A Phase IIa, Randomized, Placebo-Controlled, Double-Blind Clinical Study to Assess the Safety, Tolerability and Activity of Oral SRT2104 Capsules Administered for 28 days to Subjects with Type 2 Diabetes Mellitus.
- Conditions
- Type II Diabetes MellitusMedDRA version: 12.0Level: LLTClassification code 10045242Term: Type II diabetes mellitus
- Registration Number
- EUCTR2009-016537-98-DE
- Lead Sponsor
- Sirtris Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
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 < 30 pg/mL at entry. In the event a subject's menopause status has been clearly established (for example, the subject indicates she has been amenorrheic for 10 years), but FSH and/or estradiol levels are not consistent with a post-menopausal condition, determination of subject eligibility will be at the discretion of the principal investigator with agreement of the independent medical monitor,
• At least 6 weeks post-surgical bilateral oophorectomy (with or without hysterectomy) or post tubal ligation.
4. The subject must be on stable metformin monotherapy for a minimum of 3 months prior to the Screening visit.
5. HbA1c of < 8.5%.
6. Body Mass Index (BMI) of 22–38 kg/m2 (inclusive).
7. Resting supine blood pressure (BP) < 160/90 mmHg.
8. Have a normal 12-lead electrocardiogram (ECG) or one with changes considered to be clinically insignificant on medical review and QTc intervals as defined below:
• QTcB must be <450 msec for males and <470 msec for females (based on single or average QTc value of triplicate ECGs obtained over a brief period),
• QTcB must be < 480 msec in subjects with Bundle Branch Block.
9. Comprehension of the nature and purpose of the study and able to comply with the protocol requirements.
10. Able to communicate in person and by telephone in a manner that allows all protocol procedures to be carried out safely and reliably in the opinion of the investigative site staff.
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) no
F.1.3.1 Number of subjects for this age range
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 < 80 mL.min/1.73 m2 (estimated according to Cockgroft-Gault),
• AST and ALT = 2xULN,
• alkaline phosphatase and bilirubin > 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.
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