Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Type 2 Diabetic Human Subjects

• Sponsor: Sirtris, a GSK Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00937326
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 227
• Locations: 61
• Arms: 5
• Actual Duration (Months): 13
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: SRT2104; Drug: Placebo	Phase 2

Detailed Description

Study Objectives

Primary:

1. 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.

2. To characterize the pharmacokinetic profile of SRT2104 (0.25, 0.5, 1.0, and 2.0 g/day) after a single dose and multiple administrations in type 2 diabetic subjects.

Secondary:

1. 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.

Study Design:

Prospective, multi-center, clinical study of SRT2104 administered orally once daily for 28 consecutive days; randomized, placebo-controlled, double-blind, multiple-dose, inpatient/outpatient study to assess the safety and pharmacokinetics (PK) of SRT2104 in type 2 diabetic male and female subjects on an existing, stable, background metformin therapy. Approximately 225 subjects aged 30-70, who fulfill the inclusion/exclusion criteria, will be enrolled in this study to ensure completion of forty (40) evaluable subjects within each of five dosing groups. Subjects will be evenly randomized to receive SRT2104 at one of five doses, placebo (A), 0.25 g/day (B), 0.5 g/day (C), 1.0 g/day (D), or 2.0 g/day (E), once a day for 28 consecutive days, approximately 15 minutes following consumption of a standardized meal. Subjects will remain on a fixed dose of test material for all dosing days in the study.

Subjects will sign the informed consent form at the Screening Visit, and will undergo screening assessments over a 2-day period to verify eligibility for the study. If eligible and willing to participate, subjects will return to the clinic within 21 days of the Screening Visit to participate in the dosing phase of the study. Subjects will be randomized to receive SRT2104 or placebo, and will be required to stay overnight at the study center on Day -1 and Day 27 to gather required PK samples and to assess safety on Day 1 and Day 28 respectively. In addition, subjects will be asked to return to the study center on Days 2 and 29; for three interim weekly safety assessments (on Days 8, 15, 22); and for an End of Study safety assessment 7 days after they complete the 28-day dosing period. A follow-up safety call will be made to each subject 30 days following their final dose of SRT2104 or placebo.

Study Design

• Study Type: Interventional
• Actual Enrollment: 227 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Placebo-Controlled, Double-Blind, Multiple-Dose Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Type 2 Diabetic Human Subjects
• Actual Study Start Date: Aug 19, 2009
• Actual Primary Completion Date: Sep 18, 2010
• Actual Study Completion Date: Sep 18, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo The Placebo treatment group will be administered eight placebo capsules per day. Placebo will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, approximately 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.	Drug: Placebo; Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
Active Comparator: Arm1 - 0.25g The 0.25g SRT2104 treatment group will be administered one SRT2104 capsules with 7 placebo capsules, for a total of 8 capsules per day. 0.25g SRT2104 will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.	Drug: SRT2104; SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.; Drug: Placebo; Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
Active Comparator: Arm2 - 0.5g The 0.5g SRT2104 treatment group will be administered two SRT2104 capsules with 6 placebo capsules, for a total of 8 capsules per day. 0.5g SRT2104 will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.	Drug: SRT2104; SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.; Drug: Placebo; Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
Active Comparator: Arm3 - 1g The 1g SRT2104 treatment group will be administered four SRT2104 capsules with four placebo capsules, for a total of 8 capsules per day. 1g SRT2104 will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.	Drug: SRT2104; SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.; Drug: Placebo; Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
Active Comparator: Arm4 - 2g The 2g SRT2104 treatment group will be administered eight SRT2104 capsules per day. 2g SRT2104 will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.	Drug: SRT2104; SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), AE Related to Study Medication, AE Leading to Discontinuation and Fatal AE of Death [Up to Follow-up (58 days)]

   An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. AE's were classified as related to the study medication, based on the investigator's judgment.

2. Number of Participants With AE by Intensity of Mild, Moderate and Severe [Up to Follow-up (58 days)]

   Intensity for each AE was categorized as mild, moderate and severe. Mild was defined as awareness of sign or symptom, but easily tolerated; moderate was defined as discomfort enough to cause interference with normal daily activities; severe was defined as inability to perform normal daily activities.

3. Mean Change From Baseline in Weight Over Time [Baseline (Day 1) and up to Day 35]

   Participant's body weight was assessed in the beginning of the study (at Day 1) and at the end of the study (Day 28 and Day 35). The clinical staff was instructed to use calibrated scales for weight measurement. The same scale was used at the clinical site for all participants at each specified time point during the study. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28 and Day 35) values.

4. Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time [Baseline (Day 1, pre-dose) and up to Day 35]

   Vital sign assessment of SBP and DBP was done at Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose), Day 2 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 8 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 15 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 22 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 27, Day 28 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose) and Day 35. A window of plus or minus 5 minutes was allowed during the active treatment visit vital sign assessments. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1, Day 2, Day 8, Day 15, Day 22, Day 27, Day 28 and Day 35) values.

5. Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time [Baseline (Day 1, pre-dose) and up to Day 35]

   Vital sign assessment of HR was done at Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose), Day 2 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 8 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 15 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 22 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 27, Day 28 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose) and Day 35. A window of plus or minus 5 minutes was allowed during the active treatment visit vital sign assessments. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1, Day 2, Day 8, Day 15, Day 22, Day 27, Day 28 and Day 35) values.

6. Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time [Baseline (Day 1, pre-dose) and up to Day 35]

   Vital sign assessment of RR was done at Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose), Day 2 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 8 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 15 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 22 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 27, Day 28 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose) and Day 35. A window of plus or minus 5 minutes was allowed during the active treatment visit vital sign assessments. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1, Day 2, Day 8, Day 15, Day 22, Day 27, Day 28 and Day 35) values.

7. Change From Baseline in Vital Sign Parameter of Temperature Over Time [Baseline (Day 1, pre-dose) and up to Day 35]

   Vital sign assessment of temperature was done at Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose), Day 2 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 8 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 15 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 22 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 27, Day 28 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose) and Day 35. A window of plus or minus 5 minutes was allowed during the active treatment visit vital sign assessments. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1, Day 2, Day 8, Day 15, Day 22, Day 27, Day 28 and Day 35) values.

8. Change From Baseline in Electrocardiogram (ECG) Values Over Time [Baseline (Day 1, pre-dose) and up to Day 35]

   12-lead ECG was obtained in the rested state. Participants lied in supine position with ECG leads on for at least 5 minutes prior to ECG recording. The ECG was performed at Day 1 (pre-dose and post-dose), Day 8, Day 15, Day 22, Day 28 (pre-dose and pre-dose) and Day 35, and included the assessment of PR interval, QRS interval, QT interval and QTc interval. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1 [post-dose], Day 8, Day 15, Day 22, Day 28 and Day 35) values.

9. Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time [Baseline (Day 1) and up to Day 35]

   Assessment for basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and white blood cell (WBC) count were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

10. Change From Baseline in Hematology Parameter of Red Blood Cell (RBC) Count Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for RBC count was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

11. Change From Baseline in Hematology Parameter of Hematocrit Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for hematocrit was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

12. Change From Baseline in Hematology Parameter of Hemoglobin Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for hemoglobin was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

13. Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for mean corpuscular hemoglobin was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

14. Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Concentration Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for mean corpuscular hemoglobin concentration was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

15. Change From Baseline in Hematology Parameter of Mean Corpuscular Volume Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for mean corpuscular volume was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

16. Change From Baseline in Coagulation Parameters of Activated Partial Thromplastin Time (aPTT) and Prothrombin Time (PT) Over Time [Baseline (Day 1), Day 28 and Day 35]

    Assessment for aPTT and PT were performed on Day 1, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28 and Day 35) values.

17. Change From Baseline in Coagulation Parameter of International Normalized Ratio Over Time [Baseline (Day 1), Day 28 and Day 35]

    Assessment for international normalized ratio was performed on Day 1, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28 and Day 35) values.

18. Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for ALT, AST, ALP, creatinine phosphokinase and LDH were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

19. Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for bicarbonate, BUN, calcium, chloride, magnesium, phosphate, potassium and sodium were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

20. Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for direct bilirubin, indirect bilirubin, serum creatinine, total bilirubin and uric acid were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

21. Change From Baseline in Chemistry Parameter of Lipid Profile Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for lipid profile was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. The parameters included high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol and triglycerides. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

22. Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time [Baseline (Day 1) and up to Day 35]

    Assessment for albumin and total protein were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

23. Change From Baseline in Urinalysis Parameter of Specific Gravity Over Time [Baseline (Day 1) and up to Day 35]

    Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

24. Change From Baseline in Urinalysis Parameter of pH Over Time [Baseline (Day 1) and up to Day 35]

    Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessment was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

25. Area Under Plasma Concentration Curve From Time 0 to Last Measurable Time Point (AUC 0-t), From Time 0 to Infinity (AUC 0-infinity) and From Time 0 to Trough Concentration (AUC 0-τ) of SRT2104 on Day 1 and Day 28 [Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28)]

    The pre-dose blood samples were collected within one hour prior to study medication administration. The post-dose blood samples were collected within 2 minutes of the scheduled time. AUC values reported in the analysis of AUC 0-infinity of Day 28 versus Day 1 included AUC 0-infinity on Day 1 and AUC 0-τ on Day 28. Participants fasted for at least 10 hour overnight on Day 1, 2 and 29. The AUC 0-t was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. AUC0-infinity was estimated by linear trapezoidal rule and was sum of the AUC0-t and extrapolated to infinity by dividing the estimated last measurable plasma concentration by elimination rate constant lambda z. Where lambda z is the terminal phase rate constant estimated by linear regression analysis of the log10 transformed concentration-time data after each single dose. The AUC0-infinity was the sum of the estimated and extrapolated parts.

26. Observed Maximum Plasma Concentration (Cmax) of SRT2104 at Day 1 and Day 28 [Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)]

    Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. On Day 1, Day 2 and Day 29, participants fasted for at least 10 hour overnight. The post-dose sample was collected within 2 minutes of the scheduled time. The first occurrence of the Cmax was determined directly from the raw concentration-time data.

27. Time to Cmax (Tmax) at Day 1 and Day 28 [Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)]

    Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. The post-dose sample was collected within 2 minutes of the scheduled time. The time at which Cmax was observed was determined directly from the raw concentration-time data.

28. Terminal Elimination Half Life (T1/2) of SRT2104 at Day 1 and Day 28 [Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)]

    Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. The post-dose sample was collected within 2 minutes of the scheduled time. On Day 1 Day 2 and Day 29, participants fasted for at least 10 hour overnight. The t1/2 was obtained as the ratio of ln2/λz, where λz is the terminal phase rate constant estimated by linear regression analysis of the concentration-time data.

29. Apparent Total Clearance of SRT2104 From Plasma After Oral Administration (CL/F) on Day 1 and Day 28 [Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)]

    Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. The post-dose sample was collected within 2 minutes of the scheduled time. On Day 1 Day 2 and Day 29, participants fasted for at least 10 hour overnight.

30. Apparent Volume of Distribution After Oral Administration (Vd/F) at Day 1 and Day 28 [Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)]

    Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. The post-dose sample was collected within 2 minutes of the scheduled time. On Day 1 Day 2 and Day 29, participants fasted for at least 10 hour overnight.

Secondary Outcome Measures

1. Mean Fasting Plasma Glucose (FPG) Levels Over Time [Up to Day 35]

   The assessments were done at Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35 weekly at central laboratory. The analysis was reported for Day 8, Day 15, Day 22, Day 28 and Day 35.

2. Change From Baseline in FPG Levels Over Time [Baseline (Day 1) and up to Day 35]

   The assessments were done at Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35 weekly at central laboratory. Baseline was defined as the assessment done on Day 1. The analysis was reported for Day 8, Day 15, Day 22, Day 28 and Day 35. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

3. Mean Fasting Plasma Insulin (FPI) Levels Over Time [Up to Day 35]

   The assessments were done at Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35 weekly at central laboratory. The analysis was reported for Day 8, Day 15, Day 22, Day 28 and Day 35.

4. Change From Baseline in FPI Over Time [Baseline (Day 1) and up to Day 35]

   The assessments were done at Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35 weekly at central laboratory. Baseline was defined as the assessment done on Day 1. The analysis was reported for Day 8, Day 15, Day 22, Day 28 and Day 35. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.

