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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03029208




Registration number
NCT03029208
Ethics application status
Date submitted
20/01/2017
Date registered
24/01/2017

Titles & IDs
Public title
Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-in Incident Dialysis (ASCEND-ID)
Scientific title
A 52-week Open-label (Sponsor-blind), Randomized, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Efficacy and Safety of Daprodustat Compared to Recombinant Human Erythropoietin in Subjects With Anemia Associated With Chronic Kidney Disease Who Are Initiating Dialysis
Secondary ID [1] 0 0
2016-000507-86
Secondary ID [2] 0 0
201410
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaemia 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Blood 0 0 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Daprodustat
Treatment: Drugs - Darbepoetin alfa
Treatment: Drugs - Iron therapy

Experimental: Daprodustat treated anemic subjects - Subjects will receive oral daprodustat once daily.

Active comparator: Darbepoetin alfa treated anemic subjects - Subjects will receive darbepoetin alfa subcutaneously or intravenously.


Treatment: Drugs: Daprodustat
Daprodustat will be supplied as film coated tablets for oral administration containing 1, 2, 4, 6, 8, or 10 mg of daprodustat. Doses of 12, 16, and 24 mg of daprodustat will be provided using multiples of these tablet strengths.

Treatment: Drugs: Darbepoetin alfa
Darbepoetin alfa will be supplied as prefilled syringes (PFS) for SC/IV injection available in strengths: 20, 30, 40, 60, 80, 100 and 150 mcg.

Treatment: Drugs: Iron therapy
Iron therapy will be administered if ferritin is \<=100 ng/mL and/or TSAT is \<=20%.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in Hemoglobin (Hgb) During Evaluation Period (Week 28 to Week 52)
Timepoint [1] 0 0
Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Secondary outcome [1] 0 0
Average Monthly Intravenous Iron Dose (Milligrams) From Baseline to Week 52
Timepoint [1] 0 0
Baseline (Day 1) to Week 52
Secondary outcome [2] 0 0
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Blood Pressure (MAP) at Week 52
Timepoint [2] 0 0
Baseline (Day 1) and Week 52
Secondary outcome [3] 0 0
Change From Baseline in SBP, DBP, MAP at End of Treatment
Timepoint [3] 0 0
Baseline (Day 1) and end of treatment (last on-treatment value until Week 52)
Secondary outcome [4] 0 0
Blood Pressure (BP) Exacerbation Events Rate Per 100 Participant Years
Timepoint [4] 0 0
Up to Week 52
Secondary outcome [5] 0 0
Number of Participants With at Least One Blood Pressure Exacerbation Event During Study
Timepoint [5] 0 0
Up to Week 52
Secondary outcome [6] 0 0
Change From Baseline in Post-randomization Hgb at Week 52
Timepoint [6] 0 0
Baseline (Day 1) and Week 52
Secondary outcome [7] 0 0
Number of Hgb Responders (Hgb in the Analysis Range of 10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)
Timepoint [7] 0 0
Weeks 28 to 52
Secondary outcome [8] 0 0
Percentage of Time for Which Hgb Was Within the Analysis Range (10 to 11.5 g/dL) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis
Timepoint [8] 0 0
Weeks 28 to 52
Secondary outcome [9] 0 0
Percentage of Time for Which Hgb Was Within the Analysis Range (10 to 11.5 g/dL) During Evaluation Period (Week 28 to Week 52): Superiority Analysis
Timepoint [9] 0 0
Weeks 28 to 52
Secondary outcome [10] 0 0
Number of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria
Timepoint [10] 0 0
Up to Week 52
Secondary outcome [11] 0 0
Change From Baseline in Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52
Timepoint [11] 0 0
Baseline (Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [12] 0 0
Change From Baseline in Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Timepoint [12] 0 0
Baseline (Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [13] 0 0
Change From Baseline in SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52
Timepoint [13] 0 0
Baseline (Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [14] 0 0
Change From Baseline in Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 28, 52
Timepoint [14] 0 0
Baseline (Day 1), Weeks 28 and 52
Secondary outcome [15] 0 0
Change From Baseline in Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 28, 52
Timepoint [15] 0 0
Baseline (Day 1), Weeks 28 and 52
Secondary outcome [16] 0 0
Change From Baseline in Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52
Timepoint [16] 0 0
Baseline (Day 1) and Week 52
Secondary outcome [17] 0 0
Change From Baseline in EQ Visual Analogue Scale (EQ-VAS) at Week 52
Timepoint [17] 0 0
Baseline (Day 1) and Week 52
Secondary outcome [18] 0 0
Change From Baseline in Chronic Kidney Disease- Anemia Symptoms Questionnaire (CKD-AQ) at Week 52
Timepoint [18] 0 0
Baseline (Day 1) and Week 52
Secondary outcome [19] 0 0
Change From Baseline in Patient Global Impression of Severity (PGI-S)
Timepoint [19] 0 0
Baseline (Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [20] 0 0
Plasma Concentration of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)
Timepoint [20] 0 0
Pre-dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12
Secondary outcome [21] 0 0
Observed Concentration at Dosing Interval (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)
Timepoint [21] 0 0
Pre-Dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12
Secondary outcome [22] 0 0
Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)
Timepoint [22] 0 0
Pre-Dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12

