The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00495469




Registration number
NCT00495469
Ethics application status
Date submitted
29/06/2007
Date registered
3/07/2007
Date last updated
30/10/2017

Titles & IDs
Public title
Dose-Ranging Study In Subjects With Type 2 Diabetes Mellitus Who Are Treatment-Naive
Scientific title
A Once-Daily Dose-Ranging Study of GSK189075 Versus Placebo In The Treatment of Type 2 Diabetes Mellitus in Treatment-Naïve Subjects
Secondary ID [1] 0 0
KG2110375
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 - Placebo

Experimental: GSK189075 - Participants will receive GSK189075 for 12 weeks

Placebo comparator: Placebo - Participants will receive GSK189075 matching Placebo for 12 weeks


Treatment: Drugs: GSK189075
GSK189075 is available as a white, capsule-shaped tablet dosage form containing 50mg, 125mg, 250mg or 500mg of GSK189075 per tablet

Treatment: Drugs: Placebo
Available as Placebo matching tablet to GSK189075

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

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in Hemoglobin A1c (Glycosylated Hemoglobin) (HbA1c) at Week 12
Timepoint [1] 0 0
Baseline (Week 0) and at Week 12
Secondary outcome [1] 0 0
Mean Change From Baseline in HbA1c at Weeks 4 and 8
Timepoint [1] 0 0
Baseline (Week 0) and at Week 4 nad 8
Secondary outcome [2] 0 0
Mean Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG)
Timepoint [2] 0 0
Baseline (Week 0) and at Week 12
Secondary outcome [3] 0 0
Mean Change From Baseline to Week 12 in Fructosamine (Corrected)
Timepoint [3] 0 0
Baseline (Week 0) and at Week 12
Secondary outcome [4] 0 0
Number of Participants Who Were HbA1c Responders at Week 12
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Number of Participants Who Were Fasting Plasma Glucose (FPG) Responders at Week 12
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
Mean Change From Baseline to Week 12 in Triglycerides
Timepoint [6] 0 0
Baseline (Week 0) and at Week 12
Secondary outcome [7] 0 0
Mean Change From Baseline to Week 12 in Total Cholesterol
Timepoint [7] 0 0
Baseline (Week 0) and at Week 12
Secondary outcome [8] 0 0
Mean Change From Baseline to Week 12 in Low Density Lipoprotein Cholesterol (LDL-c)
Timepoint [8] 0 0
Baseline (Week 0) and Week 12
Secondary outcome [9] 0 0
Mean Change From Baseline to Week 12 in High Density Lipoprotein Cholesterol (HDL-c)
Timepoint [9] 0 0
Baseline (Week 0) and Week 12
Secondary outcome [10] 0 0
Mean Change From Baseline to Week 12 in LDL-c/HDL-c Ratio
Timepoint [10] 0 0
Baseline (Week 0) and Week 12
Secondary outcome [11] 0 0
Mean Change From Baseline to Week 12 in Total Cholesterol/HDL-c Ratio
Timepoint [11] 0 0
Baseline (Week 0) and Week 12
Secondary outcome [12] 0 0
Mean Change From Baseline to Week 12 in Body Weight
Timepoint [12] 0 0
Baseline (Week 0) and Week 12
Secondary outcome [13] 0 0
Number of Participants With Any On-therapy Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [13] 0 0
Up to Week 12
Secondary outcome [14] 0 0
Number of Participants With On-therapy Hypoglycemia
Timepoint [14] 0 0
Up to Week 12
Secondary outcome [15] 0 0
Number of Participants With Vital Signs of Potential Clinical Importance (PCI) at Any Time on Therapy
Timepoint [15] 0 0
Up to Week 12
Secondary outcome [16] 0 0
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Any Time Post-Baseline
Timepoint [16] 0 0
Up to Week 12
Secondary outcome [17] 0 0
Number of Participants With Abnormal Chemistry Value of PCI at Any Time on Therapy
Timepoint [17] 0 0
Up to Week 12
Secondary outcome [18] 0 0
Number of Participants With Abnormal Hematology Value of PCI at Any Time on Therapy
Timepoint [18] 0 0
Up to Week 12

Eligibility
Key inclusion criteria
* Subjects with a documented diagnosis of T2DM and HbA1c =7.0% and =9.5% measured by the central laboratory at Visit 1.