5. Mean Post-prandial Glucose (PPG) and Post-prandial Insulin (PPI) Levels at Day 28 [Day 28]

   The assessment of PPG and PPI was performed on Day 28 at 30 minutes, 60 minutes and 2 hour after the participant consumed the standardized meal (morning breakfast).

6. Change From Baseline in PPG and PPI Levels at Day 28 [Baseline (Day 1) and Day 28]

   The assessment of PPG and PPI was performed at 30 minutes, 60 minutes and 2 hour after the participant consumed the standardized meal (morning breakfast) on Day 1 and Day 28. Baseline for PPG was defined as the assessment value of FPG done on Day 1 and Baseline for PPI was defined as the assessment value of FPI done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (30 min, 60 min and 2 h at Day 28) values.

7. Mean Glycosylated Hemoglobin A (HbA1c) Levels on Day 28 [Day 28]

   The sample for HbA1c assessment was collected on Day 28. HbA1c is used to show how well their diabetes is being controlled in participants with diabetes. The HbA1c test gives the average blood glucose levels over the pervious two to three months.

8. Change From Baseline in HbA1c Levels at Day 28 [Baseline (Day 1) and Day 28]

   HbA1c is used to show how well their diabetes is being controlled in participants with diabetes. The HbA1c test gives the average blood glucose levels over the pervious two to three months. The sample for HbA1c assessment was collected on Day 1 and Day 28. Baseline value was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28) value.

9. AUC From Time 0 to 1 h (AUC 0-1) and AUC From Time 0 to 2 h (AUC 0-2) for PPG and PPI at Day 1 and Day 28 [Day 1 (30 minutes, 60 minutes and 2 hour) and Day 28 (30 minutes, 60 minutes and 2 hour)]

   The assessment of PPG and PPI was performed at 30 minutes, 60 minnutes and 2 hour after the participant consumed the standardized meal (morning breakfast) on Day 1 and Day 28. AUC with respect to these time interval was calculated using the linear trapezoidal rule by the sum of the areas between each chronological pair of assessments (using observed times) for PPG and PPI.

10. Mean Fructosamine Levels at Day 1 and Day 28 [Day 1 and Day 28]

    Fructosamine (a glycated protein) level enables assessment of long-term glycemic control in participants with diabetes mellitus. The blood samples for fructosamine assessment was obtained at Day 1 and Day 28.

11. Change From Baseline in Fructosamine Levels at Day 28 [Baseline (Day 1) and Day 28]

    Fructosamine (a glycated protein) level enables assessment of long-term glycemic control in participants with diabetes mellitus. The blood samples for fructosamine assessment was obtained at Day 1 and Day 28. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28) value.

12. Mean Homeostatic Model Assessment-insulin Resistance (HOMA-IR) at Day 1 and Day 28 [Day 1 and Day 28]

    HOMA-IR was derived from FPG and FPI as: FPI (micro units [mU]/mL)*FPG (mmol per liter) divided by 22.5. HOMA-IR was calculated from the Day 1 and Day 28 FPG and FPI values at Day 1 and Day 28.

13. Change From Baseline in HOMA-IR at Day 28 [Baseline (Day 1) and Day 28]

    HOMA-IR was derived from FPG and FPI as: FPI (mU/mL)*FPG (mmol per liter) divided by 22.5. HOMA-IR was calculated from the Day 1 and Day 28 FPG and FPI values at Day 1 and Day 28. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28) value.

14. Mean HOMA-percentage Cell Beta Function at Day 1 and Day 28 [Day 1 and Day 28]

    HOMA-percentage cell beta function was derived from FPG and FPI as: 20*FPI (mU/mL) divided by FPG (mmol per liter) minus 3.5. HOMA-percentage cell beta function was calculated from the Day 1 and Day 28 FPG and FPI values at Day 1 and Day 28.

15. Change From Baseline in HOMA-percentage of Beta Cell Function at Day 28 [Baseline (Day 1) and Day 28]

    HOMA-percentage cell beta function was derived from FPG and FPI as: 20*FPI (mU/mL) divided by FPG (mmol per liter) minus 3.5. HOMA-percentage cell beta function was calculated from the Day 1 and Day 28 FPG and FPI values at Day 1 and Day 28. Baseline was defined as assessment done on Day 1. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28) value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Byala		Bulgaria	7100
2	GSK Investigational Site	Dimitrovgrad		Bulgaria	6400
3	GSK Investigational Site	Haskovo		Bulgaria	6300
4	GSK Investigational Site	Pleven		Bulgaria	5800
5	GSK Investigational Site	Plovdiv		Bulgaria	4000
6	GSK Investigational Site	Plovdiv		Bulgaria	4002
7	GSK Investigational Site	Ruse		Bulgaria	7002
8	GSK Investigational Site	Sofia		Bulgaria	1407
9	GSK Investigational Site	Sofia		Bulgaria	1431
10	GSK Investigational Site	Tallinn		Estonia	10138
11	GSK Investigational Site	Tallinn		Estonia	10617
12	GSK Investigational Site	Tallinn		Estonia	13419
13	GSK Investigational Site	Balantonfured		Hungary	8230
14	GSK Investigational Site	Eger		Hungary	3300
15	GSK Investigational Site	Gyula		Hungary	5701
16	GSK Investigational Site	Kecskemet		Hungary	6000
17	GSK Investigational Site	Sopron		Hungary	9400
18	GSK Investigational Site	Szekszard		Hungary	7100
19	GSK Investigational Site	Zalaegerszeg		Hungary	8900
20	GSK Investigational Site	Cieszyn		Poland	43-400
21	GSK Investigational Site	Lubin		Poland	20-090
22	GSK Investigational Site	Lubin		Poland	59-301
23	GSK Investigational Site	Pulawy		Poland	24-100
24	GSK Investigational Site	Radzymin		Poland	05-250
25	GSK Investigational Site	Ruda Slaska		Poland	41-709
26	GSK Investigational Site	Slupsk		Poland	76-200
27	GSK Investigational Site	Tychy		Poland	43-100
28	GSK Investigational Site	Warszawa		Poland	04-141
29	GSK Investigational Site	Bacau		Romania	600114
30	GSK Investigational Site	Braila		Romania	810249
31	GSK Investigational Site	Buzau		Romania	120257
32	GSK Investigational Site	Constanta		Romania	900591
33	GSK Investigational Site	Oradea		Romania	410169
34	GSK Investigational Site	Ploiesti		Romania	100097
35	GSK Investigational Site	Timisoara		Romania	300456
36	GSK Investigational Site	Barnaul		Russian Federation	656024
37	GSK Investigational Site	Kemerovo		Russian Federation	650061
38	GSK Investigational Site	Kemerovo		Russian Federation	650099
39	GSK Investigational Site	Moscow		Russian Federation	115 280
40	GSK Investigational Site	Moscow		Russian Federation	119881
41	GSK Investigational Site	Moscow		Russian Federation	121069
42	GSK Investigational Site	Moscow		Russian Federation	127486
43	GSK Investigational Site	Moscow		Russian Federation	129110
44	GSK Investigational Site	Novosibirsk		Russian Federation	630068
45	GSK Investigational Site	Novosibirsk		Russian Federation	630090
46	GSK Investigational Site	Rostov-on-Don		Russian Federation	344022
47	GSK Investigational Site	St. Petersburg		Russian Federation	190103
48	GSK Investigational Site	St.-Petersburg		Russian Federation	194354
49	GSK Investigational Site	Tumen		Russian Federation	625023
50	GSK Investigational Site	Ufa		Russian Federation	450071
51	GSK Investigational Site	Yaroslavl		Russian Federation	150062
52	GSK Investigational Site	Kharkiv		Ukraine	61022
53	GSK Investigational Site	Mykolaiv		Ukraine	54003
54	GSK Investigational Site	Simferopol		Ukraine	95017
55	GSK Investigational Site	Ternopil		Ukraine	46001
56	GSK Investigational Site	Vinnitsa		Ukraine	21010
57	GSK Investigational Site	Zaporizhzhya		Ukraine	69001
58	GSK Investigational Site	Zaporizhzhya		Ukraine	69035
59	GSK Investigational Site	Birmingham		United Kingdom	B9 5SS
60	GSK Investigational Site	London		United Kingdom	SE 1 9RT
61	GSK Investigational Site	Newport		United Kingdom	PO30 5TG

Sponsors and Collaborators

• Sirtris, a GSK Company
• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: Sirtris, a GSK Company
• ClinicalTrials.gov Identifier: NCT00937326
• Other Study ID Numbers: 113160
• First Posted: Jul 13, 2009
• Last Update Posted: Jul 13, 2018
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2

Study Results

Participant Flow

Recruitment Details	The study was planned on 225 male and female participants with type 2 diabetes (T2D) on an existing, stable, background metformin therapy, aged 30 to 70 years, at 45 centers of Bulgaria (7), Estonia (1), Hungary (4), Poland (4), Romania (6), Russia (13), United Kingdom (3) and Ukraine (7) from 19 August 2009 to 18 September 2010.
Pre-assignment Detail	Out of 527 participants screened, 227 with glycosylated hemoglobin A (HbA1c) of >=7.5% and <= 10.5% and a fasting glucose (FG) >=160 and <=240 milligram per deciliter (mg/dL) were randomized in 1:1:1:1:1 to oral dose of placebo or any one of 4 doses of SRT2104 (0.25, 0.5, 1.0 or 2.0 gram per day [g/day]), once a day for 28 consecutive days.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 minutes (min) following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Period Title: Overall Study
STARTED	46	45	46	45	45
COMPLETED	43	38	42	40	40
NOT COMPLETED	3	7	4	5	5

Baseline Characteristics

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day	Total
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Total of all reporting groups
Overall Participants	46	45	46	45	45	227
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.8 (8.40)	58.2 (8.04)	57.7 (9.00)	57.3 (8.95)	55.9 (9.03)	57.0 (8.67)
Sex: Female, Male (Count of Participants)
Female	28 60.9%	22 48.9%	28 60.9%	30 66.7%	18 40%	126 55.5%
Male	18 39.1%	23 51.1%	18 39.1%	15 33.3%	27 60%	101 44.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	1 2.2%	1 0.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 2.2%	0 0%	0 0%	0 0%	0 0%	1 0.4%
White	45 97.8%	45 100%	46 100%	45 100%	44 97.8%	225 99.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), AE Related to Study Medication, AE Leading to Discontinuation and Fatal AE of Death
Description	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. AE's were classified as related to the study medication, based on the investigator's judgment.
Time Frame	Up to Follow-up (58 days)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAF) Population was defined as all participants who received at least one dose of any test material during the study.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Any AE	11 23.9%	15 33.3%	19 41.3%	11 24.4%	15 33.3%
Any SAE	0 0%	1 2.2%	1 2.2%	0 0%	0 0%
Any AE related to study medication	0 0%	1 2.2%	0 0%	1 2.2%	1 2.2%
Any AE leading to discontinuation	0 0%	3 6.7%	2 4.3%	1 2.2%	2 4.4%
Any fatal AE of death	0 0%	0 0%	1 2.2%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day in number of participants with any AE.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4816
	Comments	No adjustments for covariates were made.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day in number of participants with any AE.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1147
	Comments	No adjustments for covariates were made.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day in number of participants with any AE.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	No adjustments for covariates were made.
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day in number of participants with any AE.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4816
	Comments	No adjustments for covariates were made.
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	Number of Participants With AE by Intensity of Mild, Moderate and Severe
Description	Intensity for each AE was categorized as mild, moderate and severe. Mild was defined as awareness of sign or symptom, but easily tolerated; moderate was defined as discomfort enough to cause interference with normal daily activities; severe was defined as inability to perform normal daily activities.
Time Frame	Up to Follow-up (58 days)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Mild AE	8 17.4%	10 22.2%	11 23.9%	8 17.8%	9 20%
Moderate AE	7 15.2%	6 13.3%	12 26.1%	5 11.1%	7 15.6%
Severe AE	0 0%	1 2.2%	1 2.2%	0 0%	0 0%

3. Primary Outcome

Title	Mean Change From Baseline in Weight Over Time
Description	Participant's body weight was assessed in the beginning of the study (at Day 1) and at the end of the study (Day 28 and Day 35). The clinical staff was instructed to use calibrated scales for weight measurement. The same scale was used at the clinical site for all participants at each specified time point during the study. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 28	-0.17 (1.25)	-0.81 (2.21)	-1.25 (2.06)	-0.56 (1.68)	-1.54 (3.82)
Day 35	-0.40 (1.39)	-0.91 (2.90)	-1.32 (1.89)	-0.86 (1.78)	-2.74 (7.27)

