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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00500331




Registration number
NCT00500331
Ethics application status
Date submitted
24/01/2007
Date registered
12/07/2007
Date last updated
6/12/2017

Titles & IDs
Public title
Dose-Ranging Study in Treatment Naive Type 2 Diabetes Mellitus(T2DM)
Scientific title
A Double-blind, Randomized 12-week Study to Evaluate the Safety and Efficacy of GSK189075 Tablets vs Pioglitazone in Treatment Naive Subjects With Type 2 Diabetes Mellitus
Secondary ID [1] 0 0
KG2105255
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK189075
Treatment: Drugs - pioglitazone
Other interventions - Placebo

Experimental: Arm 1 - GSK189075

Placebo comparator: Arm 2 - Placebo

Other: Arm 3 - pioglitazone (active control)


Treatment: Drugs: GSK189075
Experimental Drug

Treatment: Drugs: pioglitazone
Active Control

Other interventions: Placebo
Placebo Comparator

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline (Week 0) in Glycosylated Hemoglobin (HbA1c) (%) at Week 12
Timepoint [1] 0 0
Baseline (Week 0) and Week 12
Secondary outcome [1] 0 0
Change From Baseline in HbA1c (%) at Weeks 4 and 8
Timepoint [1] 0 0
Baseline (Week 0) and Week 4 and Week 8
Secondary outcome [2] 0 0
Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) at Weeks 4, 8 and 12
Timepoint [2] 0 0
Baseline (Week 0) and Week 4, Week 8 and Week 12
Secondary outcome [3] 0 0
Change From Baseline to Week 12 in Fructosamine
Timepoint [3] 0 0
Baseline (Week 0) to Week 12
Secondary outcome [4] 0 0
Change From Baseline to Week 12 in Fasting Insulin
Timepoint [4] 0 0
Baseline (Week 0) to Week 12
Secondary outcome [5] 0 0
Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG =1.7 mmol/L
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C])
Timepoint [6] 0 0
Baseline (Week 0) and Week 4, Week 8 and Week 12
Secondary outcome [7] 0 0
Change From Baseline to Week 12 in Body Weight
Timepoint [7] 0 0
Baseline (Week 0) to Week 12
Secondary outcome [8] 0 0
Change From Baseline to Week 12 in Waist Circumference
Timepoint [8] 0 0
Baseline (Week 0) to Week 12
Secondary outcome [9] 0 0
Change From Baseline in 24-hour Percent of Filtered Glucose Excreted in Urine
Timepoint [9] 0 0
Baseline (Week 0) and Week 12 (24-hour urine collection)
Secondary outcome [10] 0 0
Change From Baseline in Plasma Glucose Area Under the Curve (AUC) During a 2-hour Oral Glucose Tolerance Test (OGTT)
Timepoint [10] 0 0
Baseline (Week 0) and Week 12 (0 to 2 hour OGTT)
Secondary outcome [11] 0 0
Change From Baseline in Insulin AUC During a 2-hour OGTT
Timepoint [11] 0 0
Baseline (Week 0) and Week 12 (0 to 2-hour OGTT)
Secondary outcome [12] 0 0
Change From Baseline in C-peptide AUC During a 2-hr OGTT
Timepoint [12] 0 0
Baseline (Week 0) and Week 12 (0 to 2 hour OGTT)
Secondary outcome [13] 0 0
Number of Participants With On-therapy Adverse Events (AE) and Serious Adverse Events (SAE)
Timepoint [13] 0 0
Up to 12 weeks
Secondary outcome [14] 0 0
Number of Participants With On-therapy Hypoglycemia
Timepoint [14] 0 0
Up to 14 weeks
Secondary outcome [15] 0 0
Number of Participants With Change From Baseline Vital Signs of Potential Clinical Concern
Timepoint [15] 0 0
Up to 14 weeks
Secondary outcome [16] 0 0
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern
Timepoint [16] 0 0
Up to Early withdrawal (Between Week 12 and Week 14)
Secondary outcome [17] 0 0
Number of Participants With Change From Baseline in Standard Laboratory Parameters of Potential Clinical Concern
Timepoint [17] 0 0
Up to 14 weeks

Eligibility
Key inclusion criteria
Inclusion criteria:

