Subjects between the ages of 18 and 70 years with T2DM who are diet and/or exercise treated or receiving stable metformin monotherapy will be recruited MedDRA version: 7.1 Level: LLT Classification code 10052066
Conditions
Interventions
Product Name: GW677954
Product Code: GW677954
Pharmaceutical Form: Capsule*
Current Sponsor code: GW677954
Concentration unit: mg/g milligram(s)/gram
Concentration type: range
Concentration number: 2.
Sponsors
GlaxoSmithKline R&D
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with T2DM as defined by the criteria of the ADA and/or recognized by WHO Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (American Diabetes Association, 2004), for at least 3 months preceding screening (see Section 15.3, Appendix 3:, “Diagnosis and Classification of Diabetes Mellitus"). 2. To be eligible for Randomization into the trial, a subject must satisfy all of the following glycemic criteria: • HbA1c level via central laboratory at the pre-screening visit • If HbA1c = 8.0% but = 10.0%: subject may proceed to Randomization; • If HbA1c = 7.8% but 1 year without menstrual period]); or, • If of child-bearing potential, has a negative pregnancy test at Screening (serum), at Randomization (urine) and: ? Has a male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female subject, or ? Uses double-barrier methods of contraception; condoms with the use of caps (with spermicide) and IUDs are acceptable, or ? Uses hormonal contraceptives (oral, depots, patches etc) with doublebarrier methods of contraception as outlined above, or ? Abstains from sexual intercourse, or ? Is with a same sex partner and does not participate in bisexual activities where there is any risk of pregnancy. 6. Body Mass Index (BMI): = 25 and = 40 kg/m2 and weigh at least 50 kg at Screening. 7. If subject is a smoker, must be able to abstain while in clinic at each visit. 8. Subject has given full written informed consent prior to any study related 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
Exclusion criteria: 1. Metabolic Disease including: • Diagnosis of Type 1 diabetes mellitus • Uncorrected thyroid dysfunction. • Significant weight gain or loss within the 3 months prior to Screening. 2. Previous use of insulin for treatment of hyperglycemia within 3 months of screening. 3. History of recent clinically significant cardiovascular disease including: • History or ECG evidence of prior myocardial infarction within 6 months prior to Screening. • Current unstable angina or history of unstable angina in past 6 months. • Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery that is either planned or occurred in the 6 months prior to Screening. • Clinically significant arrhythmia or valvular heart disease. • Congestive heart failure (CHF) with New York Heart Association (NYHA) Class II-IV symptoms (see Section 15.4, Appendix 4). • Blood pressure > 160/100 mmHg or resting heart rate > 100 bpm. • Has a QTc interval (Bazett’s) > 440 msec in males and > 450 msec in females at Screening. • Clinically significant ECG abnormalities which, in the opinion of the Investigator, may affect the interpretation of safety data, or which otherwise, contraindicates participation in a clinical trial with a new chemical entity. 4. History of chronic pancreatitis. 5. Familial hypercholesterolemia. 6. TGs = 800 mg/dL (8.96 mmol/L) at Screening. 7. Serum creatinine at screening > 1.4 mg/dL (124 µmol/L) for women, or > 1.5 mg/dL (133 µmol/L) for men. 8. Clinically significant anemia defined by hemoglobin concentrations <12.0 g/dL or < 120.0 g/L for males and < 11.0 g/dL or < 110.0 g/L for females. 9. History of significant co-morbid diseases 10. Documented history of hepato-biliary disease including a history of, or positive laboratory results for hepatitis at Screening, and/or clinically significant hepatic enzyme elevation including: • Any one of the following enzymes greater than 2.5 times the upper limit of normal (ULN) value at Screening 11. History of metabolic acidosis, rhabdomyolysis, myalgia, myositis or myopathy after taking statins or fibrates. 12. Any subject who has withdrawn therapy due to AEs after taking a PPAR? or a PPARa/? dual agonist, either marketed (e.g., troglitazone, rosiglitazone or pioglitazone) or under current or previous clinical investigation. 13. Signs or symptoms of myositis at Screening (or upon 1 repeat test), and/or creatinine phosphokinase (CPK) = 3.0 times ULN 14. Is currently taking or has taken any of the following medications in the 3 months prior to the pre-screening visit: • Anti-obesity agents (including fat absorption blocking agents) • St. John’s Wort • Warfarin and other oral anticoagulants (excluding aspirin and non-steroidal antiinflammatory drugs) • Digoxin • Oral or injectable corticosteroids (inhaled and intranasal steroids are acceptable) • Use of antidiabetic agents (other than metformin) in the 2 months prior to the prescreening visit. • Use of TZDs in the 3 months prior to the pre-screening visit. • Methotrexate, cyclosporine or monoclonal antibodies (e.g., alemtuzumab, gemtuzumab ozogamicin, rituximab, trastuzumab, ibritumomab, tioxetan) for rheumatoid arthritis or psoriasis. • Atypical antipsychotic medications • Antiretroviral drugs • Use of lipid lowering agents within 3 months prior to the pre-screening visit. This includes statins, fibrates, ezetimibe (Zetia), niacin and bile acid sequestrants. • Monoamine oxidase inhibitors
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate temporal changes in PD glycemic parameters, effect on fasting insulin and C-peptide levels, and on measures of insulin resistance through homeostasis model resulting from administering a range of doses of GW677954 (±metformin) in subjects with T2DM. To investigate the effects of a range of doses of GW677954 (± metformin) versus placebo (± metformin) on lipid parameters. To characterize the population PK of GW677954 (± metformin). To characterize the safety profile of GW677954 (±metformin) To investigate the effects of a range of doses of GW677954 (± metformin) versus placebo (± metformin) on biomarkers of fluid retention, cardiovascular risk, systemic inflammation, and insulin sensitivity. To characterise the safety and tolerability of GW677954 at doses of 2.5mg, 5mg,10mg and 20mg and compare with that of placebo through assessment of physical examination, vital signs, clinical laboratory tests, ophthalmic assessments and AE reporting. ;Main Objective: To evaluate the dose response and efficacy of 5 doses (2.5 mg, 5 mg, 10 mg, 15 mg and 20 mg qd) of GW677954 (± metformin) versus placebo (± metformin) on the reduction of hyperglycemia (assessed by HbA1c) after 16 weeks of dosing in subjects with T2DM;Primary end point(s): Change from baseline in fasting HbA1c levels at Week 16 | — |
Countries
Czech Republic, Latvia
Outcome results
None listed