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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03409107




Registration number
NCT03409107
Ethics application status
Date submitted
8/01/2018
Date registered
24/01/2018

Titles & IDs
Public title
Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat in Non-Dialysis Subjects Evaluating Hemoglobin (Hgb) and Quality of Life (ASCEND-NHQ)
Scientific title
A 28-week, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-center, Study in Recombinant Human Erythropoietin (rhEPO) naïve Non-dialysis Participants With Anemia Associated With Chronic Kidney Disease to Evaluate the Efficacy, Safety and Effects on Quality of Life of Daprodustat Compared to Placebo
Secondary ID [1] 0 0
2017-002270-39
Secondary ID [2] 0 0
205270
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 (GSK1278863)
Treatment: Drugs - Placebo
Treatment: Drugs - Iron therapy

Experimental: Daprodustat receivers - Participants will receive oral daprodustat once daily

Placebo comparator: Placebo receivers - Participants will receive oral placebo once daily


Treatment: Drugs: Daprodustat (GSK1278863)
Daprodustat will be available as 9 millimeter (mm) or 7 mm film-coated tablets. Daprodustat will be administered once daily via oral route and can be taken without regard to food.

Treatment: Drugs: Placebo
Daprodustat matching placebo will be available as 9 mm or 7 mm film coated tablets. Placebo will be administered once daily via oral route and can be taken without regard to food.

Treatment: Drugs: Iron therapy
Iron therapy will be administered if ferritin is \<50 Nano gram per milliliter and/or TSAT is \<15 percent.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28)
Timepoint [1] 0 0
Baseline (Day 1) and Week 24 to Week 28
Secondary outcome [1] 0 0
Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period
Timepoint [1] 0 0
Baseline (Day 1) and Week 24 to Week 28
Secondary outcome [2] 0 0
Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28
Timepoint [2] 0 0
Baseline (Day 1) and Week 28
Secondary outcome [3] 0 0
Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive)
Timepoint [3] 0 0
Week 24 to Week 28
Secondary outcome [4] 0 0
Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Hodges-Lehmann Estimate)
Timepoint [4] 0 0
Week 24 to Week 28
Secondary outcome [5] 0 0
Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Mann-Whitney Estimate)
Timepoint [5] 0 0
Week 24 to Week 28
Secondary outcome [6] 0 0
Change From Baseline in Post-randomization Hgb at Week 28
Timepoint [6] 0 0
Baseline (Day 1) and Week 28
Secondary outcome [7] 0 0
Rate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria
Timepoint [7] 0 0
Up to Week 28
Secondary outcome [8] 0 0
Change From Baseline by Domain and Single Item Scores on the Chronic Kidney Disease -Anemia Questionnaire (CKD-AQ) Symptom Questionnaire
Timepoint [8] 0 0
Baseline (Day 1) and Week 28
Secondary outcome [9] 0 0
Change From Baseline in Patient Global Impression of Severity (PGI-S)
Timepoint [9] 0 0
Baseline (Day 1) and Week 28
Secondary outcome [10] 0 0
Change From Baseline in the SF-36 Physical Functioning Domain
Timepoint [10] 0 0
Baseline (Day 1) and Week 28
Secondary outcome [11] 0 0
Change From Baseline of the SF-36 Individual Items in the Vitality Domain
Timepoint [11] 0 0
Baseline (Day 1) and Week 28
Secondary outcome [12] 0 0
Number of Participants Currently Employed as Per Work Productivity and Activity Impairment Questionnaire: Anemic Symptoms Clinical Practice Version (WPAI-ANS-CPV)
Timepoint [12] 0 0
Week 8, Week 12 and Week 28
Secondary outcome [13] 0 0
Change From Baseline in WPAI-ANS-CPV: Percent Time Missed From Work
Timepoint [13] 0 0
Baseline (Day 1), Week 8, Week 12 and Week 28
Secondary outcome [14] 0 0
Change From Baseline in WPAI-ANS-CPV: Mean Hours Missed From Work in the Past 7 Days
Timepoint [14] 0 0
Baseline (Day 1), Week 8, Week 12 and Week 28
Secondary outcome [15] 0 0
Change From Baseline in WPAI: Percent Impairment at Work
Timepoint [15] 0 0
Baseline (Day 1), Week 8, Week 12 and Week 28
Secondary outcome [16] 0 0
Change From Baseline in WPAI: Percent Overall Work Impairment
Timepoint [16] 0 0
Baseline (Day 1), Week 8, Week 12 and Week 28
Secondary outcome [17] 0 0
Change From Baseline in WPAI: Percent Regular Daily Activity Impairment
Timepoint [17] 0 0
Baseline (Day 1), Week 8, Week 12 and Week 28
Secondary outcome [18] 0 0
Change From Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) Utility Score
Timepoint [18] 0 0
Baseline (Day 1) and Week 28
Secondary outcome [19] 0 0
Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score
Timepoint [19] 0 0
Baseline (Day 1) and Week 28
Secondary outcome [20] 0 0
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) at Week 28
Timepoint [20] 0 0
Baseline (Day 1) and Week 28
Secondary outcome [21] 0 0
Percentage of Participants With at Least One Blood Pressure (BP) Exacerbation Event
Timepoint [21] 0 0
Up to Week 28