4. Primary Outcome

Title	Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
Description	Vital sign assessment of SBP and DBP was done at Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose), Day 2 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 8 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 15 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 22 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 27, Day 28 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose) and Day 35. A window of plus or minus 5 minutes was allowed during the active treatment visit vital sign assessments. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1, Day 2, Day 8, Day 15, Day 22, Day 27, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1, pre-dose) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
SBP, Day 1, 15 minutes	-1.49 (9.45)	1.30 (8.36)	0.36 (5.27)	-0.88 (5.13)	-0.24 (5.45)
SBP, Day 1, 30 minutes	-1.44 (7.16)	0.02 (6.24)	1.36 (5.59)	-0.95 (6.05)	-1.10 (6.80)
SBP, Day 1, 1 hour	-2.51 (10.03)	-0.81 (6.78)	-0.02 (6.33)	-1.83 (5.68)	-1.40 (7.11)
SBP, Day 1, 2 hour	-1.60 (10.25)	-0.51 (5.51)	-1.45 (7.30)	-1.64 (7.51)	-2.93 (7.77)
SBP, Day 1, 3 hour	-2.33 (10.78)	-1.14 (5.58)	-1.98 (7.22)	-1.33 (6.61)	-2.71 (7.61)
SBP, Day 1, 4 hour	-3.51 (11.38)	-1.53 (6.52)	-0.86 (7.33)	-3.71 (8.71)	-2.74 (8.16)
SBP, Day 1, 8 hour	-4.07 (9.19)	-0.93 (7.06)	0.39 (6.96)	-2.26 (8.50)	-1.45 (7.23)
SBP, Day 1, 12 hour	-3.02 (12.64)	0.02 (7.63)	0.02 (7.78)	-0.83 (8.30)	0.81 (8.03)
SBP, Day 1, 24 hour	-1.41 (6.11)	0.14 (4.75)	-0.44 (5.68)	-0.02 (5.26)	-1.39 (6.21)
SBP, Day 2, pre-dose	-1.64 (8.49)	-0.30 (6.49)	-1.05 (6.85)	-0.31 (6.79)	-2.50 (7.70)
SBP, Day 2, 5 minutes	-2.81 (9.74)	-0.47 (7.07)	-0.54 (5.78)	-0.40 (6.67)	-1.45 (8.00)
SBP, Day 2, 30 minutes	-3.13 (8.79)	-0.43 (6.81)	-1.47 (5.99)	-2.00 (6.88)	-1.38 (6.88)
SBP, Day 2, 1 hour	-3.22 (8.67)	-0.48 (6.24)	-1.34 (7.33)	-1.32 (7.67)	-0.88 (7.38)
SBP, Day 8, pre-dose	-2.83 (10.96)	-1.63 (6.22)	0.42 (10.22)	0.68 (9.93)	-1.36 (8.57)
SBP, Day 8, 5 minutes	-3.67 (10.94)	-1.47 (5.50)	1.00 (7.76)	1.20 (9.63)	-0.73 (7.93)
SBP, Day 8, 30 minutes	-1.72 (9.10)	-0.85 (6.48)	-0.29 (7.82)	0.33 (9.31)	-1.92 (8.31)
SBP, Day 8, 1 hour	-2.24 (10.22)	-1.00 (5.68)	-1.71 (7.80)	-2.75 (10.30)	-1.87 (7.66)
SBP, Day 15, pre-dose	-2.77 (10.88)	-0.43 (7.22)	0.65 (8.22)	0.76 (9.66)	0.03 (8.50)
SBP, Day 15, 5 minutes	-4.16 (12.17)	-1.15 (6.47)	0.69 (8.67)	-0.27 (7.89)	-1.18 (8.75)
SBP, Day 15, 30 minutes	-3.56 (10.28)	-0.61 (8.31)	0.03 (8.98)	-1.83 (9.16)	-1.97 (8.36)
SBP, Day 15, 1 hour	-3.50 (10.25)	-0.24 (6.43)	-0.54 (7.27)	-0.98 (9.96)	-1.50 (7.91)
SBP, Day 22, pre-dose	-2.07 (9.75)	-0.67 (8.49)	-0.53 (8.71)	-0.08 (9.92)	0.08 (10.59)
SBP, Day 22, 5 minutes	-3.77 (11.97)	-1.46 (6.87)	-0.57 (6.72)	0.08 (9.18)	-1.18 (9.91)
SBP, Day 22, 30 minutes	-3.03 (10.05)	-1.56 (6.64)	-1.77 (6.69)	-1.10 (9.78)	-2.05 (8.73)
SBP, Day 22, 1 hour	-3.39 (9.31)	-1.64 (6.68)	-1.51 (8.29)	-0.85 (9.57)	-2.24 (9.37)
SBP, Day 27	-2.91 (9.87)	-0.49 (7.74)	-0.48 (8.68)	0.15 (9.04)	-1.05 (8.69)
SBP, Day 28, pre-dose	-2.60 (10.39)	-0.05 (7.17)	-1.10 (9.35)	0.70 (9.92)	-0.90 (8.04)
SBP, Day 28, 15 minutes	-4.58 (11.88)	-1.86 (7.11)	-1.21 (9.99)	-0.63 (9.60)	-1.56 (8.34)
SBP, Day 28, 30 minutes	-4.07 (11.26)	-2.65 (6.47)	-1.69 (9.70)	-1.43 (9.09)	-2.44 (8.02)
SBP, Day 28, 1 hour	-4.74 (11.62)	-2.78 (6.77)	-1.26 (8.40)	-2.13 (9.24)	-3.85 (7.35)
SBP, Day 28, 2 hour	-5.07 (12.33)	-2.65 (6.63)	-0.98 (9.10)	-2.90 (7.32)	-3.21 (8.70)
SBP, Day 28, 3 hour	-4.33 (11.33)	-2.84 (6.24)	-2.60 (8.32)	-2.03 (8.98)	-1.79 (9.01)
SBP, Day 28, 4 hour	-4.28 (11.36)	-3.16 (6.86)	-2.21 (7.89)	-3.48 (9.35)	-2.21 (7.56)
SBP, Day 28, 8 hour	-4.51 (12.32)	-2.11 (7.12)	-1.45 (8.96)	-2.83 (9.35)	-1.85 (9.02)
SBP, Day 28, 12 hour	-4.95 (11.61)	-0.97 (6.73)	-2.14 (8.08)	-0.75 (8.48)	-0.82 (9.52)
SBP, Day 28, 24 hour	-4.05 (11.72)	-1.42 (6.82)	-1.45 (7.42)	-0.08 (8.02)	-3.00 (8.28)
SBP, Day 35	-4.44 (12.39)	-2.83 (7.47)	-0.70 (8.05)	0.37 (8.66)	-0.51 (9.88)
DBP, Day 1, 15 minutes	-1.12 (6.71)	-0.42 (5.13)	-1.41 (6.44)	-0.38 (5.96)	-1.55 (5.67)
DBP, Day 1, 30 minutes	-1.37 (5.98)	-1.05 (4.35)	-1.73 (5.87)	-0.29 (5.75)	-1.88 (5.87)
DBP, Day 1, 1 hour	-2.70 (6.65)	-1.09 (5.12)	-1.89 (5.91)	-0.95 (5.64)	-2.83 (5.33)
DBP, Day 1, 2 hour	-0.74 (7.50)	-1.26 (6.08)	-1.66 (5.69)	-0.45 (5.32)	-3.55 (6.01)
DBP, Day 1, 3 hour	-1.74 (6.08)	-1.28 (6.03)	-2.57 (5.60)	-1.81 (6.73)	-1.76 (5.13)
DBP, Day 1, 4 hour	-1.86 (7.88)	-0.77 (6.56)	-2.00 (6.46)	-0.90 (6.81)	-1.69 (5.05)
DBP, Day 1, 8 hour	-2.16 (6.91)	-0.56 (6.42)	-0.73 (6.23)	-1.98 (6.23)	-1.52 (6.69)
DBP, Day 1, 12 hour	-1.40 (8.76)	-0.16 (7.16)	-1.64 (7.81)	-1.24 (6.14)	-0.38 (5.78)
DBP, Day 1, 24 hour	-1.14 (6.07)	-0.14 (6.24)	-1.14 (6.91)	-0.76 (6.84)	-2.38 (6.05)
DBP, Day 2, pre-dose	-1.24 (6.23)	-0.28 (6.08)	-1.02 (6.93)	-0.90 (7.16)	-2.33 (6.43)
DBP, Day 2, 5 minutes	-1.62 (7.05)	-0.81 (5.67)	-0.68 (6.46)	-0.88 (7.27)	-2.62 (5.79)
DBP, Day 2, 30 minutes	-1.71 (6.37)	-0.45 (6.74)	-1.79 (6.99)	-1.80 (6.99)	-2.45 (5.60)
DBP, Day 2, 1 hour	-1.65 (7.20)	-0.18 (6.95)	-1.68 (6.87)	-1.10 (6.84)	-1.80 (6.51)
DBP, Day 8, pre-dose	-1.50 (8.09)	-1.30 (6.65)	-0.88 (7.49)	0.02 (6.80)	-2.05 (6.18)
DBP, Day 8, 5 minutes	-2.45 (9.16)	-1.65 (6.94)	-0.98 (7.06)	-0.24 (5.72)	-2.38 (4.86)
DBP, Day 8, 30 minutes	-2.36 (7.19)	-1.93 (6.43)	-1.71 (7.10)	-0.70 (5.89)	-2.58 (4.68)
DBP, Day 8, 1 hour	-2.03 (7.15)	-0.93 (6.54)	-1.61 (7.42)	-1.63 (6.95)	-2.16 (5.54)
DBP, Day 15, pre-dose	-2.30 (8.17)	-0.10 (7.49)	-1.21 (6.46)	-0.90 (6.81)	-0.63 (6.74)
DBP, Day 15, 5 minutes	-2.70 (8.54)	-0.60 (8.26)	-0.98 (8.15)	-1.85 (6.57)	-1.33 (7.03)
DBP, Day 15, 30 minutes	-3.33 (7.98)	-0.05 (7.15)	-2.15 (7.73)	-2.39 (8.22)	-2.37 (6.26)
DBP, Day 15, 1 hour	-3.26 (5.95)	0.92 (7.57)	-2.23 (7.04)	-2.07 (7.31)	-2.24 (5.51)
DBP, Day 22, pre-dose	-1.21 (6.90)	-1.90 (6.53)	-0.67 (6.63)	0.63 (8.86)	-0.44 (8.08)
DBP, Day 22, 5 minutes	-3.05 (8.91)	-1.62 (6.27)	-1.67 (8.62)	-0.90 (8.44)	-2.54 (7.70)
DBP, Day 22, 30 minutes	-2.51 (7.91)	-2.53 (6.60)	-1.51 (7.44)	-0.98 (8.78)	-1.30 (6.45)
DBP, Day 22, 1 hour	-2.89 (6.88)	-1.36 (6.41)	-1.31 (7.16)	-1.35 (8.05)	-2.89 (6.67)
DBP, Day 27	-2.86 (7.04)	-1.00 (7.53)	-1.43 (6.32)	-0.75 (6.53)	-2.69 (6.22)
DBP, Day 28, pre-dose	-3.67 (6.62)	0.14 (5.71)	-1.31 (6.66)	0.25 (8.23)	-1.28 (6.30)
DBP, Day 28, 15 minutes	-4.37 (7.42)	-1.24 (9.26)	-1.19 (5.58)	-0.63 (8.20)	-1.28 (6.84)
DBP, Day 28, 30 minutes	-4.37 (7.25)	-0.81 (7.23)	-1.57 (6.01)	-1.05 (8.90)	-2.41 (6.83)
DBP, Day 28, 1 hour	-3.58 (7.11)	-2.00 (6.94)	-1.07 (7.63)	-1.45 (7.37)	-3.62 (5.98)
DBP, Day 28, 2 hour	-4.14 (8.05)	-2.41 (5.89)	-0.93 (6.69)	-2.13 (7.57)	-2.62 (5.42)
DBP, Day 28, 3 hour	-3.31 (7.58)	-2.70 (7.08)	-2.71 (5.26)	-2.15 (7.83)	-1.90 (6.18)
DBP, Day 28, 4 hour	-3.30 (7.23)	-1.57 (5.51)	-2.64 (5.92)	-2.10 (7.73)	-2.23 (5.44)
DBP, Day 28, 8 hour	-3.02 (7.16)	-1.03 (5.91)	-1.57 (6.91)	-1.10 (7.73)	-1.33 (6.32)
DBP, Day 28, 12 hour	-3.58 (6.27)	-1.82 (6.56)	-1.93 (5.85)	-0.90 (8.45)	-0.97 (6.97)
DBP, Day 28, 24 hour	-3.40 (8.66)	-0.71 (7.23)	-2.38 (5.41)	-1.35 (8.34)	-2.21 (6.83)
DBP, Day 35	-2.07 (9.11)	-0.69 (6.38)	-2.33 (8.06)	0.61 (7.29)	-1.46 (7.02)

