Type II Diabetes Mellitus MedDRA version: 12.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus
Conditions
Interventions
Product Name: SRT2104
Product Code: SRT2104
Pharmaceutical Form: Capsule, hard
Current Sponsor code: SRT2104
Other descriptive name: API2104, API-2104
Concentration unit: mg milligram(s)
Concentration
Sponsors
Sirtris Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to provide written informed consent to participate in the study. 2. Ambulatory male and female subjects (of any race) with T2D within the age range of 18–65 years (inclusive) at the time of screening. 3. All female subjects must be of non-childbearing potential. For the purposes of this study, non-childbearing is defined as: • Amenorrheic for at least 12 consecutive months; menopausal status in amenorrheic females will be confirmed by demonstrating levels of follicle stimulating hormone (FSH) >40–138 mIU/mL and estradiol =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any major illness in the 3 months prior to study entry or any significant ongoing chronic medical illness not related to diabetes (e.g., recent myocardial infarction, unstable angina, stroke, or transient ischemic attack) which in the opinion of the principal investigator or medical monitor could risk subject safety or interpretation of the results. 2. Renal or liver impairment, defined as: • Serum creatinine level of = 1.4 mg/dL for females and = 1.5 mg/dL for males • Glomerular filtration rate 1.5xULN (an isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%). 3. Grade R2, M1 or higher diabetic retinopathy (according to the classification of the National Screening Committee) based on an ophthalmological examination or fundus photography performed within 3 months of the Screening Visit. 4. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of Screening. 5. A positive test for HIV antibody. 6. History of or current gastrointestinal diseases influencing drug absorption as judged by the investigator. 7. History of known cardiovascular disorder including coronary artery disease or peripheral arterial disease. 8. History of diabetic neuropathy, gastroparesis or diabetic foot. 9. Significant history of alcoholism or drug/chemical abuse, or a positive result of the urine drug/alcohol screen at the Screening Visit, or consuming more than 28 units of alcohol per week (one unit of alcohol equals about 250 mL of beer or lager, one glass of wine, or 20 mL spirits). 10. Participation in any clinical trial within 3 months prior to the first dose of investigational product in the current study. 11. History of difficulty in donating blood or accessibility of veins in left or right arm. 12. Donation or loss of blood (more than 500 mL) within 3 months prior to receiving the first dose of investigational product. 13. Use of any prescription drug therapy, with the exception of any prescription medication administered at a stable dose for at least 6 weeks prior to Screening, provided the medication is not contraindicated by the metformin label (see Appendix A for Glucophage® Summary of Product Characteristics). Subjects who are on chronic therapy with proton pump inhibitors must be able and willing to discontinue this therapy during the dosing interval of the study. 14. Use of any anti-diabetic therapy other than metformin, within 3 months of the first dose of investigational product. 15. Use of any dietary or herbal supplements within 3 weeks prior to the first dose of investigational product. 16. History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation. 17. Active neoplastic disease or history of neoplastic disease within 5 years of study entry (except for basal cell carcinoma of the skin or carcinoma in situ). 18. Increased risk of thrombosis, e.g., subjects with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To study the effects of SRT2104 vs. placebo on insulin sensitivity including hepatic and muscular insulin sensitivity. 2. To determine the safety and tolerability of 28 days of dosing with 2.0 g SRT2104 in subjects with type 2 diabetes mellitus in a fed state.;Secondary Objective: Secondary: 1. To determine the pharmacokinetics of 28 days of dosing with 2.0 g SRT2104 in subjects with type 2 diabetes mellitus in a fed state. 2. To study the effects of SRT2104 vs. placebo on energy expenditure. 3. To study the effects of SRT2104 vs. placebo on muscle histology and biomarkers of oxidative capacity. Exploratory: 1. To study the effects of SRT2104 vs. placebo on biomarkers of glucose control and inflammation. 2. To study the effects of SRT2104 vs. placebo on biological markers of bone turnover. 3. To study the effects of SRT2104 vs. placebo on biomarkers of oxidative stress.;Primary end point(s): Safety and Tolerability: Incidence of AEs and clinically significant abnormal laboratory values will be recorded based upon investigator observation and subject reporting. Safety will be monitored by reports of AEs (at all visits and telephone contacts after the first dose has been administered through 30 days after the last dose), vital sign measurements (resting pulse rate, respiration rate, temperature, and blood pressure readings), physical examinations, laboratory parameters and electrocardiograms (ECG). Concomitant medications and AEs will be recorded at every visit. Additional visits will be permitted for safety follow-up as required. Pharmacodynamic: -HEGC procedures including indirect calorimetry (Days 0, 29, 43) to study the effects of SRT2104 vs. placebo on insulin sensitivity and energy expenditure. -OGTT will be used to assess the effects of SRT2104 on insulin sensitivity (Days -1, 28, 42). During the OGTT, blood samples will be obtained prior to the administration of 75g of oral glucose, at the time of oral glucose administration, and at 30, 60, | — |
Countries
Germany
Outcome results
None listed