Type 2 diabetes mellitus MedDRA version: 8.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus
Conditions
Interventions
Product Name: GSK189075
Pharmaceutical Form: Tablet
Current Sponsor code: GSK189075
Concentration unit: mg/g milligram(s)/gram
Concentration type: range
Concentration number: 100-2000
Pharmaceutical f
Sponsors
GlaxoSmithKline Research & Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the Investigator’s Brochure. Subjects eligible for enrollment in the study must meet all of the following 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 a central laboratory. 2. Subjects who are treatment naïve, or who may have taken insulin or any oral antidiabetic medications for a total of no more than 2 and 4 weeks respectively within the previous 12 months, but not at all within the 3 months prior to screening, or subjects who are newly diagnosed and treated with diet and exercise for a minimum of 8 weeks. 3. Subjects who are 18 to 70 years of age inclusive at the time of Screening. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. 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 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 for more than 4 weeks in the 12 months prior to screening or at anytime within the 3 months prior to screening. 3. 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. NYHA Class I may be included 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 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 plasma 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 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 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. 5. Pancreatic Disease • Secondary causes of diabetes: - history of chronic or acute pancreatitis 6. Renal Disease • Significant renal disease at Screening as manifested by: - Glomerular filtration rate (GFR) <60mL/min (as estima
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The present study is a dose-ranging study that will evaluate the efficacy, safety and tolerability of a range of doses of GSK189075 and pioglitazone 30mg, compared to placebo, administered as monotherapy over 12 weeks in treatment naïve subjects with Type 2 Diabetes Mellitus. ;Secondary Objective: To evaluate the safety and tolerability of a range of doses of GSK189075 and 30mg pioglitazone. • To evaluate the effect of a range of doses of GSK189075 and 30mg pioglitazone, compared to placebo, on additional glycemic/pharmacodynamic parameters in a fasted state [plasma glucose, serum insulin, serum fructosamine, serum lipid profiles] • To evaluate the effect of a range of doses of GSK189075 and 30mg pioglitazone, compared to placebo, on glycemic/pharmacodynamic profiles during a 50g oral glucose tolerance test (plasma glucose/insulin over a 2-hour period) in a sub-group of subjects. • To evaluate the effect of a range of doses of GSK189075 and 30mg pioglitazone, compared to placebo, on body weight and waist circumference. ;Primary end point(s): The primary objective is to determine the dose response and efficacy of a range of doses of GSK189075 and 30mg of pioglitazone versus placebo on the reduction of HbA1c. | — |
Countries
Bulgaria, Czech Republic, Germany, Hungary, Latvia, Lithuania
Outcome results
None listed