5. Primary Outcome

Title	Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Description	Vital sign assessment of HR was done at Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose), Day 2 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 8 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 15 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 22 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 27, Day 28 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose) and Day 35. A window of plus or minus 5 minutes was allowed during the active treatment visit vital sign assessments. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1, Day 2, Day 8, Day 15, Day 22, Day 27, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1, pre-dose) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 1, 15 minutes	-0.02 (5.82)	1.02 (5.24)	0.23 (5.08)	1.21 (6.32)	1.60 (4.47)
Day 1, 30 minutes	0.05 (5.99)	1.12 (5.55)	0.47 (6.10)	1.12 (6.06)	0.26 (5.40)
Day 1, 1 hour	0.21 (6.16)	0.33 (5.84)	-0.35 (6.27)	-0.48 (7.19)	0.43 (4.88)
Day 1, 2 hour	-0.23 (5.63)	0.09 (5.95)	-1.16 (5.63)	-1.19 (5.56)	0.45 (5.55)
Day 1, 3 hour	-0.12 (5.39)	0.07 (6.25)	-1.19 (6.50)	0.12 (6.83)	0.19 (5.71)
Day 1, 4 hour	-1.37 (5.94)	-0.53 (6.04)	-0.40 (6.81)	-1.81 (5.64)	0.05 (6.03)
Day 1, 8 hour	-0.70 (6.00)	-0.79 (4.29)	-0.72 (5.15)	-2.14 (5.26)	0.95 (5.71)
Day 1, 12 hour	-1.05 (6.35)	-1.05 (4.77)	-0.72 (6.03)	-1.38 (5.58)	0.45 (6.66)
Day 1, 24 hour	0.12 (5.49)	-0.40 (5.57)	0.14 (5.09)	-0.19 (5.06)	0.64 (5.78)
Day 2, pre-dose	0.14 (6.11)	0.30 (6.06)	0.14 (5.02)	-0.14 (4.95)	0.81 (5.61)
Day 2, 5 minutes	1.33 (5.59)	1.00 (5.81)	-0.12 (5.69)	0.67 (5.85)	1.14 (5.34)
Day 2, 30 minutes	0.47 (4.97)	0.28 (5.80)	-0.08 (6.07)	-0.76 (5.61)	1.03 (4.70)
Day 2, 1 hour	-0.38 (4.50)	0.18 (5.85)	-1.13 (6.63)	-1.29 (6.30)	1.35 (4.92)
Day 8, pre-dose	0.79 (5.72)	-0.84 (6.74)	1.53 (8.69)	0.15 (7.80)	1.36 (6.47)
Day 8, 5 minutes	0.67 (5.15)	-0.56 (6.47)	1.12 (8.94)	-0.07 (8.13)	1.85 (6.31)
Day 8, 30 minutes	0.59 (5.92)	-0.15 (6.78)	-1.11 (7.51)	0.30 (8.46)	1.66 (5.56)
Day 8, 1 hour	0.47 (4.99)	-0.35 (6.91)	-1.26 (6.73)	-0.93 (7.45)	1.71 (6.23)
Day 15, pre-dose	-0.35 (7.53)	-0.53 (8.05)	0.23 (6.79)	-1.10 (8.42)	-0.43 (6.07)
Day 15, 5 minutes	-0.05 (6.69)	-0.55 (8.34)	0.43 (8.14)	-1.17 (8.44)	0.68 (6.36)
Day 15, 30 minutes	-0.72 (6.01)	-0.24 (8.31)	-0.49 (8.42)	-1.68 (8.30)	0.82 (6.08)
Day 15, 1 hour	-0.16 (5.25)	-0.81 (7.50)	-1.46 (7.08)	-0.73 (8.33)	0.13 (5.74)
Day 22, pre-dose	0.44 (7.10)	-1.33 (8.21)	1.33 (7.89)	-0.50 (10.19)	1.13 (7.45)
Day 22, 5 minutes	0.88 (6.90)	-0.59 (7.27)	0.88 (8.50)	-0.10 (9.16)	0.62 (6.74)
Day 22, 30 minutes	0.41 (7.02)	-1.08 (7.69)	0.05 (8.33)	0.53 (9.53)	0.51 (6.42)
Day 22, 1 hour	-0.21 (6.05)	-1.03 (8.11)	0.46 (7.45)	0.28 (9.25)	0.03 (7.02)
Day 27	-1.70 (6.94)	-1.19 (8.27)	-1.83 (6.58)	-0.75 (8.05)	-0.10 (5.91)
Day 28, pre-dose	-1.67 (6.92)	-1.95 (6.99)	-1.26 (5.44)	-0.73 (9.60)	-0.67 (5.89)
Day 28, 15 minutes	-0.67 (7.61)	-1.11 (7.44)	-0.50 (6.95)	-0.03 (10.28)	0.31 (5.66)
Day 28, 30 minutes	-0.60 (6.97)	-1.84 (6.99)	-0.12 (7.30)	-0.43 (9.47)	0.26 (5.73)
Day 28, 1 hour	-0.44 (6.55)	-1.76 (7.03)	-1.20 (6.75)	-1.18 (9.58)	0.69 (6.55)
Day 28, 2 hour	-1.40 (6.93)	-3.16 (6.13)	-1.20 (6.55)	-0.65 (9.23)	0.21 (6.88)
Day 28, 3 hour	-0.55 (6.56)	-1.97 (6.72)	-1.46 (7.41)	-1.53 (8.71)	0.36 (7.15)
Day 28, 4 hour	-0.91 (7.33)	-2.22 (6.94)	-1.24 (6.40)	-1.93 (9.45)	0.67 (7.19)
Day 28, 8 hour	-0.40 (7.47)	-2.14 (6.29)	-1.10 (6.87)	-1.63 (7.88)	0.05 (7.42)
Day 28, 12 hour	-1.72 (7.00)	-2.05 (6.15)	-2.02 (7.82)	-0.20 (8.29)	0.54 (7.57)
Day 28, 24 hour	-1.58 (7.43)	-1.50 (7.26)	-0.60 (5.49)	-1.33 (7.91)	-0.92 (6.59)
Day 35	-0.30 (7.20)	-1.90 (6.80)	-0.56 (6.62)	-3.15 (8.33)	0.56 (5.96)

6. Primary Outcome

Title	Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Description	Vital sign assessment of RR was done at Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose), Day 2 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 8 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 15 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 22 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 27, Day 28 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose) and Day 35. A window of plus or minus 5 minutes was allowed during the active treatment visit vital sign assessments. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1, Day 2, Day 8, Day 15, Day 22, Day 27, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1, pre-dose) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 1, 15 minutes	0.14 (0.89)	-0.07 (1.12)	-0.16 (1.15)	0.33 (0.79)	0.00 (0.99)
Day 1, 30 minutes	0.07 (1.10)	0.05 (1.11)	0.19 (0.96)	0.96 (1.11)	-0.02 (1.14)
Day 1, 1 hour	0.09 (0.97)	-0.12 (0.96)	-0.23 (1.09)	0.10 (1.08)	0.07 (0.97)
Day 1, 2 hour	-0.26 (0.93)	0.19 (1.14)	-0.37 (1.11)	0.10 (1.05)	0.21 (1.07)
Day 1, 3 hour	-0.02 (0.94)	0.02 (1.01)	-0.42 (1.10)	0.31 (1.09)	0.17 (1.26)
Day 1, 4 hour	-0.05 (1.09)	-0.07 (1.01)	-0.12 (1.12)	-0.02 (1.18)	0.07 (1.11)
Day 1, 8 hour	0.02 (1.20)	-0.02 (0.99)	-0.26 (1.27)	0.19 (1.09)	0.07 (0.89)
Day 1, 12 hour	-0.14 (1.06)	-0.05 (0.97)	-0.16 (0.92)	0.24 (1.05)	0.31 (1.07)
Day 1, 24 hour	-0.16 (1.00)	0.09 (1.25)	-0.45 (0.90)	-0.05 (0.76)	0.00 (0.83)
Day 2, pre-dose	0.00 (0.99)	0.09 (1.17)	-0.40 (0.90)	-0.02 (0.78)	0.00 (0.83)
Day 2, 5 minutes	0.29 (0.89)	0.02 (0.94)	-0.32 (1.01)	0.10 (1.01)	-0.02 (0.92)
Day 2, 30 minutes	0.18 (1.01)	0.10 (1.10)	-0.21 (0.93)	-0.15 (1.22)	-0.05 (1.06)
Day 2, 1 hour	0.11 (0.97)	0.13 (1.09)	-0.39 (0.97)	0.00 (0.74)	0.10 (0.90)
Day 8, pre-dose	0.02 (1.33)	0.00 (1.00)	-0.37 (1.18)	0.24 (0.99)	-0.21 (0.95)
Day 8, 5 minutes	-0.05 (1.08)	0.09 (1.00)	-0.43 (1.43)	0.24 (1.11)	-0.08 (1.07)
Day 8, 30 minutes	0.03 (1.04)	0.05 (1.32)	-0.50 (1.25)	0.35 (1.00)	-0.08 (0.97)
Day 8, 1 hour	0.05 (1.11)	0.00 (1.06)	-0.37 (1.15)	0.08 (1.10)	0.11 (0.98)
Day 15, pre-dose	0.09 (1.15)	-0.05 (1.06)	-0.58 (1.12)	0.17 (1.09)	0.00 (0.99)
Day 15, 5 minutes	-0.02 (1.24)	-0.15 (1.33)	-0.45 (1.37)	0.07 (1.10)	-0.08 (1.12)
Day 15, 30 minutes	0.05 (1.15)	-0.08 (1.02)	-0.28 (1.30)	0.17 (1.32)	0.03 (1.03)
Day 15, 1 hour	0.16 (1.08)	0.00 (1.37)	-0.64 (1.18)	0.10 (1.07)	-0.11 (1.01)
Day 22, pre-dose	-0.02 (1.22)	-0.05 (1.05)	-0.51 (1.18)	0.10 (1.10)	0.13 (1.03)
Day 22, 5 minutes	0.07 (1.10)	0.08 (1.20)	-0.62 (1.45)	0.25 (1.19)	0.13 (1.00)
Day 22, 30 minutes	0.10 (1.25)	-0.14 (1.29)	-0.51 (1.00)	0.20 (1.16)	0.03 (1.07)
Day 22, 1 hour	0.13 (1.19)	0.11 (1.09)	-0.41 (1.04)	0.38 (1.17)	0.00 (1.25)
Day 27	-0.14 (1.06)	0.11 (0.97)	-0.67 (1.14)	0.00 (1.28)	0.26 (1.16)
Day 28, pre-dose	-0.09 (1.17)	0.19 (1.05)	-0.71 (1.20)	0.10 (1.26)	0.03 (0.78)
Day 28, 15 minutes	-0.33 (1.23)	-0.08 (1.06)	-0.56 (1.12)	0.30 (1.36)	-0.05 (1.02)
Day 28, 30 minutes	-0.21 (1.06)	0.08 (1.23)	-0.32 (1.19)	0.10 (1.52)	-0.03 (1.04)
Day 28, 1 hour	-0.19 (1.30)	-0.08 (1.16)	-0.37 (0.99)	0.23 (1.54)	-0.05 (1.23)
Day 28, 2 hour	-0.33 (1.19)	-0.24 (1.04)	-0.68 (1.21)	0.30 (1.40)	-0.10 (0.97)
Day 28, 3 hour	-0.07 (1.30)	0.00 (1.31)	-0.56 (1.16)	0.10 (1.37)	-0.13 (1.08)
Day 28, 4 hour	-0.05 (1.27)	0.05 (1.08)	-0.46 (1.14)	0.25 (1.53)	0.05 (1.36)
Day 28, 8 hour	-0.33 (1.43)	0.14 (1.00)	-0.54 (0.98)	0.23 (1.29)	-0.08 (1.18)
Day 28, 12 hour	-0.35 (1.34)	0.05 (1.18)	-0.49 (1.14)	0.20 (1.11)	0.03 (1.25)
Day 28, 24 hour	-0.19 (1.19)	-0.03 (0.91)	-0.64 (1.10)	0.13 (1.45)	-0.18 (1.02)
Day 35	-0.35 (1.34)	0.05 (1.01)	-0.56 (1.10)	0.07 (1.47)	0.02 (0.88)

