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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02879305




Registration number
NCT02879305
Ethics application status
Date submitted
22/08/2016
Date registered
25/08/2016
Date last updated
3/12/2021

Titles & IDs
Public title
Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Dialysis (ASCEND-D)
Scientific title
A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared to Recombinant Human Erythropoietin, Following a Switch From Erythropoietin-stimulating Agents
Secondary ID [1] 0 0
2016-000541-31
Secondary ID [2] 0 0
200807
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaemia 0 0
Aspergillosis, Allergic Bronchopulmonary 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Allergies
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 - rhEPO
Treatment: Drugs - Placebo
Treatment: Drugs - Iron therapy

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

Active comparator: rhEPO - Participants on peritoneal dialysis (PD) will be administered darbepoetin alfa subcutaneously (SC) and participants on hemodialysis (HD) will be administered epoetin alfa intravenously (IV).


Treatment: Drugs: Daprodustat
Daprodustat dose is based on prior ESA dose, the dose is adjusted thereafter in order to achieve the target range.

Treatment: Drugs: rhEPO
The initial ESA dose is based on converting the prior ESA dose to the nearest available study rhEPO dose and is administered IV. The dose is adjusted thereafter in order to achieve the target range.

Treatment: Drugs: Placebo
Oral placebo tablets will be taken from Week -4 up to randomization (Day 1).

Treatment: Drugs: Iron therapy
Participants will receive supplemental iron therapy if ferritin is \<=100 ng/mL or TSAT is \<=20%. The investigator will choose the route of administration and dose of iron.

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

Outcomes
Primary outcome [1] 0 0
Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period: Non-inferiority Analysis
Timepoint [1] 0 0
Up to 3.9 person-years for CV follow-up time period
Primary outcome [2] 0 0
Mean Change From Baseline in Hemoglobin (Hgb) Levels During Evaluation Period (Week 28 to Week 52)
Timepoint [2] 0 0
Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)
Secondary outcome [1] 0 0
Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period: Superiority Analysis
Timepoint [1] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [2] 0 0
Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period
Timepoint [2] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [3] 0 0
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period
Timepoint [3] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [4] 0 0
Mean Average Monthly On-treatment IV Iron Dose Per Participant
Timepoint [4] 0 0
Day 1 to Week 52
Secondary outcome [5] 0 0
Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period
Timepoint [5] 0 0
Up to 3.9 person-years for vital status follow-up time period
Secondary outcome [6] 0 0
Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period
Timepoint [6] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [7] 0 0
Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Timepoint [7] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [8] 0 0
Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period
Timepoint [8] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [9] 0 0
Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis)
Timepoint [9] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [10] 0 0
Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period
Timepoint [10] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [11] 0 0
Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period
Timepoint [11] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [12] 0 0
Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period
Timepoint [12] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [13] 0 0
Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period
Timepoint [13] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [14] 0 0
Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period
Timepoint [14] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [15] 0 0
Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period
Timepoint [15] 0 0
Up to 3.9 person-years for CV follow-up time period
Secondary outcome [16] 0 0
Change From Baseline in Post-randomization Hemoglobin Levels at Week 52
Timepoint [16] 0 0
Baseline (Pre-dose on Day 1) and Week 52
Secondary outcome [17] 0 0
Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)
Timepoint [17] 0 0
Week 28 to Week 52
Secondary outcome [18] 0 0
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis
Timepoint [18] 0 0
Week 28 to Week 52
Secondary outcome [19] 0 0
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis
Timepoint [19] 0 0
Week 28 to Week 52
Secondary outcome [20] 0 0
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis
Timepoint [20] 0 0
Week 28 to end of study (3.9 person-years for follow-up time period)
Secondary outcome [21] 0 0
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis
Timepoint [21] 0 0
Week 28 to end of study (3.9 person-years for follow-up time period)
Secondary outcome [22] 0 0
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52
Timepoint [22] 0 0
Baseline (Week -4) and Week 52
Secondary outcome [23] 0 0
Change From Baseline in SBP, DBP, MAP at End of Treatment
Timepoint [23] 0 0
Baseline (Week -4) and 45.1 months
Secondary outcome [24] 0 0
Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years
Timepoint [24] 0 0
Day 1 to end of study (3.9 person-years for follow-up time period)
Secondary outcome [25] 0 0
Number of Participants With at Least One BP Exacerbation Event During Study
Timepoint [25] 0 0
Day 1 to end of study (3.9 person-years for follow-up time period)
Secondary outcome [26] 0 0
Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria
Timepoint [26] 0 0
Day 1 to 45.1 months
Secondary outcome [27] 0 0
Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52
Timepoint [27] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [28] 0 0
Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Timepoint [28] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [29] 0 0
Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52
Timepoint [29] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [30] 0 0
Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Timepoint [30] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [31] 0 0
Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52
Timepoint [31] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52
Secondary outcome [32] 0 0
Change From Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52
Timepoint [32] 0 0
Baseline (Pre-dose on Day 1) and Week 52
Secondary outcome [33] 0 0
Change From Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52
Timepoint [33] 0 0
Baseline (Pre-dose on Day 1) and Week 52
Secondary outcome [34] 0 0
Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52
Timepoint [34] 0 0
Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

