 Plasma Concentrations
Timepoint [11] 0 0
Cycle 1 and Cycle 2 at Day 15 pre-dose and at 2, 4, and 6 hours post-dose. Cycle = 28 days

Eligibility
Key inclusion criteria
Key

1. Patients were adults, both male and female, aged = 18 years at the time of providing informed consent. Female patients were required to be postmenopausal. Informed consent was obtained prior to any trial-related activities, following local guidelines.
2. Patients had a confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer, determined through histological and/or cytological examination by a local laboratory. Patients also had HER2-negative breast cancer.
3. Patients had either measurable disease as per RECIST 1.1 criteria or at least one predominantly lytic bone lesion.
4. Patients had advanced breast cancer, which included locoregionally recurrent disease not amenable to curative therapies (such as surgery or radiotherapy) or metastatic breast cancer. Patients fell into one of the following categories:

* Newly diagnosed with advanced/metastatic breast cancer and treatment-naïve.
* Relapsed with documented evidence of relapse more than 12 months after completing (neo)adjuvant endocrine therapy, without any prior treatment for advanced/metastatic disease.
* Relapsed with documented evidence of relapse on or within 12 months from completing (neo)adjuvant endocrine therapy, without any prior treatment for advanced/metastatic disease.
* Relapsed with documented evidence of relapse more than 12 months after completing adjuvant endocrine therapy and subsequently progressed after receiving one line of endocrine therapy (antiestrogen or aromatase inhibitor) for advanced/metastatic disease.
* Newly diagnosed with advanced/metastatic breast cancer at diagnosis and progressed after receiving one line of endocrine therapy (antiestrogen or aromatase inhibitor), with documented evidence of progression.
5. Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Patients had adequate bone marrow and organ function.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with symptomatic visceral disease or disease burden that rendered them ineligible for endocrine therapy, based on the investigator's judgment.

2. Patients who had received prior treatment with chemotherapy (except for neoadjuvant/adjuvant chemotherapy), fulvestrant, or any CDK4/6 inhibitor.

3. Patients with inflammatory breast cancer at the screening stage. 4. Patients with central nervous system (CNS) involvement, unless they were at least 4 weeks from completing prior therapy before initiating the study treatment and had a stable CNS tumor at the time of screening. They were also required not to be receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.

5. Patients with clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.

6. Patients who were currently receiving any of the following substances, which could not be discontinued 7 days prior to initiating treatment:

* Known strong inducers or inhibitors of CYP3A4/5.
* Substances with a known risk of prolonging the QT interval or inducing Torsades de Pointes.
* Substances with a narrow therapeutic window and predominantly metabolized through CYP3A4/5.
* Herbal preparations/medications, dietary supplements.