7. Primary Outcome

Title	Change From Baseline in Vital Sign Parameter of Temperature Over Time
Description	Vital sign assessment of temperature was done at Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose), Day 2 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 8 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 15 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 22 (pre-dose, 5 minutes, 30 minutes and 1 hour post-dose), Day 27, Day 28 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours and 24 hours post-dose) and Day 35. A window of plus or minus 5 minutes was allowed during the active treatment visit vital sign assessments. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1, Day 2, Day 8, Day 15, Day 22, Day 27, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1, pre-dose) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 1, 15 minutes	0.03 (0.12)	-0.00 (0.14)	0.01 (0.11)	0.04 (0.13)	0.01 (0.26)
Day 1, 30 minutes	0.04 (0.21)	-0.01 (0.12)	-0.00 (0.13)	0.04 (0.12)	0.03 (0.20)
Day 1, 1 hour	0.05 (0.18)	-0.00 (0.16)	0.00 (0.13)	0.04 (0.10)	0.03 (0.26)
Day 1, 2 hour	0.02 (0.19)	0.01 (0.20)	0.02 (0.14)	0.06 (0.15)	0.05 (0.21)
Day 1, 3 hour	0.05 (0.20)	-0.00 (0.18)	-0.03 (0.14)	0.06 (0.16)	0.01 (0.20)
Day 1, 4 hour	0.05 (0.17)	0.02 (0.18)	0.02 (0.18)	0.05 (0.15)	0.03 (0.26)
Day 1, 8 hour	0.07 (0.23)	0.03 (0.20)	0.03 (0.14)	0.05 (0.14)	0.02 (0.20)
Day 1, 12 hour	0.12 (0.24)	0.01 (0.17)	0.03 (0.18)	0.05 (0.15)	0.06 (0.23)
Day 1, 24 hour	0.03 (0.16)	-0.03 (0.23)	0.01 (0.18)	0.01 (0.19)	0.00 (0.23)
Day 2, pre-dose	0.02 (0.15)	-0.03 (0.23)	0.02 (0.18)	0.01 (0.19)	0.01 (0.23)
Day 2, 5 minutes	0.02 (0.18)	-0.00 (0.18)	0.01 (0.16)	-0.03 (0.16)	0.05 (0.21)
Day 2, 30 minutes	0.05 (0.13)	-0.00 (0.15)	-0.01 (0.14)	0.02 (0.17)	0.06 (0.22)
Day 2, 1 hour	0.04 (0.11)	-0.00 (0.16)	-0.00 (0.16)	0.03 (0.14)	0.04 (0.23)
Day 8, pre-dose	0.07 (0.25)	0.03 (0.17)	0.00 (0.24)	0.02 (0.18)	-0.01 (0.22)
Day 8, 5 minutes	0.05 (0.21)	0.03 (0.18)	0.01 (0.19)	0.01 (0.17)	0.03 (0.21)
Day 8, 30 minutes	0.06 (0.20)	0.00 (0.16)	-0.03 (0.19)	0.03 (0.17)	0.04 (0.20)
Day 8, 1 hour	0.03 (0.14)	0.01 (0.16)	-0.02 (0.21)	0.03 (0.20)	0.03 (0.24)
Day 15, pre-dose	0.03 (0.24)	0.00 (0.17)	0.02 (0.19)	0.06 (0.21)	0.01 (0.19)
Day 15, 5 minutes	0.05 (0.20)	0.01 (0.18)	0.01 (0.20)	0.05 (0.17)	0.02 (0.24)
Day 15, 30 minutes	0.07 (0.20)	-0.01 (0.20)	-0.01 (0.18)	0.05 (0.18)	0.03 (0.21)
Day 15, 1 hour	0.05 (0.14)	0.04 (0.15)	-0.02 (0.19)	0.04 (0.15)	0.01 (0.15)
Day 22, pre-dose	0.00 (0.20)	0.04 (0.25)	-0.02 (0.13)	-0.01 (0.25)	0.01 (0.10)
Day 22, 5 minutes	0.01 (0.17)	0.04 (0.23)	-0.00 (0.16)	-0.01 (0.20)	0.00 (0.12)
Day 22, 30 minutes	0.04 (0.16)	0.04 (0.21)	-0.03 (0.12)	0.03 (0.23)	0.01 (0.10)
Day 22, 1 hour	0.02 (0.17)	0.05 (0.21)	0.01 (0.14)	0.02 (0.22)	0.01 (0.09)
Day 27	0.04 (0.21)	0.01 (0.24)	0.01 (0.20)	0.05 (0.21)	0.03 (0.13)
Day 28, pre-dose	-0.00 (0.17)	-0.00 (0.18)	-0.01 (0.19)	0.00 (0.19)	-0.01 (0.18)
Day 28, 15 minutes	0.02 (0.17)	-0.00 (0.20)	0.00 (0.18)	0.04 (0.21)	-0.00 (0.17)
Day 28, 30 minutes	0.02 (0.15)	-0.01 (0.24)	-0.01 (0.17)	0.05 (0.24)	0.02 (0.17)
Day 28, 1 hour	0.02 (0.17)	-0.04 (0.28)	-0.01 (0.15)	0.04 (0.24)	0.00 (0.12)
Day 28, 2 hour	0.03 (0.19)	-0.00 (0.25)	-0.04 (0.16)	0.04 (0.18)	0.02 (0.13)
Day 28, 3 hour	0.02 (0.13)	0.01 (0.26)	-0.01 (0.21)	0.02 (0.22)	0.00 (0.16)
Day 28, 4 hour	-0.01 (0.25)	0.00 (0.27)	-0.02 (0.16)	0.02 (0.22)	0.01 (0.11)
Day 28, 8 hour	0.05 (0.21)	0.05 (0.24)	0.00 (0.17)	0.05 (0.17)	0.02 (0.16)
Day 28, 12 hour	0.05 (0.16)	0.06 (0.27)	0.01 (0.18)	0.05 (0.21)	-0.01 (0.15)
Day 28, 24 hour	-0.01 (0.22)	-0.02 (0.25)	-0.09 (0.35)	0.02 (0.26)	-0.02 (0.19)
Day 35	-0.00 (0.24)	0.07 (0.18)	-0.02 (0.18)	0.07 (0.23)	0.02 (0.32)

8. Primary Outcome

Title	Change From Baseline in Electrocardiogram (ECG) Values Over Time
Description	12-lead ECG was obtained in the rested state. Participants lied in supine position with ECG leads on for at least 5 minutes prior to ECG recording. The ECG was performed at Day 1 (pre-dose and post-dose), Day 8, Day 15, Day 22, Day 28 (pre-dose and pre-dose) and Day 35, and included the assessment of PR interval, QRS interval, QT interval and QTc interval. Baseline was defined as the assessment done on Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline value (Day 1, pre-dose) from the individual post-Baseline (Day 1 [post-dose], Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1, pre-dose) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
PR interval, Day 1, post-dose	0.12 (9.92)	1.47 (13.07)	0.58 (12.43)	0.32 (9.96)	1.57 (11.91)
PR interval, Day 8	-0.26 (17.29)	-3.42 (18.04)	0.45 (14.15)	-2.46 (14.66)	-3.63 (15.56)
PR interval, Day 15	-5.79 (15.29)	-3.20 (16.45)	-5.10 (19.64)	-0.78 (12.10)	-1.03 (12.96)
PR interval, Day 22	-2.38 (16.84)	-0.31 (18.12)	-1.19 (14.86)	0.15 (12.31)	-1.46 (14.71)
PR interval, Day 28, pre-dose	-0.55 (14.81)	-3.46 (18.59)	-2.39 (14.43)	3.70 (13.45)	0.31 (17.74)
PR interval, Day 28, post-dose	-1.98 (15.72)	-1.22 (17.40)	-1.59 (16.55)	1.88 (15.35)	3.33 (13.27)
PR interval, Day 35	-0.07 (16.43)	-1.22 (25.54)	0.48 (19.88)	1.95 (13.81)	1.15 (10.41)
QRS interval, Day 1, post-dose	-0.83 (8.31)	1.07 (9.67)	-0.16 (3.31)	0.54 (7.18)	1.45 (8.12)
QRS interval, Day 8	-0.50 (7.74)	-17.49 (107.04)	0.81 (6.78)	0.56 (7.23)	0.85 (10.15)
QRS interval, Day 15	-1.05 (6.89)	-16.15 (110.73)	-0.17 (6.26)	-1.37 (11.87)	0.80 (8.16)
QRS interval, Day 22	0.14 (5.88)	-19.31 (112.93)	-0.26 (7.15)	-1.00 (5.43)	0.28 (9.51)
QRS interval, Day 28, pre-dose	-0.81 (9.55)	-20.00 (120.11)	-0.54 (6.24)	-1.28 (6.80)	-0.54 (7.41)
QRS interval, Day 28, post-dose	-0.14 (11.71)	-19.38 (120.28)	-0.85 (7.62)	-0.03 (6.62)	0.21 (9.09)
QRS interval, Day 35	-0.36 (6.55)	-12.39 (112.59)	-1.21 (5.58)	-1.17 (10.59)	0.83 (8.89)
QT interval, Day 1, post-dose	-0.29 (14.09)	-2.44 (20.72)	1.23 (18.96)	3.49 (18.44)	1.17 (17.14)
QT interval, Day 8	-1.17 (18.65)	-7.56 (32.44)	-2.74 (21.35)	0.68 (13.49)	-2.98 (25.80)
QT interval, Day 15	0.93 (23.43)	0.40 (21.66)	-0.66 (22.63)	-0.98 (15.75)	1.53 (19.98)
QT interval, Day 22	1.38 (20.93)	1.31 (21.31)	1.36 (22.41)	-6.00 (18.92)	0.64 (18.54)
QT interval, Day 28, pre-dose	9.17 (25.76)	1.62 (19.05)	1.46 (27.63)	3.48 (20.88)	1.00 (18.20)
QT interval, Day 28, post-dose	0.90 (34.52)	4.27 (18.31)	3.80 (24.89)	4.35 (24.70)	-1.28 (24.60)
QT interval, Day 35	2.10 (22.76)	4.56 (22.44)	0.36 (20.27)	5.12 (26.01)	4.27 (27.43)
QTc interval, Day 1, post-dose	-2.52 (16.05)	-1.60 (16.31)	1.28 (14.46)	3.37 (18.91)	-1.71 (23.06)
QTc interval, Day 8	5.02 (21.98)	-3.40 (27.38)	3.64 (20.77)	4.17 (20.65)	1.45 (25.90)
QTc interval, Day 15	-0.57 (21.03)	-3.05 (26.25)	2.78 (15.96)	0.68 (19.64)	4.40 (23.37)
QTc interval, Day 22	3.21 (17.87)	-4.21 (17.59)	5.52 (17.55)	-4.13 (23.18)	-0.10 (22.32)
QTc interval, Day 28, pre-dose	4.98 (17.02)	2.35 (18.90)	-0.71 (24.18)	1.50 (19.86)	-4.67 (19.30)
QTc interval, Day 28, post-dose	2.05 (21.32)	0.54 (21.20)	2.39 (23.09)	0.83 (19.86)	-4.44 (20.43)
QTc interval, Day 35	2.38 (19.88)	-0.05 (21.78)	2.90 (16.15)	0.63 (26.55)	-1.34 (28.57)