* Note: Subjects with HbA1c <7.5% must have a fasting fingerstick glucose =7 mmol/L (126 mg/dL) at Week 0, prior to randomization.
* Note: The proportion of subjects who are randomized with an HbA1c <7.5% will be limited to be no more than 20% (approximately 51 subjects)
* 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 childbearing and non-childbearing and 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 who have a current documented tubal ligation, or who are surgically sterile (i.e. documented total hysterectomy or bilateral oophorectomy), or females who are post-menopausal.

All females must have a negative urine pregnancy test on the day of, and prior to randomization.

* 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 <0.4 MIU/L (<0.4 MCIU/mL) or >5.5 mIU/L (>5.5 MCIU/mL) at Screening
* BMI of <22 kg/m2 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 within 3 months of screening
* Has taken insulin or any oral or injectable anti-diabetic medication =4 weeks at any time in the past
* Cardiovascular Disease

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

* Documented myocardial infarction in the 6 months prior to Screening.
* 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.
* Unstable angina in the 6 months prior to Screening.
* 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.
* Congestive heart failure (CHF, New York Heart Association (NYHA) Class II to IV) requiring pharmacologic treatment or the NYHA Class criteria in accordance with the local prescribing information for pioglitazone.
* 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.
* Based on local readings, the subject has an initial QTc interval (Bazett's)=450msec at Screening, and after two additional ECGs taken 5 minutes apart, the average of the QTC interval from the three ECGs is =450msec.
* Other clinically significant ECG abnormalities which, in the opinion of the Investigator, may affect the interpretation of efficacy or 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 aminotransferase (ALT)
* aspartate aminotransferase (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 calculated by Quest at Visit using the Modification of Diet in Renal Disease (MDRD) equation

•=1+ protein on urine dipstick
* Trace or =1+ leukocyte esterase on urine dipstick
* Trace or =1+ blood on urine dipstick
* Positive nitrite on urine dipstick
* Recurrent genitourinary tract infections defined as =2 episodes of complicated or uncomplicated cystitis or pyelonephritis in the 6 months prior to Screening.

* Concurrent Disease
* Has any concurrent condition or any clinically significant abnormality identified on the screening physical examination, laboratory tests (including blood electrolytes), ECG, 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.).
* History of malignancy within the past 5 years other than superficial squamous cell carcinoma (non-invasive on pathology) or basal cell carcinoma (successfully treated with local excision).
* History of 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:

* Digoxin
* Warfarin and other oral anticoagulants (aspirin and non-steroidal anti-inflammatory drugs are permitted)
* Bile acid sequestrants
* Niacin (excluding routine vitamin supplementation)
* Antiobesity agents (including fat absorption blocking agents)
* Oral or injectable corticosteroids (inhaled, topical and intranasal corticosteroids are permitted)
* Loop diuretics
* Monoamine oxidase inhibitors and tricyclic amines
* Antiretroviral drugs
* St John's Wort
* Oral chromium 9.Breast Feeding 10.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 alcohol of >21 units or an average daily intake of >3 units (males) or an average weekly intake of >14 units or an average daily intake of >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 or capsule excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician, contraindicates participation.

