A Dose-Ranging Study of GSK189075 versus Placebo in the treatment of Type 2 Diabetes Mellitus in Subjects taking Metformin.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 0

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 <40pg/mL (<140 pmol/L can be obtained at screening, at the discretion of the investigator to confirm postmenopausal state.
5. Informed Consent: a signed and dated written consent must be obtained from the
subject before any procedures are performed.
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

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 <25 kg/m2 or >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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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