Eligibility
Key inclusion criteria
* Age: 18 to 99 years of age (inclusive).
* Erythropoietin-stimulating agents (ESAs): Use of any approved ESA for at least the 6 weeks prior to screening and between screening and randomization.
* Hgb concentration: On Week -8: Hgb 8 to 12 grams per deciliter (g/dL). On randomization (Day 1): Hgb 8 to 11 g/dL and receiving at least the minimum ESA dose. Hgb >11 g/dL to 11.5 g/dL and receiving greater than the minimum ESA dose.
* Dialysis: On dialysis >90 days prior to screening and continuing on the same mode of dialysis from screening (Week -8) through to randomization (Day 1).
* Frequency of Dialysis: Hemodialysis (HD) >=2 times/week and peritoneal dialysis (PD) >=5 times/week. Home hemodialysis >=2 times/week.
* Compliance with placebo [randomization (Day 1) only]: >=80% and <=120% compliance with placebo during run-in period.
* Informed consent (screening only): 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
* Kidney transplant: Planned living-related or living-unrelated kidney transplant within 52 weeks after study start (Day 1).
* Ferritin: <=100 nanograms (ng)/milliliter (mL) (<=100 micrograms/liter [L]) at screening.
* Transferrin saturation (TSAT) (screening only): <=20%.
* Aplasias: History of bone marrow aplasia or pure red cell aplasia.
* 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 <=4 weeks prior to screening through to randomization (Day 1).
* MI or acute coronary syndrome: <=4 weeks prior to screening through to randomization (Day 1).
* Stroke or transient ischemic attack: <=4 weeks prior to screening through to randomization (Day 1).
* Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart Association (NYHA) functional classification system.
* Current uncontrolled hypertension: Current uncontrolled hypertension as determined by the investigator that would contraindicate the use of recombinant human erythropoietin (rhEPO).
* Bazett's corrected QT interval (QTcB) (Day 1): QTcB >500 millisecond (msec), or QTcB >530 msec in subjects with bundle branch block. There is no QT Interval Corrected for Heart Rate (QTc) exclusion for subjects with a predominantly ventricular paced rhythm.
* Alanine transaminase (ALT): >2x upper limit of normal (ULN) at screening.
* Bilirubin: >1.5xULN at screening.
* Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
* Malignancy: 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 (example [e.g.] Bosniak Category II F, III or IV) > 3 centimeter (cm); with the exception of localized squamous cell or basal cell carcinoma of the skin that has been definitively treated >=4 weeks prior to screening.
* Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product, or epoetin alfa or darbepoetin alfa.
* Drugs and supplements: Use of strong inhibitors of Cytochrome P4502C8 (CYP2C8) (e.g., gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin).
* Other study participation: Use of other investigational agent or device prior to screening through to randomization (Day 1).
* Prior treatment with daprodustat: Any prior treatment with daprodustat for treatment duration of >30 days.
* Females only: Subject is pregnant [as confirmed by a positive serum human chorionic gonadotrophin (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 listed in the List of Highly Effective Methods for Avoiding Pregnancy.
* Other Conditions: 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 (e.g., 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
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,SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Concord
Recruitment hospital [2] 0 0
GSK Investigational Site - Kingswood
Recruitment hospital [3] 0 0
GSK Investigational Site - Kogarah
Recruitment hospital [4] 0 0
GSK Investigational Site - Liverpool
Recruitment hospital [5] 0 0
GSK Investigational Site - St Leonards
Recruitment hospital [6] 0 0
GSK Investigational Site - Westmead
Recruitment hospital [7] 0 0
GSK Investigational Site - Wollongong
Recruitment hospital [8] 0 0
GSK Investigational Site - Birtinya
Recruitment hospital [9] 0 0
GSK Investigational Site - Herston
Recruitment hospital [10] 0 0
GSK Investigational Site - Woolloongabba
Recruitment hospital [11] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [12] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [13] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [14] 0 0
GSK Investigational Site - St Albans
Recruitment hospital [15] 0 0
GSK Investigational Site - Nedlands
Recruitment hospital [16] 0 0
GSK Investigational Site - Murdoch
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2750 - Kingswood
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2065 - St Leonards
Recruitment postcode(s) [6] 0 0
2145 - Westmead
Recruitment postcode(s) [7] 0 0
2500 - Wollongong
Recruitment postcode(s) [8] 0 0
4575 - Birtinya
Recruitment postcode(s) [9] 0 0
4006 - Herston
Recruitment postcode(s) [10] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [11] 0 0
5000 - Adelaide
Recruitment postcode(s) [12] 0 0
3168 - Clayton
Recruitment postcode(s) [13] 0 0
3004 - Melbourne
Recruitment postcode(s) [14] 0 0
3021 - St Albans
Recruitment postcode(s) [15] 0 0
6009 - Nedlands
Recruitment postcode(s) [16] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
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Alabama
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United States of America
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Arkansas
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California
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Connecticut
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District of Columbia
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Kentucky
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Louisiana
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Graz
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Hasselt
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Ieper
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Leuven
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Bulgaria
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Blagoevgrad
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Dobrich
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Gabrovo
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Lom
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Lovech
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Montana
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Pazardzhik
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Plovdiv
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Ruse
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Smolyan
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Sofia
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Varna
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Beroun
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Jilemnice
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Pardubice
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Praha 2
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Czechia
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Praha 4
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Czechia
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Sokolov
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Denmark
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Aalborg
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Denmark
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Holstebro
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Denmark
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Kolding
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Denmark
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Odense C
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Denmark
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Svendborg
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Estonia
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Parnu
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Estonia
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Tallinn
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Estonia
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Tartu
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France
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Annonay
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Bois-Guillaume
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Bordeaux
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Boulogne Billancourt
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Caen Cedex 9
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Mulhouse
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Reims
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Tours cedex 9
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Germany
State/province [101] 0 0
Baden-Wuerttemberg
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Salford

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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.