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
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
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Mississippi
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Nevada
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New Mexico
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
Canada
State/province [24] 0 0
British Columbia
Country [25] 0 0
Canada
State/province [25] 0 0
New Brunswick
Country [26] 0 0
Canada
State/province [26] 0 0
Newfoundland and Labrador
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
Canada
State/province [29] 0 0
Québec
Country [30] 0 0
Czechia
State/province [30] 0 0
Brno
Country [31] 0 0
Czechia
State/province [31] 0 0
Praha 10
Country [32] 0 0
Czechia
State/province [32] 0 0
Praha 5
Country [33] 0 0
Estonia
State/province [33] 0 0
Parnu
Country [34] 0 0
Estonia
State/province [34] 0 0
Tallinn
Country [35] 0 0
Estonia
State/province [35] 0 0
Tallin
Country [36] 0 0
Estonia
State/province [36] 0 0
Tartu
Country [37] 0 0
Germany
State/province [37] 0 0
Baden-Wuerttemberg
Country [38] 0 0
Germany
State/province [38] 0 0
Bayern
Country [39] 0 0
Germany
State/province [39] 0 0
Brandenburg
Country [40] 0 0
Germany
State/province [40] 0 0
Niedersachsen
Country [41] 0 0
Germany
State/province [41] 0 0
Rheinland-Pfalz
Country [42] 0 0
Germany
State/province [42] 0 0
Sachsen-Anhalt
Country [43] 0 0
Germany
State/province [43] 0 0
Sachsen
Country [44] 0 0
Germany
State/province [44] 0 0
Schleswig-Holstein
Country [45] 0 0
Germany
State/province [45] 0 0
Berlin
Country [46] 0 0
Greece
State/province [46] 0 0
Athens
Country [47] 0 0
Greece
State/province [47] 0 0
Thessaloniki,
Country [48] 0 0
Greece
State/province [48] 0 0
Thessaloniki
Country [49] 0 0
India
State/province [49] 0 0
Bangalore
Country [50] 0 0
India
State/province [50] 0 0
Chennai
Country [51] 0 0
India
State/province [51] 0 0
Mumbai
Country [52] 0 0
India
State/province [52] 0 0
Pune
Country [53] 0 0
Lithuania
State/province [53] 0 0
Kaunas
Country [54] 0 0
Lithuania
State/province [54] 0 0
Vilnius
Country [55] 0 0
Mexico
State/province [55] 0 0
Jalisco
Country [56] 0 0
Mexico
State/province [56] 0 0
Morelos
Country [57] 0 0
Mexico
State/province [57] 0 0
Yucatán
Country [58] 0 0
Mexico
State/province [58] 0 0
Durango
Country [59] 0 0
New Zealand
State/province [59] 0 0
Rotorua
Country [60] 0 0
Poland
State/province [60] 0 0
Bydgoszcz
Country [61] 0 0
Poland
State/province [61] 0 0
Porabka
Country [62] 0 0
Poland
State/province [62] 0 0
Siemianowice Slaskie
Country [63] 0 0
Poland
State/province [63] 0 0
Wroclaw
Country [64] 0 0
Puerto Rico
State/province [64] 0 0
Aibonito/Puerto Rico
Country [65] 0 0
Puerto Rico
State/province [65] 0 0
Caguas
Country [66] 0 0
Puerto Rico
State/province [66] 0 0
Carolina
Country [67] 0 0
Puerto Rico
State/province [67] 0 0
Ponce
Country [68] 0 0
Puerto Rico
State/province [68] 0 0
Rio Piedras
Country [69] 0 0
Puerto Rico
State/province [69] 0 0
Trujillo Alto/Puerto Rico
Country [70] 0 0
Romania
State/province [70] 0 0
Arad
Country [71] 0 0
Romania
State/province [71] 0 0
Brasov
Country [72] 0 0
Romania
State/province [72] 0 0
Sfantu Gheorghe
Country [73] 0 0
Romania
State/province [73] 0 0
Timisoara
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Moscow
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Saint-Peterburgh
Country [76] 0 0
Russian Federation
State/province [76] 0 0
St.Petersburg
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Tomsk
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Tumen
Country [79] 0 0
South Africa
State/province [79] 0 0
Gauteng
Country [80] 0 0
South Africa
State/province [80] 0 0
Bellville
Country [81] 0 0
South Africa
State/province [81] 0 0
Parow
Country [82] 0 0
South Africa
State/province [82] 0 0
Roodepoort
Country [83] 0 0
Ukraine
State/province [83] 0 0
Dnipropetrovsk
Country [84] 0 0
Ukraine
State/province [84] 0 0
Kyiv
Country [85] 0 0
Ukraine
State/province [85] 0 0
Vinnitsa

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.