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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03400033


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT03400033
Ethics application status
Date submitted
8/01/2018
Date registered
17/01/2018

Titles & IDs
Public title
Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-Three-times Weekly Dosing in Dialysis (ASCEND-TD)
Scientific title
A Phase 3 Randomized, Double-blind, Active-controlled, Parallel-group, Multi-center Study in Hemodialysis Participants With Anemia of Chronic Kidney Disease to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of Daprodustat Compared to Recombinant Human Erythropoietin, Following a Switch From Recombinant Human Erythropoietin or Its Analogs
Secondary ID [1] 0 0
2017-004372-56
Secondary ID [2] 0 0
204837
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 tablets
Treatment: Drugs - Matching placebo tablets
Treatment: Drugs - Epoetin alfa vials
Treatment: Drugs - Saline vials or bags

Experimental: Daprodustat - Subjects randomized to this arm will receive daprodustat tablets titrated doses from 2 to 48 milligrams orally three-times weekly along with saline by IV route for the 52 weeks treatment period.

Active comparator: Epoetin alfa - Subjects randomized to this arm will receive matching placebo tablets to daprodustat orally three-times weekly and Epoetin alfa by IV route for the 52 weeks treatment period.


Treatment: Drugs: Daprodustat tablets
Round, biconvex, white, film-coated tablet in unit dose strengths 2 and 4 milligrams (7 millimeter tablets), 6, 8 and 10 milligrams (9 millimeter tablets) administered by the oral route.

Treatment: Drugs: Matching placebo tablets
Matching placebo to daprodustat tablets supplied as round, biconvex, white, film-coated tablet in unit dose strengths 2 and 4 milligrams (7 millimeter tablets), 6, 8 and 10 milligrams (9 millimeter tablets) administered by the oral route.

Treatment: Drugs: Epoetin alfa vials
Single-dose, preservative-free vials in unit dose strengths of 2000, 3000, 4000 and 10,000 Units/milliliter administered by the IV route.

Treatment: Drugs: Saline vials or bags
0.9% sodium chloride saline vials or bags administered by the IV route.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in Hemoglobin Levels Over the 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
Mean Average Monthly On-treatment Intravenous (IV) Iron Dose Per Participant
Timepoint [1] 0 0
Day 1 to Week 52
Secondary outcome [2] 0 0
Change From Baseline in Hemoglobin Levels at Week 52
Timepoint [2] 0 0
Baseline (Pre-dose on Day 1) and Week 52
Secondary outcome [3] 0 0
Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52)
Timepoint [3] 0 0
Week 28 to Week 52
Secondary outcome [4] 0 0
Number of Hemoglobin Responders in the Hemoglobin Analysis Range (10 to 11.5 Grams/Deciliter) Over Evaluation Period (Week 28 to Week 52)
Timepoint [4] 0 0
Week 28 to Week 52
Secondary outcome [5] 0 0
Percentage of Participants Permanently Stopping Study Treatment Due to Meeting Rescue Criteria
Timepoint [5] 0 0
Up to Week 52
Secondary outcome [6] 0 0
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at Week 52
Timepoint [6] 0 0
Baseline (Week -4 ) and Week 52
Secondary outcome [7] 0 0
Change From Baseline in SBP, DBP and MAP at End of Treatment
Timepoint [7] 0 0
Baseline (Week -4) and end of treatment (last on-treatment value until Week 52)
Secondary outcome [8] 0 0
Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years
Timepoint [8] 0 0
Up to 52 weeks
Secondary outcome [9] 0 0
Number of Participants With at Least One BP Exacerbation Event During the Study
Timepoint [9] 0 0
Up to 52 weeks
Secondary outcome [10] 0 0
Change From Baseline at Weeks 8, 12, 28 and 52 in Patient Global Impression of Severity (PGI-S)
Timepoint [10] 0 0
Baseline (Pre-dose on Day 1) and Weeks 8, 12, 28, 52
Secondary outcome [11] 0 0
Pre-dose Trough Concentration (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13)
Timepoint [11] 0 0
Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 and Week 52
Secondary outcome [12] 0 0
Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2487818 (M4), GSK2506102 (M5), GSK2506104 (M3), GSK2531398 (M6) and GSK2531401 (M13)
Timepoint [12] 0 0
Pre-dose on Day 1; Pre-dose and at 0.5, 1, 2, 3 hours post-dose on any one post-Baseline visit day between Week 8 and Week 52

