Type 2 Diabetes Mellitus MedDRA version: 9.1 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 R&D Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrollment in the study must meet all of the following criteria: 1. Subjects with a documented diagnosis of T2DM and HbA1c =7.0% and =9.5% measured by the central laboratory at Visit 1 and Visit 2. Note: Subjects with HbA1c 40 MIU/mL and estradiol =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 5.5 mIU/L (>5.5 MCIU/mL) at Screening. Note: Hypothyroidism treated with the same dose and regimen of thyroid hormone replacement for at least 3 months prior to Screening is allowed. •BMI of 43 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, 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 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 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. 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 manifested by: •lomerular filtration rate (GFR) <60mL/min (as calculated by Quest at Visit using the Modification of Diet in Renal Disease (MDRD) equation as follows: GFR (mL/min/1.73m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the dose response and efficacy of a range of once daily doses of GSK189075 versus placebo on the change from baseline in HbA1c.;Primary end point(s): The primary endpoint is the change from baseline (Week 0) in HbA1c at Week 12 for GSK189075 dosed once daily compared to placebo.;Secondary Objective: •To evaluate, alongside once daily dosing, the efficacy of one bid dose of GSK189075 and 30mg pioglitazone versus placebo, on the change from baseline in HbA1c. •To evaluate the safety and tolerability of a range of qd doses of GSK189075 versus placebo alongside one bid dose of GSK189075 and 30mg pioglitazone. •To evaluate the effect of a range of qd doses of GSK189075 versus placebo, and alongside one bid dose of GSK189075 and 30mg pioglitazone, on additional glycemic/PD parameters. •To evaluate the effect of a range of qd doses of GSK189075 versus placebo, and alongside one bid dose of GSK189075 and 30mg pioglitazone on body weight | — |
Countries
Czech Republic, Estonia, Germany, Greece, Hungary, Lithuania
Outcome results
None listed