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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03512197




Registration number
NCT03512197
Ethics application status
Date submitted
26/03/2018
Date registered
30/04/2018

Titles & IDs
Public title
A Global Study of the Efficacy and Safety of Midostaurin + Chemotherapy in Newly Diagnosed Patients With FLT3 Mutation Negative (FLT3-MN) Acute Myeloid Leukemia (AML)
Scientific title
A Phase III, Randomized, Double-blind Study of Chemotherapy With Daunorubicin or Idarubicin and Cytarabine for Induction and Intermediate Dose Cytarabine for Consolidation Plus Midostaurin (PKC412) or Chemotherapy Plus Placebo in Newly Diagnosed Patients With FLT-3 Mutation Negative Acute Myeloid Leukemia (AML)
Secondary ID [1] 0 0
2017-003540-21
Secondary ID [2] 0 0
CPKC412E2301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia (AML) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

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

Experimental: Midostaurin + chemotherapy - Participants received Midostaurin in Induction 50mg twice daily on Day 8 until 48 hrs before start of next cycle. During Induction 2 and consolidation 50mg twice daily on Day 4 until 48 hrs before start of next cycle. During post-consolidation 50mg twice daily for 28 consecutive days of each 28-day treatment cycle up to 12 cycles. For participants who could not tolerate the protocol-specified dosing schedule, dose interruptions and/or reductions were either recommended or mandated allowing participants to continue the study treatment. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation.

Placebo comparator: Placebo + chemotherapy - Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation


Treatment: Drugs: Midostaurin
Midostaurin was provided as 25 mg capsules 8PC, was supplied as double-blind in blister packs and taken orally.

Treatment: Drugs: Placebo
Placebo was provided as 25 mg soft gelatin capsules 8PC, was supplied as double-blind in blister packs and taken orally.

Treatment: Drugs: Chemotherapy
Along with the study drug/placebo, chemotherapy was given as well: either Daunorubicin or Idarubicin and Cytarabine - all taken by i.v.

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

Outcomes
Primary outcome [1] 0 0
Event Free Survival (EFS)
Timepoint [1] 0 0
From date of Randomization up to approx. 30 months
Secondary outcome [1] 0 0
Overall Survival (OS) (Key Secondary)
Timepoint [1] 0 0
Between randomization to date of death up to approx. 30 months
Secondary outcome [2] 0 0
Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Hematological Recovery (CRi) But With Adequate Blood Count Recovery Rate.
Timepoint [2] 0 0
At maximum 93 days from induction therapy start
Secondary outcome [3] 0 0
Percentage of Participants With Minimal Residual Disease (MRD) Negative Status
Timepoint [3] 0 0
from start of treatment up to end of post-consolidation (approximately 17 months)
Secondary outcome [4] 0 0
Percentage of Participants With Minimal Residual Disease (MRD) Negative Status During Post-consolidation Phase
Timepoint [4] 0 0
from start of post-consolidation to end of post-consolidation phase (up to 12 months)
Secondary outcome [5] 0 0
Time to Measurable Residual Disease (MRD) Negativity by Flow Cytometry
Timepoint [5] 0 0
From date of Randomization up to approx. 17 months
Secondary outcome [6] 0 0
Disease-free Survival (DFS)
Timepoint [6] 0 0
From date of CR or CRi with adequate blood count recovery up to approx. 30 months
Secondary outcome [7] 0 0
Cumulative Incidence of Relapse (CIR)
Timepoint [7] 0 0
From date of CR or CRi with adequate blood count recovery up to approx. 30 months
Secondary outcome [8] 0 0
Cumulative Incidence of Death (CID)
Timepoint [8] 0 0
From date of CR or CRi with adequate blood count recovery up to approx. 30 months
Secondary outcome [9] 0 0
Time to CR or CRi With Adequate Blood Count Recovery
Timepoint [9] 0 0
At maximum 93 days from induction therapy start
Secondary outcome [10] 0 0
Time to Partial and Full Neutrophil Recovery
Timepoint [10] 0 0
At maximum 93 days from induction therapy start
Secondary outcome [11] 0 0
Time to Partial and Full Platelet Recovery
Timepoint [11] 0 0
At maximum 93 days from induction therapy start
Secondary outcome [12] 0 0
Plasma Concentrations for Midostaurin and Its Metabolites: CGP52421 and CGP62221 for Non-poor Metabolizers
Timepoint [12] 0 0
from Induction (IND) phase 0hr (predose) to Post-consolidation phase (POSTCONS) 12hr
Secondary outcome [13] 0 0
AUC0-t: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8
Timepoint [13] 0 0
0 - 12 hrs
Secondary outcome [14] 0 0
AUClast: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8
Timepoint [14] 0 0
0 - 12 hrs
Secondary outcome [15] 0 0
Cmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8
Timepoint [15] 0 0
0 - 12 hrs
Secondary outcome [16] 0 0
Tmax: Pharmacokinetic (PK) Parameter for Midostaurin and Its Metabolites: CGP52421 and CGP62221 at Cycle 1, Day 8
Timepoint [16] 0 0
0 - 12 hrs
Secondary outcome [17] 0 0
Total Score for Each Time Point for the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu)
Timepoint [17] 0 0
From date of Randomization up to approx. 18 months
Secondary outcome [18] 0 0
Scores for Each Time Point for the EQ5D-5L (a Visual Analogue Scale (VAS))
Timepoint [18] 0 0
From date of Randomization up to approx. 18 months