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 administering the treatment/s
The people assessing the outcomes
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - St Leonards
Recruitment hospital [2] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [3] 0 0
Novartis Investigative Site - East Melbourne
Recruitment hospital [4] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Hawaii
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
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Mississippi
Country [11] 0 0
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New Jersey
Country [12] 0 0
United States of America
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New Mexico
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United States of America
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New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
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United States of America
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Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
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Utah
Country [18] 0 0
United States of America
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Washington
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Austria
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Tyrol
Country [20] 0 0
Austria
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Vienna
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Austria
State/province [21] 0 0
Wien
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Belgium
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Aalst
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Belgium
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Charleroi
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Belgium
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Hasselt
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Belgium
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Leuven
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Belgium
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Liege
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Belgium
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Namur
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Bulgaria
State/province [28] 0 0
Sofia
Country [29] 0 0
Canada
State/province [29] 0 0
British Columbia
Country [30] 0 0
Canada
State/province [30] 0 0
New Brunswick
Country [31] 0 0
Canada
State/province [31] 0 0
Nova Scotia
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
Colombia
State/province [34] 0 0
Bogota
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Colombia
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Monteria
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Czechia
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Czech Republic
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Czechia
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Brno
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Czechia
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Prague 8
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Czechia
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Praha
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Denmark
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Aalborg
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Denmark
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Aarhus
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Denmark
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Copenhagen
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Denmark
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Herlev
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Denmark
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Odense C
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Denmark
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Vejle
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France
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Cedex
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France
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Hauts De Seine
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France
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Marne
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France
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Besancon Cedex
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France
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Bordeaux Cedex
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France
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Bordeaux
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France
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Brest
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France
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Creteil
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France
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Le Mans Cedex
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France
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Lille Cedex
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France
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Limoges
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France
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Paris 13
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France
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Pierre Benite
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France
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Toulon La Seyne Sur Mer
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Germany
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Hessen
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Germany
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Lower Saxony
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Germany
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Augsburg
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Germany
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Berlin
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Germany
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Bielefeld
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Germany
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Bonn
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Dresden
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Germany
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Erlangen
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Germany
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Fuerth
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Heidelberg
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Germany
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Koeln
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Germany
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Luebeck
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Germany
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Muenchen
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Germany
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Mühlhausen
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Germany
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Oldenburg
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Germany
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Ravensburg
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Germany
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Saarbruecken
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Germany
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Troisdorf
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Germany
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Tuebingen
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Germany
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Velbert
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Germany
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Weiden
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Szolnok
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Italy
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AQ
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Italy
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BS
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Italy
State/province [88] 0 0
CT
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Italy
State/province [89] 0 0
LE
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Italy
State/province [90] 0 0
MI
Country [91] 0 0
Italy
State/province [91] 0 0
PI
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Italy
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Napoli
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Jordan
State/province [93] 0 0
Amman
Country [94] 0 0
Korea, Republic of
State/province [94] 0 0
Seoul
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Lebanon
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Ashrafieh
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Lebanon
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Beirut
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Malaysia
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Johor
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Malaysia
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Sarawak
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Mexico
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Oaxaca
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Netherlands
State/province [100] 0 0
Amsterdam
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Netherlands
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Breda
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Netherlands
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Den Haag
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Netherlands
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Deventer
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Netherlands
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Enschede
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Netherlands
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Groningen
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Netherlands
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Hoofddorp
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Netherlands
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Maastricht
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Netherlands
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Nieuwegein
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Netherlands
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Roermond
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Netherlands
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Sittard-Geleen
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Netherlands
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Tilburg
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Norway
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Oslo
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Poland
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Konin
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Poland
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Warszawa
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Portugal
State/province [115] 0 0
Lisboa
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Portugal
State/province [116] 0 0
Porto
Country [117] 0 0
Russian Federation
State/province [117] 0 0
Arkhangelsk
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Russian Federation
State/province [118] 0 0
Tambov
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Singapore
State/province [119] 0 0
Singapore
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Spain
State/province [120] 0 0
Andalucia
Country [121] 0 0
Spain
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Barcelona
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Spain
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Castilla Y Leon
Country [123] 0 0
Spain
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Catalunya
Country [124] 0 0
Spain
State/province [124] 0 0
Galicia
Country [125] 0 0
Spain
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Madrid
Country [126] 0 0
Sweden
State/province [126] 0 0
Eskilstuna
Country [127] 0 0
Sweden
State/province [127] 0 0
Sundsvall
Country [128] 0 0
Sweden
State/province [128] 0 0
Vaxjo
Country [129] 0 0
Switzerland
State/province [129] 0 0
Aarau
Country [130] 0 0
Switzerland
State/province [130] 0 0
Basel
Country [131] 0 0
Switzerland
State/province [131] 0 0
Zuerich
Country [132] 0 0
Thailand
State/province [132] 0 0
Bangkok
Country [133] 0 0
Turkey
State/province [133] 0 0
Istanbul
Country [134] 0 0
Turkey
State/province [134] 0 0
Izmir
Country [135] 0 0
United Kingdom
State/province [135] 0 0
Devon
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Newcastle Upon Tyne

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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.