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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02043678




Registration number
NCT02043678
Ethics application status
Date submitted
21/01/2014
Date registered
23/01/2014

Titles & IDs
Public title
Radium-223 Dichloride and Abiraterone Acetate Compared to Placebo and Abiraterone Acetate for Men With Cancer of the Prostate When Medical or Surgical Castration Does Not Work and When the Cancer Has Spread to the Bone, Has Not Been Treated With Chemotherapy and is Causing no or Only Mild Symptoms
Scientific title
A Phase III Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride in Combination With Abiraterone Acetate and Prednisone/Prednisolone in the Treatment of Asymptomatic or Mildly Symptomatic Chemotherapy-naïve Subjects With Bone Predominant Metastatic Castration-resistant Prostate Cancer(CRPC)
Secondary ID [1] 0 0
2013-003438-33
Secondary ID [2] 0 0
15396
Universal Trial Number (UTN)
Trial acronym
ERA 223
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Radium-223 dichloride (Xofigo, BAY88-8223)
Treatment: Drugs - Matching placebo (normal saline)
Treatment: Drugs - Abiraterone
Treatment: Drugs - Prednisone/Prednisolone

Experimental: Radium-223 dichloride + Abi/Pred - Participants received 6 intravenous (IV) administrations of radium-223 dichloride 50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of National Institute of Standards and Technology \[NIST\] update) body weight at intervals of 4 weeks, along with oral abiraterone acetate tablets 1000 milligrams (mg) every day plus prednisone/prednisolone 5 mg twice daily (abi/pred) for 6 cycles, followed by abi/pred until an on-study symptomatic skeletal event (SSE) occurred (or other withdrawal criteria were met)

Placebo comparator: Placebo + Abi/Pred - Participants received 6 IV administrations of placebo matched to radium-223 dichloride at intervals of 4 weeks, along with abi/pred for 6 cycles, followed by abi/pred until an on-study SSE occurred (or other withdrawal criteria were met)


Treatment: Drugs: Radium-223 dichloride (Xofigo, BAY88-8223)
50 kiloBecquerel per kilogram (kBq/kg) (55 kBq/kg after implementation of NIST update) body weight, intravenous injection (IV-slow bolus), every 4 weeks for 6 cycles

Treatment: Drugs: Matching placebo (normal saline)
Intravenous injection ( IV-slow bolus), every 4 weeks for 6 cycles

Treatment: Drugs: Abiraterone
1000 mg once daily, oral, with best supportive care

Treatment: Drugs: Prednisone/Prednisolone
5 mg twice daily, oral, with best supportive care

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

Outcomes
Primary outcome [1] 0 0
Symptomatic Skeletal Event Free Survival (SSE-FS)
Timepoint [1] 0 0
From randomization until first onset of on-study symptomatic skeletal event (SSE) or death, up to 47 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization until death from any cause, up to 67 months
Secondary outcome [2] 0 0
Radiological Progression Free Survival (rPFS)
Timepoint [2] 0 0
From randomization until the date of confirmed radiological progression or death, up to 47 months
Secondary outcome [3] 0 0
Time to Pain Progression
Timepoint [3] 0 0
From randomization until the date of pain progression based on pain score, up to 47 months
Secondary outcome [4] 0 0
Time to Cytotoxic Chemotherapy
Timepoint [4] 0 0
From randomization until the date of first cytotoxic chemotherapy, up to 47 months
Secondary outcome [5] 0 0
Time to Opiate Use for Cancer Pain
Timepoint [5] 0 0
From randomization until the date of opiate use, up to 47 months
Secondary outcome [6] 0 0
Number of Participants With Treatment-emergent Adverse Events
Timepoint [6] 0 0
From start of study treatment until the end of the treatment period, up to 65 months
Secondary outcome [7] 0 0
Number of Subjects With Radium-223/Placebo-related Treatment-emergent Adverse Events Per Maximum Intensity
Timepoint [7] 0 0
From start of study treatment until the end of the treatment period, up to 65 months
Secondary outcome [8] 0 0
Number of Participants With Any Treatment-emergent Additional Primary Malignancies
Timepoint [8] 0 0
From start of study treatment until 4 weeks after last study treatment, up to 65 months
Secondary outcome [9] 0 0
Number of Participants With Treatment-emergent Bone Fractures
Timepoint [9] 0 0
From start of study treatment until 4 weeks after last study treatment, up to 65 months
Secondary outcome [10] 0 0
Number of Participants With Post-treatment Adverse Events
Timepoint [10] 0 0
After the treatment period, up to 46 months
Secondary outcome [11] 0 0
Number of Participants With Any Study Drug-related Post-treatment Adverse Events Per Maximum Intensity
Timepoint [11] 0 0
After the treatment period, up to 46 months
Secondary outcome [12] 0 0
Number of Participants With Post-treatment Chemotherapy-related Blood and Lymphatic System Disorders
Timepoint [12] 0 0
After the treatment period, up to 46 months
Secondary outcome [13] 0 0
Number of Participants With Post-treatment Bone Fractures
Timepoint [13] 0 0
After the treatment period, up to 46 months

