Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Type 2 Diabetic Human Subjects
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: SRT2104; Placebo
Intervention description: SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.; Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 227.0
Sex: All
Minimum age: 30 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study is to determine the safety and tolerability of SRT2104
      (0.25, 0.5, 1.0, and 2.0 g/day) in type 2 diabetic subjects when administered once daily for
      28 consecutive days, and to characterize the pharmacokinetic profile of SRT2104 after a
      single dose and multiple administrations in type 2 diabetic subjects.

      The secondary purpose of this study is to determine the effect of SRT2104 (0.25, 0.5, 1.0,
      and 2.0 g/day) when administered once daily for 28 consecutive days on fasting blood glucose
      and insulin and post-prandial blood glucose and insulin in type 2 diabetic subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects of any race and gender within the age range of 30 to 70 years.

          2. All female subjects must be of non-child-bearing potential. For the purposes of this
             study, this is defined as the subject being amenorrheic for at least 12 consecutive
             months, or at least 6 weeks post-surgical bilateral oophorectomy with or without
             hysterectomy, or women who underwent tubal ligation. Menopausal status will be
             confirmed by demonstrating levels of follicle stimulating hormone (FSH) 40 - 138
             mIU/ml and oestradiol < 20 pg/ml at entry, unless this information is available in the
             subject's medical record. 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 oestradiol levels are not consistent with a post-menopausal
             condition, determination of subject eligibility will be at the discretion of the
             principal investigator following consultation with the sponsor and medical monitor

          3. All male subjects must agree with their partners to use double-barrier birth control
             or abstinence while participating in the study and for 12 weeks following the last
             dose of study drug.

          4. Willingness to provide written informed consent to participate in the study

          5. HbA1c ≥ 7.5 and ≤ 10.5

          6. Fasting glucose ≥ 160 and ≤ 240 mg/dL

          7. Body Mass Index (BMI) ≥ 25.0 kg/m^2 and ≤ 40.0 kg/m^2

          8. On stable metformin medication for at least 3 months (≥ 1.0 g/day) prior to Screening

          9. No prior history of HIV 1 or 2

         10. Absence of disease markers for hepatitis B & C virus

         11. Absence of significant disease or clinically significant abnormal laboratory values on
             the laboratory evaluations, medical history or physical examination during the
             screening; normal end organ function

         12. Have a normal 12-lead ECG or one with abnormality considered to be clinically
             insignificant

         13. Have a normal chest X-ray (P. A. View) or one with abnormality considered to be
             clinically insignificant

         14. Comprehension of the nature and purpose of the study and compliance with the
             requirement of the entire protocol

        Exclusion Criteria:

          1. Any major illness in the past three months or any significant ongoing chronic medical
             illness not related to diabetes

          2. Renal or liver impairment, defined as serum creatinine level of ≥ 1.4 mg/dL for
             females and ≥ 1.5 mg/dL for males, and greater than two times the upper limit of
             normal for liver enzymes, respectively.

          3. History of or current gastro-intestinal diseases influencing drug absorption, except
             for appendectomy

          4. History, within 3 years, of drug abuse (including Benzodiazepines, opioids,
             amphetamine, cocaine, and THC)

          5. History of alcoholism (more than two years), moderate drinkers (more than three drinks
             per day) or having consumed alcohol within 48 hrs prior to dosing [one drink is equal
             to one unit of alcohol (one glass wine, half pint beer, one measure of spirit)]

          6. Participation in any clinical trial within the past three months

          7. History of difficulty in donating blood or accessibility of veins in left or right arm

          8. Donation of blood (one unit or 350 ml) within three months prior to receiving the
             first dose of test material

          9. Use of any prescription drug therapy, with 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

         10. Use of any alternate anti-diabetic therapy, except metformin, within three months of
             enrollment