9. Primary Outcome

Title	Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Description	Assessment for basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and white blood cell (WBC) count were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Baseophil count, Day 8	0.01 (0.02)	0.00 (0.02)	0.00 (0.01)	0.00 (0.02)	-0.00 (0.02)
Baseophil count, Day 15	0.01 (0.02)	0.01 (0.03)	0.01 (0.03)	-0.00 (0.02)	-0.00 (0.02)
Baseophil count, Day 22	0.01 (0.01)	0.01 (0.03)	-0.00 (0.02)	-0.00 (0.02)	-0.01 (0.02)
Baseophil count, Day 28	0.01 (0.02)	0.00 (0.02)	0.00 (0.02)	-0.00 (0.02)	-0.00 (0.02)
Baseophil count Day 35	0.00 (0.02)	0.01 (0.02)	0.00 (0.02)	0.00 (0.02)	-0.00 (0.02)
Eosinophil count, Day 8	0.01 (0.14)	0.01 (0.13)	0.03 (0.17)	-0.01 (0.09)	0.01 (0.14)
Eosinophil count, Day 15	-0.04 (0.13)	0.01 (0.12)	0.04 (0.28)	0.01 (0.11)	-0.03 (0.12)
Eosinophil count, Day 22	-0.01 (0.21)	0.01 (0.10)	0.01 (0.15)	0.02 (0.20)	0.03 (0.16)
Eosinophil count, Day 28	-0.05 (0.11)	0.02 (0.13)	0.02 (0.27)	-0.00 (0.10)	0.02 (0.17)
Eosinophil count, Day 35	-0.02 (0.15)	-0.01 (0.14)	0.03 (0.24)	-0.02 (0.11)	0.05 (0.21)
Lymphocyte count, Day 8	0.12 (0.44)	0.20 (0.59)	0.10 (0.46)	0.12 (0.53)	0.20 (0.58)
Lymphocyte count, Day 15	0.22 (0.52)	0.10 (0.58)	0.16 (0.41)	0.11 (0.46)	0.05 (0.46)
Lymphocyte count, Day 22	0.14 (0.46)	0.17 (0.54)	0.22 (0.43)	-0.00 (0.43)	0.04 (0.36)
Lymphocyte count, Day 28	0.05 (0.48)	-0.03 (0.49)	0.49 (0.47)	-0.02 (0.47)	-0.07 (0.47)
Lymphocyte count, Day 35	0.16 (0.45)	0.15 (0.58)	0.18 (0.43)	0.06 (0.46)	0.10 (0.57)
Monocyte count, Day 8	0.04 (0.11)	0.02 (0.16)	0.03 (0.13)	0.04 (0.15)	0.05 (0.18)
Monocyte count, Day 15	0.02 (0.12)	0.02 (0.18)	0.04 (0.12)	0.04 (0.14)	0.04 (0.15)
Monocyte count, Day 22	0.05 (0.13)	0.05 (0.19)	0.01 (0.13)	0.00 (0.18)	0.05 (0.16)
Monocyte count, Day 28	0.00 (0.11)	-0.03 (0.15)	-0.00 (0.13)	-0.01 (0.11)	0.00 (0.17)
Monocyte count, Day 35	0.03 (0.11)	0.02 (0.15)	0.00 (0.15)	-0.01 (0.15)	0.02 (0.16)
Neutrophil count, Day 8	0.01 (1.08)	0.37 (1.29)	0.11 (1.05)	0.10 (1.23)	0.03 (1.11)
Neutrophil count, Day 15	0.15 (0.83)	0.55 (1.19)	0.27 (0.88)	0.31 (1.27)	0.46 (1.40)
Neutrophil count, Day 22	-0.07 (0.82)	0.56 (1.31)	0.31 (0.71)	0.14 (1.38)	0.20 (1.59)
Neutrophil count, Day 28	0.08 (1.34)	0.35 (1.23)	-0.18 (0.96)	0.19 (1.21)	0.26 (1.28)
Neutrophil count, Day 35	0.05 (1.27)	0.29 (1.18)	0.09 (0.63)	0.28 (1.13)	0.55 (1.40)
Platelet count, Day 8	6.37 (35.76)	4.03 (40.19)	2.34 (26.94)	12.14 (28.82)	5.75 (23.95)
Platelet count, Day 15	15.19 (41.90)	13.45 (39.23)	13.10 (28.86)	15.40 (30.99)	7.73 (28.91)
Platelet count, Day 22	9.28 (33.79)	9.49 (42.29)	16.42 (27.73)	19.70 (29.51)	4.49 (30.38)
Platelet count, Day 28	-3.05 (33.65)	3.81 (45.00)	7.11 (21.05)	5.22 (34.65)	8.73 (43.33)
Platelet count, Day 35	10.89 (31.69)	6.27 (42.88)	11.58 (26.85)	20.65 (35.89)	15.75 (37.58)
WBC count, Day 8	0.15 (1.36)	0.43 (1.66)	0.37 (1.27)	0.09 (1.45)	0.22 (1.49)
WBC count, Day 15	0.35 (0.94)	0.67 (1.36)	0.59 (1.10)	0.44 (1.33)	0.49 (1.60)
WBC count, Day 22	0.15 (0.92)	0.75 (1.64)	0.58 (0.94)	0.18 (1.62)	0.31 (1.76)
WBC count, Day 28	0.12 (1.43)	0.21 (1.56)	0.03 (1.20)	0.02 (1.41)	0.20 (1.46)
WBC count, Day 35	0.23 (1.29)	0.29 (1.53)	0.34 (0.90)	0.26 (1.21)	0.66 (1.68)

10. Primary Outcome

Title	Change From Baseline in Hematology Parameter of Red Blood Cell (RBC) Count Over Time
Description	Assessment for RBC count was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 8	-0.02 (0.19)	0.03 (0.31)	-0.02 (0.24)	0.03 (0.23)	0.03 (0.20)
Day 15	0.01 (0.19)	0.02 (0.39)	-0.04 (0.22)	-0.03 (0.21)	0.02 (0.24)
Day 22	0.04 (0.48)	0.03 (0.36)	-0.04 (0.22)	-0.01 (0.27)	-0.01 (0.20)
Day 28	-0.02 (0.25)	-0.10 (0.38)	-0.11 (0.23)	-0.09 (0.33)	-0.12 (0.23)
Day 35	-0.08 (0.27)	-0.10 (0.35)	-0.14 (0.21)	-0.13 (0.41)	-0.12 (0.21)

11. Primary Outcome

Title	Change From Baseline in Hematology Parameter of Hematocrit Over Time
Description	Assessment for hematocrit was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 8	-0.00 (0.02)	0.00 (0.03)	-0.00 (0.03)	0.00 (0.03)	0.00 (0.02)
Day 15	0.00 (0.02)	0.00 (0.04)	-0.00 (0.02)	-0.00 (0.02)	-0.00 (0.02)
Day 22	0.01 (0.05)	0.01 (0.03)	-0.00 (0.02)	-0.00 (0.03)	-0.00 (0.02)
Day 28	-0.00 (0.02)	-0.01 (0.04)	-0.01 (0.02)	-0.01 (0.04)	-0.01 (0.03)
Day 35	-0.00 (0.03)	-0.01 (0.03)	-0.01 (0.02)	-0.01 (0.03)	-0.01 (0.02)

12. Primary Outcome

Title	Change From Baseline in Hematology Parameter of Hemoglobin Over Time
Description	Assessment for hemoglobin was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 8	-0.75 (5.17)	1.49 (9.28)	-0.03 (7.36)	0.47 (8.03)	1.44 (6.58)
Day 15	0.31 (5.13)	1.09 (11.65)	-0.32 (7.21)	-0.81 (8.25)	0.40 (6.70)
Day 22	-1.08 (5.87)	1.05 (10.71)	-0.57 (7.56)	-0.82 (9.70)	-0.05 (5.92)
Day 28	-0.43 (7.34)	-2.60 (11.34)	-2.32 (7.83)	-2.58 (10.49)	-3.83 (6.88)
Day 35	-2.19 (8.37)	-2.33 (11.10)	-3.50 (7.53)	-4.75 (9.87)	-3.08 (6.16)

13. Primary Outcome

Title	Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Over Time
Description	Assessment for mean corpuscular hemoglobin was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 8	0.00 (0.72)	0.15 (0.79)	0.23 (0.62)	-0.16 (0.82)	0.17 (0.67)
Day 15	0.03 (0.58)	0.23 (1.14)	0.27 (0.63)	-0.03 (0.81)	-0.08 (0.53)
Day 22	-0.24 (1.79)	0.14 (0.79)	0.14 (0.65)	-0.18 (0.90)	0.10 (0.64)
Day 28	0.10 (0.74)	0.11 (0.96)	0.39 (0.67)	0.03 (0.94)	0.00 (0.60)
Day 35	0.11 (0.82)	0.05 (1.36)	0.38 (0.66)	-0.11 (1.74)	0.08 (0.73)

14. Primary Outcome

Title	Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Concentration Over Time
Description	Assessment for mean corpuscular hemoglobin concentration was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 8	-1.43 (8.10)	0.00 (7.56)	0.77 (8.39)	0.56 (9.24)	3.33 (9.24)
Day 15	0.59 (7.36)	0.31 (8.22)	2.16 (7.50)	-0.63 (11.34)	0.31 (8.61)
Day 22	-4.00 (21.58)	-1.25 (8.33)	0.25 (9.47)	-2.29 (11.65)	1.56 (7.67)
Day 28	-1.56 (8.08)	1.85 (8.34)	1.47 (6.57)	-0.59 (12.78)	0.00 (8.77)
Day 35	-2.35 (7.81)	0.32 (11.69)	-0.81 (7.22)	0.32 (12.51)	-1.54 (7.32)

15. Primary Outcome

Title	Change From Baseline in Hematology Parameter of Mean Corpuscular Volume Over Time
Description	Assessment for mean corpuscular volume was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 8	0.20 (1.21)	0.28 (1.77)	0.18 (1.68)	-0.33 (2.24)	-0.17 (1.53)
Day 15	0.29 (1.29)	0.69 (3.35)	0.11 (1.54)	-0.06 (2.71)	-0.03 (1.45)
Day 22	0.17 (1.98)	0.59 (1.70)	0.05 (1.72)	0.03 (2.27)	0.13 (1.66)
Day 28	0.81 (1.89)	-0.19 (2.43)	0.29 (1.17)	0.29 (2.70)	0.22 (1.72)
Day 35	1.00 (1.74)	0.74 (3.01)	0.73 (1.63)	-0.71 (4.27)	0.77 (1.70)

16. Primary Outcome

Title	Change From Baseline in Coagulation Parameters of Activated Partial Thromplastin Time (aPTT) and Prothrombin Time (PT) Over Time
Description	Assessment for aPTT and PT were performed on Day 1, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28 and Day 35) values.
Time Frame	Baseline (Day 1), Day 28 and Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
aPTT, Day 28	0.53 (6.78)	1.51 (9.88)	-1.58 (6.98)	1.41 (13.03)	1.26 (10.07)
aPTT, Day 35	-0.43 (6.99)	-1.73 (4.28)	-1.46 (4.31)	-1.28 (4.33)	-0.84 (5.26)
PT, Day 28	-0.28 (1.62)	0.18 (2.68)	0.20 (2.99)	-0.18 (1.43)	-0.36 (1.99)
PT, Day 35	-0.49 (1.62)	-0.45 (1.13)	-0.26 (0.83)	-0.47 (2.07)	-0.44 (0.94)

17. Primary Outcome

Title	Change From Baseline in Coagulation Parameter of International Normalized Ratio Over Time
Description	Assessment for international normalized ratio was performed on Day 1, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28 and Day 35) values.
Time Frame	Baseline (Day 1), Day 28 and Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 28	-0.02 (0.13)	0.02 (0.24)	0.01 (0.24)	-0.01 (0.11)	-0.03 (0.16)
Day 35	-0.04 (0.13)	-0.03 (0.09)	-0.02 (0.07)	-0.04 (0.16)	-0.04 (0.07)

