A Once-Daily Dose-Ranging Study of GSK189075 Versus Placebo In The Treatment of Type 2 Diabetes Mellitus in Treatment-Naïve Subjects

Conditions: Type 2 Diabetes Mellitus
MedDRA version: 9.1Level: LLTClassification code 10045242Term: Type II diabetes mellitus

Registration Number: EUCTR2007-001463-29-EE

Lead Sponsor: GlaxoSmithKline R&D Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 252

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 <7.5% must have a fasting fingerstick glucose ³7 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).
2. 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
3. Subjects who are 18 to 70 years of age inclusive at the time of Screening.
4. 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), or females who are post-menopausal.
All females must have a negative urine pregnancy test on the day of, and prior to randomization. Note: In questionable cases, a blood sample for follicle stimulating hormone (FSH) >40 MIU/mL and estradiol <40pg/mL (<140 pmol/L) may be obtained at screening, at the discretion of the investigator to confirm post-menopausal 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

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 <0.4 MIU/L (<0.4 MCIU/mL) or >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 <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
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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.<br>•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.<br>•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.<br>•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<br>

Secondary Outcome Measures

Name	Time	Method

Related Trials