Eligibility
Key inclusion criteria
* 18 to 99 years of age inclusive.
* Planning to start chronic dialysis within the next 6 weeks (from the date of the screening visit) OR have started and received dialysis (as specified below) for end-stage renal disease for a maximum of <=90 days immediately prior to randomization and is not expected to stop dialysis during the duration of the trial: HD >=2 times per week or PD >=4 times per week including incremental schedule; subjects on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) are eligible.
* Hemoglobin concentration as measured by HemoCue (range inclusive): 8 to 10.5 g/dL (5-6.5 millimoles per liter [mmol/L]) at screening and 8-11.0 g/dL (5 to 6.8 mmol/L) at randomization.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Planned living-related or living-unrelated kidney transplant during the study.
* Ferritin: <=100 nanograms per milliliter (ng/mL) (<=100 micrograms per liter [mcg/L]) at screening or after IV iron supplementation.
* Transferrin saturation (TSAT): <=20% at screening or after IV iron supplementation.
* Vitamin B12 (cobalamin): Below the lower limit of the reference range at screening or after vitamin B12 supplementation.
* Folate: <2.0 ng/mL (<4.5 nanomoles per liter [nmol/L]) at screening.
* Aplasias: History of bone marrow aplasia or pure red cell aplasia (PRCA).
* Other causes of anemia: Untreated pernicious anemia, thalassemia major, sickle cell disease, or myelodysplastic syndrome.
* Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant GI bleeding <=10 weeks prior to screening through to randomization (Day 1).
* Use of any Erythropoiesis-stimulating agent (ESA) treatment within 8 weeks prior to screening except for limited use as part of dialysis initiation. Note : Limited use is defined as no more than 6 weeks of short acting ESA (rhEPO or biosimilars; maximum of 20000 unit total) or long acting ESA (darbepoetin alfa [maximum of 100 mcg total] or methoxy polyethylene glycol-epoetin beta [maximum of 125 mcg total]) received before or after starting dialysis.
* Myocardial infarction or acute coronary syndrome: <=10 weeks prior to screening through to randomization (Day 1).
* Stroke or transient ischemic attack: <=10 weeks prior to screening through to randomization (Day 1).
* Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
* Current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of rhEPO.
* QT correction using Bazett's (QTcB) (Day 1): QTcB >500 milliseconds (msec), or QTcB >530 msec in subjects with bundle branch block. There is no QTc exclusion for subjects with a predominantly ventricular paced rhythm.
* Liver disease (any one of the following): 1. Alanine transaminase (ALT) >2 times upper limit of normal (ULN) (screening only). 2. Bilirubin >1.5 times ULN (screening only) (NOTE: Isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 3. Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including asymptomatic gallstones, chronic hepatitis B or C, or Gilbert's syndrome) are acceptable if subject otherwise meets entry criteria.
* History of malignancy within the 2 years prior to screening through to randomization (Day 1), or currently receiving treatment for cancer, or complex kidney cyst (i.e. Bosniak Category II F, III or IV) >3 centimeter (cm). The only exception is localized squamous cell or basal cell carcinoma of the skin that has been definitively treated >=10 weeks prior to screening.
* History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product or to darbepoetin alfa.
* Use of strong Cytochrome P4502C8 (CYP2C8) inhibitors (example gemfibrozil) or strong CYP2C8 inducers (example rifampin/rifampicin).
* Use of other investigational agent or device prior to screening through to randomization (Day 1). At screening, this exclusion applies to use of the investigational agent within 30 days or within five half-lives (whichever is longer).
* Any prior treatment with daprodustat for treatment duration of >30 days.
* Females only: Subject is pregnant [as confirmed by a positive serum human chorionic gonadotropin (hCG) test for females of reproductive potential (FRP) only], subject is breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options in the List of Highly Effective Methods for Avoiding Pregnancy.
* Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (example intolerance to rhEPO) or prevent understanding of the aims or investigational procedures or possible consequences of the study.

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
Open (masking not used)
Who is / are masked / blinded?



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
11/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/09/2020
Sample size
Target
Accrual to date
Final
312
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [2] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [3] 0 0
GSK Investigational Site - St Albans
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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Connecticut
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Iowa
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United States of America
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Louisiana
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United States of America
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Maryland
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United States of America
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Mississippi
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Missouri
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New York
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Texas
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Virginia
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Argentina
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Buenos Aires
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Argentina
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Formosa
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Argentina
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Mendoza
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Argentina
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San Miguel de Tucumán
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Canada
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Ontario
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Canada
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Quebec
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Germany
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Nordrhein-Westfalen
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Germany
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Rheinland-Pfalz
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Germany
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Wiesbaden
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India
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Bangalore
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India
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Chennai
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India
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Delhi
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Gurgaon
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Kozhikode
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New Delhi
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Pune
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Secunderabad
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India
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Thiruvananthapuram
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Italy
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Liguria
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Italy
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Lombardia
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Sardegna
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Korea, Republic of
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Anyang-Si, Gyeonggi-do
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Korea, Republic of
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Bucheon-si,
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Ipoh
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Jalisco
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Mexico
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Yucatán
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Mexico
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Aguascalientes
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Mexico
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Tlalnepantla
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Poland
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Gdansk
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Kolo
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Krakow
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Lodz
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Ostroda
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Ostroleka
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Poland
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Szczecin
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Russian Federation
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Irkutsk
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Russian Federation
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Mytishchi
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Russian Federation
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Omsk
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Russian Federation
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Smolensk
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Russian Federation
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St-Petersburg
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Russian Federation
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St. Petersburg
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Russian Federation
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Volzhskiy
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South Africa
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Cape Town.
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Puerto Real
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Spain
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Sevilla
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United Kingdom
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Birmingham
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United Kingdom
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Doncaster
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United Kingdom
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London
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United Kingdom
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Middlesbrough

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

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
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?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Available to whom?
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicalstudydatarequest.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03029208