18. Primary Outcome

Title	Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
Description	Assessment for ALT, AST, ALP, creatinine phosphokinase and LDH were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
ALT, Day 8	0.90 (8.33)	-0.90 (6.99)	1.18 (10.46)	-1.53 (6.48)	-0.46 (8.49)
ALT, Day 15	1.03 (15.17)	-0.54 (7.99)	-0.21 (10.54)	-2.69 (6.69)	-1.95 (8.92)
ALT, Day 22	0.13 (13.64)	3.05 (13.37)	-0.41 (10.98)	-0.21 (9.78)	-3.71 (11.15)
ALT, Day 28	-2.79 (11.14)	0.56 (13.18)	-0.47 (13.17)	-2.27 (9.81)	-3.86 (11.10)
ALT, Day 35	-2.49 (11.86)	-0.38 (9.43)	-0.97 (10.85)	-3.06 (9.14)	-3.13 (11.78)
ALP, Day 8	-3.22 (7.60)	-0.63 (9.80)	-1.60 (8.15)	-3.24 (9.00)	0.63 (9.90)
ALP, Day 15	-1.61 (15.02)	-4.17 (14.55)	-2.05 (12.83)	-5.67 (18.08)	-1.65 (10.35)
ALP, Day 22	-3.17 (10.10)	-0.55 (17.35)	-0.22 (13.95)	-2.08 (19.56)	-2.20 (12.29)
ALP, Day 28	-4.73 (12.20)	-1.34 (19.89)	-3.33 (14.41)	-4.61 (18.06)	-4.05 (15.79)
ALP, Day 35	-5.95 (12.74)	-2.10 (15.76)	-2.71 (13.71)	-6.34 (16.37)	-4.69 (16.79)
AST, Day 8	-1.33 (10.28)	-1.25 (6.30)	-0.63 (6.92)	-1.18 (10.44)	0.46 (4.89)
AST, Day 15	-0.97 (13.71)	-0.54 (6.27)	-0.38 (9.60)	-2.85 (11.39)	0.37 (5.27)
AST, Day 22	-1.36 (11.82)	1.47 (6.43)	-0.95 (11.51)	-0.97 (12.87)	-1.50 (6.33)
AST, Day 28	-2.28 (11.28)	-1.39 (6.93)	-0.69 (9.92)	-2.23 (11.76)	-1.44 (4.95)
AST, Day 35	-2.14 (11.95)	-1.38 (6.52)	-0.82 (10.05)	-1.88 (12.15)	-1.88 (5.21)
Creatinine phosphokinase, Day 8	-4.05 (30.14)	11.25 (79.26)	-10.95 (84.04)	-3.11 (30.12)	-8.37 (100.00)
Creatinine phosphokinase, Day 15	-9.03 (39.62)	4.46 (33.64)	-10.23 (77.79)	-7.06 (43.44)	-0.05 (101.77)
Creatinine phosphokinase, Day 22	0.28 (33.55)	27.54 (97.86)	-19.40 (74.31)	6.47 (33.44)	-9.18 (100.75)
Creatinine phosphokinase, Day 28	-3.74 (51.30)	2.61 (32.25)	-15.03 (84.44)	12.65 (40.68)	-3.47 (110.21)
Creatinine phosphokinase, Day 35	-4.65 (23.19)	0.38 (31.87)	-12.58 (82.07)	8.30 (33.05)	-4.33 (104.54)
LDH, Day 8	-9.27 (55.02)	0.03 (20.69)	1.51 (20.44)	-5.23 (18.38)	-0.54 (14.93)
LDH, Day 15	-3.31 (52.15)	0.58 (20.51)	-2.45 (23.63)	-6.09 (29.60)	-2.64 (16.74)
LDH, Day 22	-8.84 (58.19)	-0.33 (21.26)	-2.34 (22.19)	-3.61 (22.03)	-3.42 (16.53)
LDH, Day 28	-11.27 (56.13)	-5.04 (19.71)	-7.44 (18.31)	-6.70 (16.99)	-1.48 (16.83)
LDH, Day 35	-7.47 (60.72)	-1.74 (20.90)	2.19 (25.99)	-1.65 (23.37)	-3.68 (16.18)

19. Primary Outcome

Title	Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Description	Assessment for bicarbonate, BUN, calcium, chloride, magnesium, phosphate, potassium and sodium were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Bicarbonate, Day 8	0.74 (2.69)	0.78 (3.01)	0.62 (2.40)	0.13 (2.48)	-0.17 (2.64)
Bicarbonate, Day 15	0.85 (2.36)	1.47 (2.68)	0.41 (2.45)	0.42 (2.52)	0.03 (2.86)
Bicarbonate, Day 22	0.65 (2.71)	1.45 (2.69)	0.90 (2.96)	0.03 (2.49)	0.00 (2.60)
Bicarbonate, Day 28	-0.09 (2.61)	0.40 (2.66)	-0.37 (2.67)	-0.13 (2.42)	-0.68 (1.97)
Bicarbonate, Day 35	0.68 (2.96)	0.51 (2.61)	0.60 (2.65)	-0.14 (2.31)	-0.48 (2.75)
BUN, Day 8	-0.09 (1.40)	0.30 (2.05)	0.29 (1.39)	0.15 (1.40)	0.03 (1.19)
BUN, Day 15	-0.06 (1.43)	0.16 (2.19)	0.15 (1.00)	0.42 (1.33)	0.36 (1.46)
BUN, Day 22	-0.03 (1.21)	0.36 (2.01)	0.27 (1.16)	0.01 (1.46)	0.16 (1.16)
BUN, Day 28	0.25 (1.39)	0.91 (2.11)	0.24 (1.29)	-0.15 (1.49)	0.09 (1.25)
BUN, Day 35	-0.07 (1.51)	0.35 (1.78)	0.22 (1.40)	-0.57 (1.37)	-0.11 (1.40)
Calcium, Day 8	0.03 (0.09)	0.02 (0.12)	0.03 (0.11)	0.05 (0.10)	0.02 (0.09)
Calcium, Day 15	0.04 (0.10)	0.00 (0.15)	0.01 (0.10)	0.05 (0.12)	-0.01 (0.10)
Calcium, Day 22	0.02 (0.08)	0.01 (0.13)	0.01 (0.10)	0.05 (0.08)	-0.00 (0.09)
Calcium, Day 28	0.00 (0.11)	-0.02 (0.15)	-0.03 (0.12)	0.02 (0.11)	-0.04 (0.10)
Calcium, Day 35	0.02 (0.11)	-0.01 (0.11)	-0.00 (0.09)	0.02 (0.08)	-0.02 (0.11)
Chloride, Day 8	0.45 (2.44)	-0.14 (3.07)	0.46 (2.96)	0.12 (2.82)	-0.80 (2.72)
Chloride, Day 15	0.24 (3.01)	0.00 (3.16)	0.29 (2.63)	0.90 (2.50)	-0.71 (3.39)
Chloride, Day 22	0.57 (2.61)	-0.26 (3.27)	0.45 (2.98)	1.10 (3.11)	-0.65 (3.00)
Chloride, Day 28	-0.17 (2.78)	0.17 (3.30)	0.54 (3.06)	0.43 (3.27)	0.00 (3.45)
Chloride, Day 35	0.49 (3.00)	0.98 (2.88)	1.40 (3.00)	1.38 (3.13)	0.95 (3.09)
Magnesium, Day 8	0.01 (0.07)	0.00 (0.06)	-0.02 (0.06)	-0.01 (0.06)	0.01 (0.06)
Magnesium, Day 15	0.01 (0.06)	-0.01 (0.07)	-0.01 (0.06)	-0.01 (0.06)	-0.00 (0.04)
Magnesium, Day 22	0.01 (0.08)	0.00 (0.07)	-0.01 (0.06)	0.00 (0.06)	-0.00 (0.08)
Magnesium, Day 28	0.00 (0.06)	-0.01 (0.06)	-0.02 (0.06)	0.01 (0.06)	-0.01 (0.05)
Magnesium, Day 35	-0.01 (0.06)	-0.02 (0.08)	-0.01 (0.06)	-0.00 (0.08)	-0.00 (0.07)
Phosphate, Day 8	-0.02 (0.21)	-0.02 (0.19)	-0.00 (0.18)	-0.03 (0.20)	0.03 (0.13)
Phosphate, Day 15	0.04 (0.21)	-0.01 (0.16)	-0.01 (0.15)	-0.04 (0.20)	-0.01 (0.17)
Phosphate, Day 22	0.01 (0.21)	0.04 (0.19)	-0.01 (0.16)	-0.03 (0.22)	-0.00 (0.18)
Phosphate, Day 28	-0.00 (0.20)	-0.00 (0.19)	0.02 (0.18)	-0.03 (0.22)	-0.00 (0.16)
Phosphate, Day 35	-0.00 (0.20)	-0.04 (0.18)	-0.01 (0.14)	-0.02 (0.23)	0.04 (0.21)
Potassium, Day 8	0.29 (0.48)	0.11 (0.38)	0.27 (0.45)	0.24 (0.47)	0.19 (0.42)
Potassium, Day 15	0.23 (0.46)	0.16 (0.35)	0.25 (0.41)	0.34 (0.47)	0.13 (0.35)
Potassium, Day 22	0.19 (0.53)	0.13 (0.40)	0.28 (0.41)	0.31 (0.51)	0.14 (0.40)
Potassium, Day 28	0.00 (0.43)	-0.02 (0.52)	0.07 (0.37)	0.03 (0.48)	-0.20 (0.31)
Potassium, Day 35	0.25 (0.59)	0.07 (0.45)	0.23 (0.35)	0.20 (0.44)	0.10 (0.42)
Sodium, Day 8	0.05 (2.48)	-0.33 (2.72)	0.29 (2.62)	0.05 (2.93)	-0.41 (2.74)
Sodium, Day 15	0.10 (3.08)	-0.53 (2.69)	-0.31 (2.57)	0.80 (2.90)	-0.59 (3.19)
Sodium, Day 22	0.31 (2.42)	-0.46 (2.34)	0.29 (2.80)	1.03 (3.06)	-0.63 (2.83)
Sodium, Day 28	0.07 (2.87)	-0.11 (3.35)	-0.15 (2.82)	0.73 (2.67)	-0.40 (3.09)
Sodium, Day 35	0.71 (2.94)	0.07 (2.78)	0.57 (3.01)	1.10 (2.33)	0.24 (2.41)

20. Primary Outcome

Title	Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Description	Assessment for direct bilirubin, indirect bilirubin, serum creatinine, total bilirubin and uric acid were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Direct bilirubin, Day 8	-0.05 (0.88)	0.26 (0.78)	0.27 (0.65)	0.13 (0.55)	0.30 (0.88)
Direct bilirubin, Day 15	0.11 (0.68)	0.19 (0.60)	0.13 (0.52)	-0.06 (0.44)	0.43 (0.90)
Direct bilirubin, Day 22	0.19 (0.70)	0.10 (0.70)	0.08 (0.35)	0.03 (0.74)	0.21 (0.58)
Direct bilirubin, Day 28	-0.08 (0.59)	0.07 (0.38)	0.19 (0.74)	-0.11 (0.50)	0.26 (0.85)
Direct bilirubin, Day 35	-0.06 (0.92)	-0.06 (0.60)	-0.05 (0.32)	-0.25 (0.67)	0.00 (0.53)
Indirect bilirubin, Day 8	-0.30 (3.02)	1.06 (3.31)	1.49 (3.52)	0.91 (3.32)	1.22 (4.36)
Indirect bilirubin, Day 15	0.31 (2.47)	0.71 (4.03)	0.56 (2.55)	0.52 (3.37)	1.22 (2.90)
Indirect bilirubin, Day 22	0.70 (3.44)	0.61 (3.04)	0.62 (3.27)	1.09 (3.37)	0.39 (2.69)
Indirect bilirubin, Day 28	-0.58 (3.59)	0.04 (3.21)	0.38 (2.69)	-0.36 (2.68)	-0.37 (3.53)
Indirect bilirubin, Day 35	-0.38 (3.37)	-0.38 (3.56)	-0.08 (2.95)	-1.63 (3.90)	-1.24 (2.78)
Serum creatinine, Day 8	0.31 (6.78)	1.68 (8.98)	4.27 (8.20)	5.26 (9.20)	7.15 (10.89)
Serum creatinine, Day 15	-1.05 (6.80)	1.00 (8.91)	2.21 (6.97)	2.45 (8.30)	5.83 (10.15)
Serum creatinine, Day 22	-0.74 (6.97)	1.13 (10.01)	2.57 (7.17)	2.61 (9.49)	5.50 (8.23)
Serum creatinine, Day 28	-1.12 (7.38)	1.09 (9.24)	1.85 (9.47)	1.03 (6.89)	2.78 (9.16)
Serum creatinine, Day 35	-0.75 (7.50)	0.07 (9.91)	0.93 (6.87)	-1.46 (6.89)	0.40 (8.00)
Total bilirubin, Day 8	-0.49 (3.72)	1.24 (3.73)	1.77 (4.13)	1.39 (3.78)	2.08 (6.16)
Total bilirubin, Day 15	0.44 (3.16)	1.25 (4.16)	0.73 (2.95)	1.68 (4.87)	1.95 (4.42)
Total bilirubin, Day 22	0.98 (3.75)	1.05 (3.38)	0.83 (3.41)	1.76 (3.97)	1.21 (4.57)
Total bilirubin, Day 28	-0.64 (4.17)	0.17 (3.46)	0.90 (3.39)	0.30 (4.22)	-0.03 (5.22)
Total bilirubin, Day 35	-0.62 (4.24)	-0.33 (3.72)	-0.32 (3.39)	-1.81 (5.34)	-1.39 (3.28)
Uric acid, Day 8	1.38 (38.94)	-8.66 (55.20)	-22.90 (48.36)	-20.95 (61.72)	-26.20 (66.02)
Uric acid, Day 15	-5.95 (59.07)	-13.19 (54.16)	-20.29 (39.59)	-11.13 (74.79)	-7.70 (63.59)
Uric acid, Day 22	-1.40 (46.23)	-3.55 (53.46)	-21.63 (52.20)	-13.61 (57.87)	-13.88 (70.17)
Uric acid, Day 28	5.69 (50.16)	6.20 (74.17)	-10.73 (41.62)	-6.00 (61.23)	-18.05 (82.41)
Uric acid, Day 35	2.30 (55.55)	-8.63 (57.75)	-4.51 (56.60)	12.03 (59.59)	-2.45 (57.67)