Eligibility
Key inclusion criteria
* Histologically confirmed adenocarcinoma of the prostate
* Male subjects of age = 18 years
* Prostate cancer progression documented by prostate specific antigen (PSA) according to the Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
* Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis
* Asymptomatic or mildly symptomatic prostate cancer
* Subjects who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment
* Maintenance of medical castration or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L)
* Eastern Cooperative Oncology Group performance status (ECOG PS) score 0 or 1
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes, mitoxantrone and estramustine
* Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone twice daily
* Pathological finding consistent with small cell carcinoma of the prostate
* History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations
* History of or known brain metastasis
* Malignant lymphadenopathy exceeding 3 cm in short-axis diameter
* Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and during the whole screening period before randomization
* Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Subjects with history of spinal cord compression should have completely recovered
* Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime during the 4- week period prior to randomization.

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,SA,VIC
Recruitment hospital [1] 0 0
- St Leonards
Recruitment hospital [2] 0 0
- Adelaide
Recruitment hospital [3] 0 0
- East Bentleigh
Recruitment hospital [4] 0 0
- Fitzroy
Recruitment hospital [5] 0 0
- Heidelberg
Recruitment hospital [6] 0 0
- Darlinghurst
Recruitment hospital [7] 0 0
- East Melbourne
Recruitment hospital [8] 0 0
- Randwick
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3165 - East Bentleigh
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [7] 0 0
3002 - East Melbourne
Recruitment postcode(s) [8] 0 0
2031 - Randwick
Recruitment outside Australia
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United States of America
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Alaska
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California
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Colorado
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District of Columbia
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Florida
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Georgia
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Indiana
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Louisiana
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Maryland
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Massachusetts
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Michigan
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Missouri
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Nebraska
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Pennsylvania
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Virginia
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Washington
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West Virginia
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Belgium
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Bruxelles - Brussel
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Belgium
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Bruxelles
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Belgium
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Edegem
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Gent
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Brazil
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Brazil
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Rio Grande Do Sul
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Brazil
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Sao Paulo
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Ontario
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Canada
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Quebec
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Finland
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Helsinki
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Kuopio
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Finland
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Seinäjoki
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Finland
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Tampere
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France
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Besancon
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France
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Bordeaux Cedex
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France
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Paris
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France
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POITIERS cedex
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France
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Saint-Herblain
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France
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Toulouse Cedex 9
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Germany
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Baden-Württemberg
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Germany
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Bayern
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Germany
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Hessen
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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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Germany
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Thüringen
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Berlin
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Jerusalem
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Kfar Saba
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Zrifin
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Lazio
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Italy
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Liguria
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Lombardia
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Aichi
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Kumamoto
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Miyazaki
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Japan
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Nagasaki
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Netherlands
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Amsterdam
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Netherlands
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Nijmegen
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Netherlands
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Zwolle
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Norway
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Bodø
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Norway
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Lørenskog
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Norway
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Oslo
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Poland
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Gdansk
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Poland
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Gdynia
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Poland
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Gliwice
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Poland
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Poznan
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Russian Federation
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Moscow
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Russian Federation
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Obninsk
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Singapore
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Singapore
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Spain
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Asturias
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Spain
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Barcelona
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Spain
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Málaga
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Sevilla
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Sweden
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Linköping
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Sweden
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Stockholm
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Sweden
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Sundsvall
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Sweden
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Umea
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Sweden
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Växjö
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United Kingdom
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Lothian
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United Kingdom
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Merseyside
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United Kingdom
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Middlesex
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United Kingdom
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Surrey
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United Kingdom
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Tyne And Wear
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United Kingdom
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West Midlands
Country [118] 0 0
United Kingdom
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Belfast
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United Kingdom
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Leeds
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United Kingdom
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London
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Romford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Janssen Research & Development, LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
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)?
No
No/undecided IPD sharing reason/comment
Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.


What supporting documents are/will be available?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Smith M, Parker C, Saad F, Miller K, Tombal B, Ng ... [More Details]