Eligibility
Key inclusion criteria
* Subject must be 18 to 99 years of age inclusive, at the time of signing the informed consent.
* Use of any approved rhEPO or analog for at least 8 weeks prior to the screening visit and continuing during the screening period until randomization (Day 1).
* Hgb concentration (measured by HemoCue) within the following range: Week -4: Hgb 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). If Hgb is 11.6 to 11.9 grams/deciliter (7.2 to 7.4 millimoles/liter), up to two retests are allowed; the retest value must be between 8 to 11.5 grams/deciliter (5 to 7.1 millimoles/liter). Day 1: Hgb 8 to 11 grams/deciliter (5 to 6.8 millimoles/liter) and receiving at least the minimum rhEPO or analog dose 3. Hgb>11 to 11.5 grams/deciliter (6.8 to 7.1 millimoles/liter) and receiving greater than the minimum rhEPO or analog dose 3.
* On hemodialysis (including hemofiltration or hemodiafiltration) >90 days prior to screening and continuing during the screening period.
* On hemodialysis (in-center) >=3 times per week.
* Male and female subjects are eligible. A female subject 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 A WOCBP who agrees to follow the contraceptive guidance from at least 28 days prior to first dose of study treatment and for at least 28 days after the last dose of study treatment.
* Capable of giving signed informed consent.
* In France, a subject will be eligible for inclusion in this study if he or she is either affiliated to or beneficiary of a social security category.
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 within 52 weeks after randomization (Day 1).
* Ferritin: <=100 nanograms/milliliter (<=100 micrograms/liter), at screening.
* Transferrin saturation (TSAT): <=20 percent, at screening. If TSAT is 18 to 20 percent, then a retest using a new blood sample can be obtained within 7 days of the final laboratory report; the final retest value must be >20 percent to confirm eligibility.
* Aplasias: History of bone marrow aplasia or pure red cell aplasia.
* Conditions, other than anemia of CKD, which can affect erythropoiesis.
* Myocardial infarction (MI) or acute coronary syndrome within 8 weeks prior to screening through to randomization (Day 1).
* Stroke or transient ischemic attack within 8 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 as determined by the investigator that would contraindicate the use of rhEPO.
* Bazett's correction of QTc interval (QTcB): at Day 1: QTcB >500 milliseconds, or QTcB >530 milliseconds in subjects with bundle branch block. There is no QTc (corrected QT) exclusion for subjects with a predominantly ventricular paced rhythm.
* Liver Disease: presence of any one of the following liver-related laboratory values or conditions, at screening, is exclusionary: ALT >2x upper limit of normal (ULN); Bilirubin >1.5x ULN; or 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.
* Evidence of actively bleeding gastric, duodenal or esophageal ulcer disease OR clinically significant gastro intestinal bleeding <= 8 weeks prior to screening through to randomization (Day 1).
* History of malignancy within 2 years prior to screening through to randomization (Day 1), currently receiving treatment for cancer, or complex kidney cyst (e.g., Bosniak Category IIF, III or IV) >3 centimeters.
* Use of a strong inhibitor of Cytochrome P4502C8 [CYP2C8] (e.g. gemfibrozil) or a strong inducer of CYP2C8 (e.g. rifampin/rifampicin).
* History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product (daprodustat) or epoetin alfa.
* Use of another investigational agent within 30 days or within five half-lives of the investigational agent (whichever is longer) or currently participating in a study of an investigational device prior to screening through to randomization (Day 1).
* Any prior treatment with daprodustat for treatment duration of >30 days.
* 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
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
5/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/06/2020
Sample size
Target
Accrual to date
Final
407
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [2] 0 0
GSK Investigational Site - Parkville
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Mexico
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Santa Fe
Country [17] 0 0
Brazil
State/province [17] 0 0
Bahia
Country [18] 0 0
Brazil
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Paraná
Country [19] 0 0
Brazil
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Rio Grande Do Sul
Country [20] 0 0
Brazil
State/province [20] 0 0
São Paulo
Country [21] 0 0
Brazil
State/province [21] 0 0
Belo Horizonte, Minas Gerais
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Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
France
State/province [23] 0 0
Bayonne
Country [24] 0 0
France
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Epagny Metz-Tessy
Country [25] 0 0
France
State/province [25] 0 0
Le Mans
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France
State/province [26] 0 0
Nice Cedex 1
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France
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Strasbourg
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Italy
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Emilia-Romagna
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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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Anyang-Si, Gyeonggi-do
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Korea, Republic of
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Busan
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Korea, Republic of
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Goyang-si, Gyeonggi-do
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Poland
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Katowice
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Poland
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Lodz
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Poland
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Sandomierz
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Poland
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Tarnowskie Gory
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Poland
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Zyrardow
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Romania
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Constanta
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Romania
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Resita
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Russian Federation
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Kazan
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Russian Federation
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Kolomna
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Russian Federation
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Krasnodar
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Russian Federation
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Krasnogorsk
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Russian Federation
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Mytischi
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Russian Federation
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Novorossiysk
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Russian Federation
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Novosibirsk
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Russian Federation
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Omsk
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Russian Federation
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Orenburg
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Russian Federation
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Penza
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Russian Federation
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Podolsk
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Russian Federation
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Saint-Petersburg
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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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Ufa
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Russian Federation
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Yaroslavl
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Spain
State/province [59] 0 0
Almeria
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Spain
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Badalona
Country [61] 0 0
Spain
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Barcelona
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Spain
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Gerona
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Spain
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Granollers, Barcelona
Country [64] 0 0
Spain
State/province [64] 0 0
Madrid
Country [65] 0 0
Spain
State/province [65] 0 0
Manises (Valencia)
Country [66] 0 0
Spain
State/province [66] 0 0
Sanlúcar De Barrameda (Cádiz)
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Bradford
Country [68] 0 0
United Kingdom
State/province [68] 0 0
London
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Sheffield
Country [70] 0 0
United Kingdom
State/province [70] 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?
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 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 are available at https://clinicaltrials.gov/study/NCT03400033

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
VIC
Funding & Sponsors
Primary sponsor
Commercial sector/Industry
Primary sponsor name
GlaxoSmithKline
Primary sponsor address
Primary sponsor country
Ethics approval
Ethics application status
Approved
 
Public notes
Investigators:
Nigel Toussaint, Royal Melbourne Hospital, Victoria, Parkville, Australia, 3050
Peter Mount, Austin Health, Victoria, Heidelberg, Australia, 3084

Contacts
Principal investigator
Title 65 0
Name 65 0
Address 65 0
Country 65 0
Phone 65 0
Fax 65 0
Email 65 0
Contact person for public queries
Title 66 0
Name 66 0
Address 66 0
Country 66 0
Phone 66 0
Fax 66 0
Email 66 0
[email protected]
Contact person for scientific queries
Title 67 0
Name 67 0
Address 67 0
Country 67 0
Phone 67 0
Fax 67 0
Email 67 0
[email protected]