Eligibility
Key inclusion criteria
1. Diagnosis of AML (=20% blasts in the bone marrow based on WHO 2016 classification). Patients with APL with PML-RARA are not eligible.
2. Suitability for intensive induction chemotherapy in the judgment of the investigator
3. Documented absence of an ITD and TKD activating mutation at codons D835 and I836 in the FLT3 gene, as determined by analysis in a Novartis designated laboratory using a validated clinical trial assay with clinical cutoff of 0.05 mutant to wild type signal ratio
4. Age =18 years
5. Laboratory values that indicate adequate organ function assessed locally at the screening visit
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Central nervous system (CNS) leukemia
2. Therapy-related secondary AML
3. Isolated extramedullary leukemia
4. Prior therapy for leukemia or myelodysplasia
5. AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment (e.g., azacytidine or decitabine)
6. Prior treatment with a FLT3 inhibitor (e.g., midostaurin, quizartinib, sorafenib)

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 - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Woolloongabba
Recruitment hospital [3] 0 0
Novartis Investigative Site - Prahran
Recruitment hospital [4] 0 0
Novartis Investigative Site - Murdoch
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3181 - Prahran
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Oregon
Country [4] 0 0
Argentina
State/province [4] 0 0
Buenos Aires
Country [5] 0 0
Austria
State/province [5] 0 0
Linz
Country [6] 0 0
Austria
State/province [6] 0 0
Vienna
Country [7] 0 0
Austria
State/province [7] 0 0
Wien
Country [8] 0 0
Belgium
State/province [8] 0 0
Antwerpen
Country [9] 0 0
Belgium
State/province [9] 0 0
Brugge
Country [10] 0 0
Belgium
State/province [10] 0 0
Roeselare
Country [11] 0 0
Brazil
State/province [11] 0 0
RS
Country [12] 0 0
Brazil
State/province [12] 0 0
SP
Country [13] 0 0
Brazil
State/province [13] 0 0
Sao Paulo
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Sofia
Country [15] 0 0
Czechia
State/province [15] 0 0
Brno - Bohunice
Country [16] 0 0
Czechia
State/province [16] 0 0
Plzen-Bory
Country [17] 0 0
France
State/province [17] 0 0
Bayonne Cedex
Country [18] 0 0
France
State/province [18] 0 0
Angers Cedex 1
Country [19] 0 0
France
State/province [19] 0 0
Avignon
Country [20] 0 0
France
State/province [20] 0 0
Dijon
Country [21] 0 0
France
State/province [21] 0 0
Lille Cedex
Country [22] 0 0
France
State/province [22] 0 0
Nantes Cedex 1
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Pierre Benite
Country [25] 0 0
France
State/province [25] 0 0
Toulouse
Country [26] 0 0
Germany
State/province [26] 0 0
Bavaria
Country [27] 0 0
Germany
State/province [27] 0 0
Brandenburg
Country [28] 0 0
Germany
State/province [28] 0 0
Bad Saarow
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Bochum
Country [31] 0 0
Germany
State/province [31] 0 0
Bonn
Country [32] 0 0
Germany
State/province [32] 0 0
Braunschweig
Country [33] 0 0
Germany
State/province [33] 0 0
Darmstadt
Country [34] 0 0
Germany
State/province [34] 0 0
Duesseldorf
Country [35] 0 0
Germany
State/province [35] 0 0
Duisburg
Country [36] 0 0
Germany
State/province [36] 0 0
Eschweiler
Country [37] 0 0
Germany
State/province [37] 0 0
Essen Werden
Country [38] 0 0
Germany
State/province [38] 0 0
Flensburg
Country [39] 0 0
Germany
State/province [39] 0 0
Giessen
Country [40] 0 0
Germany
State/province [40] 0 0
Gottingen
Country [41] 0 0
Germany
State/province [41] 0 0
Hamburg
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Germany
State/province [42] 0 0
Hannover
Country [43] 0 0
Germany
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Homburg
Country [44] 0 0
Germany
State/province [44] 0 0
Karlsruhe
Country [45] 0 0
Germany
State/province [45] 0 0
Kiel
Country [46] 0 0
Germany
State/province [46] 0 0
Leipzig
Country [47] 0 0
Germany
State/province [47] 0 0
Luebeck
Country [48] 0 0
Germany
State/province [48] 0 0
Magdeburg
Country [49] 0 0
Germany
State/province [49] 0 0
Mainz
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Germany
State/province [50] 0 0
Muenchen
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Germany
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Osnabrueck
Country [52] 0 0
Germany
State/province [52] 0 0
Paderborn
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Germany
State/province [53] 0 0
Rostock
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Germany
State/province [54] 0 0
Siegen
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Germany
State/province [55] 0 0
Stuttgart
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Germany
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Ulm
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Germany
State/province [57] 0 0
Wuerzburg
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Germany
State/province [58] 0 0
Zwickau
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Israel
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Haifa
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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