* Subjects with a documented diagnosis of T2DM and have an HbA1c level at Visit 1 of =7.0% and =9.5% as measured by a central laboratory. Subjects with HbA1c <7.5% must have a fasting fingerstick glucose =7 mmol/L (126 mg/dL) at Week 0 prior to randomization.
* Subjects who are treatment-naïve and have not taken insulin, or any oral or injectable anti-diabetic medication in the past 3 months and have not taken a glucose lowering agent for =4 weeks at any time in the past, or Subjects who are newly diagnosed and treated with diet and exercise for a minimum of 6 weeks
* Subjects who are 18 to 70 years of age inclusive at the time of Screening.
* Females of non-childbearing and childbearing potential are eligible to participate as follows:

* Women of childbearing potential must be willing to use one of the following contraception methods: intrauterine device, condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent for at least 30 days prior to the start of study medication, throughout the study and the follow-up visit. Note: use of oral contraceptives is not permitted.
* Women of non-child bearing potential are defined as follows: females regardless of age, with functioning ovaries and who have a current documented tubal ligation [Hatcher, 2004] bilateral oophorectomy or total hysterectomy, or females who are post-menopausal).

(Post-menopausal is defined as after one year without menses with an appropriate clinical profile, e.g. age appropriate, >45 years, in the absence of hormone replacement therapy. In addition to the above criteria, if the post-menopausal status is still questionable, a blood sample should be drawn for simultaneous measurement of follicle stimulating hormone and estradiol; values considered to confirm the post-menopausal state are respectively: FSH >40 MIU/mL and estradiol <40pg/mL (<140 pmol/L)).

* Informed Consent: a signed and dated written consent must be obtained from the subject before any procedures are performed.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Metabolic Disease

* Diagnosis of Type 1 diabetes mellitus.
* History of ketoacidosis which has required hospitalization.
* Thyroid disorder [TSH below the lower limit of the reference range (LLRR) of 0.4mIU/L or above the upper limit of the reference range (ULRR) of >5.5 mIU/L at Screening]. Hypothyroidism treated with the same dose and regimen of thyroid hormone replacement for at least 3 months prior to Screening is allowed.
* BMI of <22 or >43 kg/m2.
* Significant weight gain or loss (as defined as >5% of total body weight) in the 3 months prior to Screening.
* Diabetic Medication

* Has taken insulin or any oral or injectable anti-diabetic medication =4 weeks at any time prior to screening.
* Has taken insulin or any oral or injectable anti-diabetic medication within 3 months of screening.
* Cardiovascular Disease

* Recent history or presence of clinically significant acute cardiovascular disease including:

1. Documented myocardial infarction in the 6 months prior to Screening.
2. Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery either planned and/or occurred in the 6 months prior to Screening.
3. Unstable angina in the 6 months prior to Screening.
4. Clinically significant supraventricular arrhythmias requiring medical therapy, or history of nonsustained or sustained ventricular tachycardia. Symptomatic valvular heart disease or valvular heart disease requiring therapy other than endocarditis prophylaxis.
5. Congestive heart failure (CHF, New York Heart Association (NYHA) Class II to IV) requiring pharmacologic treatment. NYHA Class I may be included in accordance with the local prescribing information for pioglitazone.
6. Blood pressure (BP) >150/100mmHg. If a subject is receiving permitted antihypertensive therapy, then they must be on stable dose(s) of therapy for at least 4 weeks prior to Screening.
7. Has a QTc interval (Bazett's) =450msec at Screening on a single ECG or an average value from 3 ECGs taken 5 minutes apart (on local reading of ECG).
8. Other clinically significant ECG abnormalities which, in the opinion of the investigator, may affect the interpretation of efficacy and safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity.
* Fasting triglycerides =400mg/dL (4.56mmol/L) at Screening. If a subject is receiving permitted lipid-lowering therapy, then they must be on a stable dose(s) of therapy for at least 6 weeks prior to Screening. Niacin and bile acid sequestrants are prohibited.
* Hepatic Disease

Has a diagnosis of active hepatitis (hepatitis B surface antigen or hepatitis C antibody), or clinically significant hepatic enzyme elevation including:

Any one of the following enzymes greater than 2 times the upper limit of the reference range (ULRR) value at Screening.

* alanine transaminase (ALT).
* aspartate transaminase (AST).
* alkaline phosphatase (AP). Has a total bilirubin level that is >1.5 times the ULRR at Screening with the exception of suspected or confirmed Gilbert's disease.