Eligibility
Key inclusion criteria
* >=18 years of age at the time of signing the informed consent.
* Have CKD, confirmed at screening: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by Estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
* Participants with Stable HemoCue Hgb from 8.5 to 10.5 at screening visit (Week -4) and from 8.5 to 10.0 g/dL at randomization (Day 1).
* Participants may receive up to one intravenous (IV) iron dose within the 8 weeks prior to screening and NO IV iron use between screening visit and randomization (Day 1).
* If needed, participant may be on stable maintenance oral iron supplementation. There should be <50% change in overall dose and no change in type of iron prescribed in the 4 weeks prior to Day 1 randomization visit.
* Male and female participants are eligible. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 weeks after the last dose of study treatment.
* Capable of giving signed informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participants who are on dialysis or clinical evidence of impending need to initiate dialysis within 180 days after randomization (Day 1).
* Planned living-related or living-unrelated kidney transplant within 28 weeks after randomization (Day 1).
* Transferrin saturation (TSAT) <15 percent (Screening only).
* Ferritin <50 nanograms per milliliter (ng/mL) (Screening only).
* History of rhEPO or rhEPO analogue use within the 8 weeks prior to screening and rhEPO use between screening and randomization (Day 1).
* History of transfusion within the 8 weeks prior to screening and transfusion between screening and randomization (Day 1).
* History of bone marrow aplasia or pure red cell aplasia (PRCA).
* Participants with Megaloblastic anemia (untreated pernicious anemia and folate deficiency), thalassemia major, sickle cell disease or myelodysplastic syndrome.
* Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal (GI) bleeding <= 8 weeks prior to screening through to randomization (Day 1).
* History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
* Use of strong inhibitor of CYP2C8 (for example, gemfibrozil) or strong inducers of CYP2C8 (for example, rifampin/rifampicin).
* Ferric citrate use within 4 weeks prior to randomization (Day 1).
* Use of other investigational agent or device prior to screening through to randomization (Day 1).
* Any prior treatment with daprodustat for a treatment duration of >30 days.
* MI or acute coronary syndrome within the 8 weeks prior to screening through to randomization. (Day 1).
* Stroke or transient ischemic attack within the 8 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.
* QT interval corrected by Bazett's formula (QTcB) >500 milliseconds (msec) or QTcB >530 msec in participants with bundle branch block. There is no corrected QT interval (QTc) exclusion for participants with a predominantly paced rhythm.
* Alanine transaminase (ALT) >2x upper limit of normal (ULN) at screening (Week -4).
* Bilirubin >1.5xULN at screening (Week -4).
* 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.
* 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 (for example, Bosniak Category II F, III or IV) > 3 centimeters (cm).
* Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
* Current uncontrolled hypertension as determined by the investigator.

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/10/2020
Sample size
Target
Accrual to date
Final
614
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [2] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [3] 0 0
GSK Investigational Site - Parkville
Recruitment hospital [4] 0 0
GSK Investigational Site - Murdoch
Recruitment hospital [5] 0 0
GSK Investigational Site - Fitzroy
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
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
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Mississippi
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Hampshire
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Virginia
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Argentina
State/province [21] 0 0
Buenos Aires
Country [22] 0 0
Argentina
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Córdova
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Argentina
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Santa Fe
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Brazil
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Bahia
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Brazil
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Espírito Santo
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Brazil
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São Paulo
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Canada
State/province [27] 0 0
British Columbia
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Canada
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Ontario
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Canada
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Quebec
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France
State/province [30] 0 0
Grenoble cedex 9
Country [31] 0 0
France
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Le Mans cedex 9
Country [32] 0 0
France
State/province [32] 0 0
Marseille cedex 5
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France
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Melun
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France
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Mulhouse cedex
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France
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Nantes Cedex 1
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France
State/province [36] 0 0
Nice Cedex 1
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France
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Saint-Priest en Jarez
Country [38] 0 0
Italy
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Calabria
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Italy
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Campania
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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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Lombardia
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Italy
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Veneto
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Korea, Republic of
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Busan
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Korea, Republic of
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Daegu-si
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Korea, Republic of
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Daegu
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Seongnam-si, Gyeonggi-do
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Korea, Republic of
State/province [49] 0 0
Seoul
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Mexico
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Guanajuato
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Mexico
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Jalisco
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Mexico
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Nuevo León
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Veracruz
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Yucatán
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Mexico
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Guadalajara
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Mexico
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Merida
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Poland
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Bialystok
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Ciechanow
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Krakow
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Lodz
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Lublin
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Olawa
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Pleszew
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Sosnowiec
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Swidnik
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Szczecin
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Tczew
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Warszawa
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Romania
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Brasov
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Romania
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Bucharest
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Romania
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Cluj-Napoca
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Romania
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Craiova
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Romania
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Deva
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Romania
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Oradea
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Romania
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Targu Mures
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Romania
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Timisoara
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Izhevsk
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Russian Federation
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Kaliningrad
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Russian Federation
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Kemerovo
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Russian Federation
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Krasnoyarsk
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Russian Federation
State/province [81] 0 0
Moscow
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Russian Federation
State/province [82] 0 0
Nizhniy Novgorod
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Pyatigorsk
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Rostov-on-Don
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Ryazan
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Saint Petersburg
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Stavropol
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Russian Federation
State/province [88] 0 0
Yaroslavl
Country [89] 0 0
Spain
State/province [89] 0 0
Badalona
Country [90] 0 0
Spain
State/province [90] 0 0
Madrid
Country [91] 0 0
Spain
State/province [91] 0 0
Santiago de Compostela
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Kent
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Derby
Country [94] 0 0
United Kingdom
State/province [94] 0 0
London
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Peterborough
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Plymouth
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Shrewsbury
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Swansea

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?
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

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)?
Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Available to whom?
Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.gsk.com/en-gb/innovation/trials/data-transparency


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03409107