State/province [62] 0 0
AL
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Italy
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AN
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Italy
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BG
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Italy
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BS
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Italy
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CT
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Italy
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MI
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Italy
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MO
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Italy
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PA
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Italy
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PC
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Italy
State/province [71] 0 0
PE
Country [72] 0 0
Italy
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PG
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Italy
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RC
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Italy
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RM
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Italy
State/province [75] 0 0
TA
Country [76] 0 0
Italy
State/province [76] 0 0
TO
Country [77] 0 0
Italy
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VI
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Japan
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Aichi
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Japan
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Ehime
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Japan
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Fukuoka
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Japan
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Fukushima
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Japan
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Gifu
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Hiroshima
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Ibaraki
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Kanagawa
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Nagasaki
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Japan
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Okayama
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Japan
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Osaka
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Japan
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Shizuoka
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Japan
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Tochigi
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Japan
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Tokyo
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Japan
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Aomori
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Japan
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Kyoto
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Japan
State/province [94] 0 0
Yamagata
Country [95] 0 0
Norway
State/province [95] 0 0
Bergen
Country [96] 0 0
Norway
State/province [96] 0 0
Oslo
Country [97] 0 0
Poland
State/province [97] 0 0
Gdansk
Country [98] 0 0
Portugal
State/province [98] 0 0
Lisboa
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Portugal
State/province [99] 0 0
Porto
Country [100] 0 0
Spain
State/province [100] 0 0
Andalucia
Country [101] 0 0
Spain
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Castilla Y Leon
Country [102] 0 0
Spain
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Catalunya
Country [103] 0 0
Spain
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Extremadura
Country [104] 0 0
Spain
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Pais Vasco
Country [105] 0 0
Spain
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Barcelona
Country [106] 0 0
Spain
State/province [106] 0 0
Madrid
Country [107] 0 0
Spain
State/province [107] 0 0
Valencia
Country [108] 0 0
Spain
State/province [108] 0 0
Zaragoza
Country [109] 0 0
Switzerland
State/province [109] 0 0
Bern
Country [110] 0 0
Switzerland
State/province [110] 0 0
Zurich
Country [111] 0 0
Taiwan
State/province [111] 0 0
Chiayi Hsien
Country [112] 0 0
Taiwan
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Taoyuan Taiwan ROC
Country [113] 0 0
Taiwan
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Kaohsiung City
Country [114] 0 0
Taiwan
State/province [114] 0 0
Taipei
Country [115] 0 0
Turkey
State/province [115] 0 0
Adana
Country [116] 0 0
Turkey
State/province [116] 0 0
Ankara
Country [117] 0 0
Turkey
State/province [117] 0 0
Aydin

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?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.