Type 2 Diabetes Mellitus MedDRA version: 8.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus
Conditions
Interventions
Product Name: GSK189075
Product Code: GSK189075
Pharmaceutical Form: Tablet
Current Sponsor code: GSK189075
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: -50
Phar
Sponsors
GlaxoSmithKline Research & Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with a documented diagnosis of T2DM and have an HbA1c level at Visits 1 and 2 of =7.5% and =9.5% as measured by the central laboratory. 2. Subjects previously on a maximum effective dose of metformin monotherapy (=1500mg total daily dose). Subjects must have been on the same dose, formulation and regimen of metformin for at least 3 months (i.e., 12 weeks) prior to Screening. 3. Subjects who are 18 to 70 years of age inclusive at the time of Screening. 4. Eligible females must be of non-childbearing potential (i.e., females regardless of age who are surgically sterile (i.e., documented total hysterectomy or bilateral oophorectomy) or females who are post-menopausal (i.e., no menstrual period for a minimum of 12 consecutive months). All females must have a negative urine pregnancy test on the day of, and prior to randomization. • In questionable post-menopausal cases, a blood sample for follicle stimulating hormone (FSH) >40 MIU/mL and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Metabolic Disease • Diagnosis of Type 1 diabetes mellitus. • History of ketoacidosis and/or lactic acidosis 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 40 kg/m2. • Significant weight gain or loss (as defined as >5% of total body weight) in the 3 months prior to Screening. 2. Diabetic Medication • Has taken insulin for more than 2 weeks in the 12 months prior to screening or at any time within the 3 months prior to screening. • Has taken any oral anti-diabetic medication, apart from metformin, for more than 4 weeks in the 12 months prior to screening or at anytime within the 3 months prior to screening. • Has other concurrent condition that would contraindicate the use of metformin or a known or suspected hypersensitivity to metformin or any of its components 3. Cardiovascular Disease • Recent history (within the preceding 6 months) 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. . - 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 3 month prior to Screening. - 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). - 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 (TG) =4.56mmol/L (400mg/dL) 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 3 months prior to Screening. Niacin and bile acid sequestrants are prohibited. 4. 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. 5. Pancreatic Disease • Secondary causes of diabetes: - history of chronic or acute pancreatitis 6. Renal Disease • Significant renal disease at Screening as manifes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the dose response and efficacy of a range of once daily doses of GSK189075 in combination with metformin, versus metformin alone, on the change from baseline in HbA1c.;Primary end point(s): Primary endpoint is change from baseline (Week 0) in HbA1c at week 12.;Secondary Objective: An important supportive objective to the primary is to evaluate, alongside qd dosing, the efficacy of a range of twice daily doses of GSK189075 in combination with metformin versus metformin alone on the change from baseline in HbA1c. Secondary objectives also include comparison of the effects of therapy with GSK189075 dosed once or twice daily in combination with metformin versus metformin alone on safety and tolerability; additional markers of glycemic control; glycemic and pharmacodynamic profiles during a 2-hour oral glucose tolerance test; body weight and waist circumference; lipids; 24-hour ambulatory blood pressure; population pharmacokinetics, and self-reported outcomes of hunger and satiety, thirst, frequency and bother of micturition and nocturia. | — |
Countries
Belgium, Netherlands
Outcome results
None listed