* Pancreatic Disease
* Secondary causes of diabetes:
* history of chronic or acute pancreatitis

* Renal Disease
* Significant renal disease at Screening as manifested by:

Glomerular filtration rate (GFR) <60mL/min (as estimated from serum creatinine at Visit 1 and demographic data using the MDRD equation).For the MDRD equation, please refer to the study procedures manual.

Proteinuria of =1+ by urinary dipstick

* Recurrent genitourinary tract infections defined as =2 episodes of complicated or uncomplicated cystitis or pyelonephritis in the 6 months prior to Screening
* A positive qualitative urinary dipstick for leukocytes, red blood cells (RBC) or nitrites at Screening.

* Concurrent Disease
* Has any concurrent condition or any clinically significant abnormality identified on the screening physical examination, laboratory tests (including blood electrolytes), electrocardiogram, including pulmonary, neurological or inflammatory diseases, which, in the opinion of the investigator, may affect the interpretation of efficacy and safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity
* History of significant co-morbid diseases active in the 6 months prior to Screening (e.g., cholecystitis, acute pancreatitis, gastrointestinal disease, chronic diarrhea, etc.)
* Has a history of malignancy within the past five years [other than superficial squamous cell carcinoma which is non-invasive on pathology or basal cell carcinoma which is successfully treated with local excision] and cervical cancer in situ treated definitively at least 6 months prior to Screening

* Concurrent Medication
* Is currently taking or has taken any of the following medications in the 8 weeks prior to Screening:

1. Digoxin
2. Warfarin and other oral anticoagulants (aspirin and non-steroidal anti-inflammatory drugs are permitted)
3. Bile acid sequestrants
4. Niacin (excluding routine vitamin supplementation)
5. Antiobesity agents (including fat absorption blocking agents)
6. Oral or injectable corticosteroids (inhaled and intranasal corticosteroids are permitted)
7. Loop diuretics
8. Monoamine oxidase inhibitors and tricyclic amines
9. Antiretroviral drugs
10. St John's Wort
11. Oral chromium

* Pregnancy & Breast Feeding
* Is currently lactating or pregnant

* Other
* Current smoker who is unable to abstain from smoking while in the clinic at each visit
* Has a history of alcohol or substance abuse within the past year at Screening or alcohol or substance abuse during treatment, as determined by the investigator:
* Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
* Has an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine
* Has participated in any study with an investigational or marketed drug in the 3 months prior to Screening
* In the opinion of the investigator has a risk of non-compliance with study procedures, or cannot read, understand, or complete study related materials, particularly the informed consent
* Known allergy to any of the tablet excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician

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 2
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)
Recruitment outside Australia
Country [1] 0 0
United States of America
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Arizona
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United States of America
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Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Nevada
Country [6] 0 0
United States of America
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New Mexico
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United States of America
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Ohio
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United States of America
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South Carolina
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Texas
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United States of America
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Virginia
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Argentina
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Buenos Aires
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Córdova
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Cordoba
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Mendoza
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Quilmes
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Tucuman
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Bulgaria
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Pleven
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Bulgaria
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Plovdiv
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Bulgaria
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Sofia
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Bulgaria
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Varna
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Chile
State/province [21] 0 0
Región Metro De Santiago
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Costa Rica
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San José
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Czechia
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Brno
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Czechia
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Ceske Budejovice
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Cheb
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Prague
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Semily
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Sumperk
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Usti nad Labem
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Znojmo
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Bayern
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Hessen
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Niedersachsen
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Rheinland-Pfalz
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Berlin
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Gyor
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Nyirtegyhaza
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Pécs
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Szentes
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Szigetvar
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Szombathely
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Veszprem
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Zalaegerszeg
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India
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Bangalore
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India
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Kochi
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Mumbai
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India
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New Delhi
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Pune
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Jelgava
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Limbazi
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Riga
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Talsi
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Tukums
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Lithuania
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Kaunas
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Lithuania
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Vilnius
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Hamilton
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Lima
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Grudziadz
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Lodz
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Porabka
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Wroclaw
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Puerto Rico
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Ponce
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Romania
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Brasov
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Bucharest
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Deva
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Iasi
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Moscow
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Tomsk
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Tumen
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Bellville
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Gauteng
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Parow
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Roodepoort

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.