21. Primary Outcome

Title	Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Description	Assessment for lipid profile was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. The parameters included high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol and triglycerides. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
HDL, Day 8	-0.02 (0.14)	0.01 (0.19)	0.02 (0.19)	0.05 (0.18)	-0.03 (0.17)
HDL, Day 15	-0.02 (0.21)	0.01 (0.17)	-0.01 (0.20)	0.08 (0.21)	-0.03 (0.16)
HDL, Day 22	-0.03 (0.21)	0.02 (0.23)	0.02 (0.19)	0.05 (0.14)	-0.04 (0.18)
HDL, Day 28	-0.04 (0.24)	-0.02 (0.20)	-0.04 (0.20)	0.01 (0.18)	-0.05 (0.20)
HDL, Day 35	-0.03 (0.22)	0.00 (0.17)	-0.01 (0.22)	0.05 (0.15)	-0.01 (0.18)
LDL, Day 8	-0.10 (0.57)	-0.27 (0.76)	-0.16 (0.57)	-0.19 (0.45)	-0.20 (0.51)
LDL, Day 15	-0.07 (0.53)	-0.26 (0.83)	-0.23 (0.76)	-0.22 (0.61)	-0.26 (0.59)
LDL, Day 22	-0.02 (0.68)	-0.34 (0.67)	-0.14 (0.88)	-0.23 (0.52)	-0.17 (0.74)
LDL, Day 28	-0.07 (0.69)	-0.17 (0.77)	-0.29 (0.75)	-0.28 (0.59)	-0.22 (0.86)
LDL, Day 35	-0.08 (0.71)	-0.30 (0.83)	-0.14 (0.77)	-0.15 (0.50)	-0.07 (0.86)
Total cholesterol, Day 8	-0.16 (0.62)	-0.33 (0.89)	-0.27 (0.72)	-0.38 (0.50)	-0.27 (0.59)
Total cholesterol, Day 15	-0.09 (0.71)	-0.38 (0.97)	-0.27 (0.98)	-0.35 (0.82)	-0.27 (0.72)
Total cholesterol, Day 22	-0.09 (0.92)	-0.46 (0.81)	-0.16 (1.06)	-0.49 (0.81)	-0.20 (0.88)
Total cholesterol, Day 28	-0.15 (0.97)	-0.23 (0.93)	-0.25 (0.89)	-0.55 (0.81)	-0.23 (0.92)
Total cholesterol, Day 35	-0.11 (0.98)	-0.47 (0.88)	-0.22 (1.07)	-0.41 (0.93)	-0.11 (1.04)
Triglycerides, Day 8	-0.15 (0.93)	-0.14 (1.12)	-0.22 (0.76)	-0.66 (1.33)	-0.13 (0.63)
Triglycerides, Day 15	0.04 (1.05)	-0.34 (1.36)	0.02 (1.23)	-0.50 (0.97)	0.07 (1.02)
Triglycerides, Day 22	-0.08 (1.03)	-0.36 (1.30)	-0.02 (0.97)	-0.83 (1.89)	0.08 (1.32)
Triglycerides, Day 28	-0.08 (1.06)	-0.09 (1.60)	0.22 (0.95)	-0.75 (1.91)	0.03 (1.51)
Triglycerides, Day 35	-0.02 (0.83)	-0.30 (0.81)	-0.32 (3.03)	-0.90 (2.29)	-0.19 (0.88)

22. Primary Outcome

Title	Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Description	Assessment for albumin and total protein were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Albumin, Day 8	0.29 (2.03)	0.80 (2.40)	0.78 (2.72)	0.64 (2.05)	1.02 (1.93)
Albumin, Day 15	0.80 (2.44)	1.05 (2.39)	0.29 (2.39)	0.13 (2.24)	0.53 (2.06)
Albumin, Day 22	0.67 (1.91)	0.82 (2.46)	0.10 (2.34)	0.55 (2.37)	0.40 (2.02)
Albumin, Day 28	0.45 (2.15)	0.00 (2.45)	-0.63 (2.79)	-0.32 (2.24)	-0.53 (2.40)
Albumin, Day 35	-0.02 (2.59)	-0.07 (2.08)	-0.17 (2.56)	-0.16 (2.48)	-0.21 (2.31)
Total protein, Day 8	-0.24 (3.33)	1.24 (4.39)	0.23 (4.29)	0.21 (3.15)	1.24 (4.16)
Total protein, Day 15	0.44 (4.43)	0.67 (4.68)	0.63 (4.92)	-1.24 (4.28)	-0.03 (4.38)
Total protein, Day 22	0.48 (3.21)	1.29 (5.54)	0.49 (4.90)	0.18 (3.81)	-0.03 (3.88)
Total protein, Day 28	0.21 (3.76)	0.06 (5.17)	-1.10 (5.45)	-0.63 (3.76)	-1.49 (4.48)
Total protein, Day 35	-0.05 (4.03)	-0.61 (3.94)	-0.07 (4.66)	-0.95 (4.16)	-1.57 (4.80)

23. Primary Outcome

Title	Change From Baseline in Urinalysis Parameter of Specific Gravity Over Time
Description	Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 8	-0.00 (0.01)	-0.00 (0.01)	0.00 (0.01)	-0.00 (0.01)	-0.00 (0.01)
Day 15	-0.00 (0.01)	-0.00 (0.00)	-0.00 (0.01)	-0.00 (0.01)	0.00 (0.01)
Day 22	-0.00 (0.01)	-0.00 (0.01)	0.00 (0.01)	-0.00 (0.01)	0.00 (0.01)
Day 28	0.00 (0.01)	-0.00 (0.01)	0.00 (0.01)	-0.00 (0.01)	0.00 (0.01)
Day 35	-0.00 (0.01)	-0.00 (0.01)	0.00 (0.01)	-0.00 (0.01)	-0.00 (0.01)

24. Primary Outcome

Title	Change From Baseline in Urinalysis Parameter of pH Over Time
Description	Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessment was performed on Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	43	44	42	43
Day 8	0.05 (0.34)	-0.05 (0.38)	-0.02 (0.35)	0.00 (0.43)	0.10 (0.51)
Day 15	0.05 (0.35)	-0.04 (0.45)	-0.05 (0.57)	0.11 (0.47)	0.08 (0.62)
Day 22	0.14 (0.41)	-0.03 (0.50)	0.01 (0.55)	0.05 (0.40)	-0.03 (0.48)
Day 28	0.28 (0.66)	-0.09 (0.43)	0.00 (0.59)	0.03 (0.37)	0.04 (0.63)
Day 35	0.06 (0.48)	-0.15 (0.37)	-0.12 (0.55)	0.01 (0.38)	0.07 (0.52)

25. Primary Outcome

Title	Area Under Plasma Concentration Curve From Time 0 to Last Measurable Time Point (AUC 0-t), From Time 0 to Infinity (AUC 0-infinity) and From Time 0 to Trough Concentration (AUC 0-τ) of SRT2104 on Day 1 and Day 28
Description	The pre-dose blood samples were collected within one hour prior to study medication administration. The post-dose blood samples were collected within 2 minutes of the scheduled time. AUC values reported in the analysis of AUC 0-infinity of Day 28 versus Day 1 included AUC 0-infinity on Day 1 and AUC 0-τ on Day 28. Participants fasted for at least 10 hour overnight on Day 1, 2 and 29. The AUC 0-t was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. AUC0-infinity was estimated by linear trapezoidal rule and was sum of the AUC0-t and extrapolated to infinity by dividing the estimated last measurable plasma concentration by elimination rate constant lambda z. Where lambda z is the terminal phase rate constant estimated by linear regression analysis of the log10 transformed concentration-time data after each single dose. The AUC0-infinity was the sum of the estimated and extrapolated parts.
Time Frame	Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Population defined as all participants who received SRT2104, had sufficient blood samples taken to obtain a plasma concentration time profile and who did not violate the protocol in such a way that it could influence the statistical analysis. Only those participants available at the specified time points were analyzed.

Arm/Group Title	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	44	42	43
Day 1, AUC 0-t	1045.8420 (978.3355)	2153.0075 (1835.6039)	2375.3150 (2285.7123)	2859.5465 (2916.4783)
Day 28, AUC 0-t	1549.6139 (1450.1354)	2731.6308 (2337.0839)	3109.8747 (2948.2780)	4380.2204 (4476.9484)
Day 1, AUC 0-infinity	1564.4905 (1119.3480)	2797.6930 (2287.3141)	3080.6902 (2532.8224)	3837.1384 (4078.6970)
Day 28, AUC 0-infinity	2289.6858 (1876.6537)	4634.3397 (5387.2429)	4960.3422 (3914.0260)	8159.4534 (7592.2760)
Day 28, AUC 0-τ	1620.5989 (1431.4150)	2731.6231 (2337.0919)	3212.6640 (2924.1860)	4584.5679 (4502.8752)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	Day 28 versus Day 1 for AUC 0-t of SRT2104 0.25 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	168.40
	Confidence Interval	(2-Sided) 90%; 123.87 to 228.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding confidence interval (CI) were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	Day 28 versus Day 1 for AUC 0-infinity of SRT2104 0.25 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	110.88
	Confidence Interval	(2-Sided) 90%; 88.18 to 139.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI. AUC values included in the analysis were AUC 0-infinity on Day 1 and AUC 0-τ on Day 28.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SRT2104 0.25 g/Day
	Comments	Day 28 versus Day 1 for AUC 0-t of SRT2104 0.5 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	133.11
	Confidence Interval	(2-Sided) 90%; 100.55 to 176.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	SRT2104 0.25 g/Day
	Comments	Day 28 versus Day 1 for AUC 0-infinity of SRT2104 0.5 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Other
	Estimated Value	94.30
	Confidence Interval	(2-Sided) 90%; 70.31 to 126.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI. The AUC values included in the analysis were AUC 0-infinity on Day 1 and AUC 0-τ on Day 28.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	SRT2104 0.5 g/Day
	Comments	Day 28 versus Day 1 for AUC 0-t of SRT2104 1.0 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	141.63
	Confidence Interval	(2-Sided) 90%; 111.20 to 180.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	SRT2104 0.5 g/Day
	Comments	Day 28 versus Day 1for AUC 0-infinity of SRT2104 1.0 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	114.46
	Confidence Interval	(2-Sided) 90%; 85.56 to 153.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI. The AUC values included in the analysis were AUC 0-infinity on Day 1 and AUC 0-τ on Day 28.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	SRT2104 1.0 g/Day
	Comments	Day 28 versus Day 1 for AUC 0-t of SRT2104 2.0 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	167.09
	Confidence Interval	(2-Sided) 90%; 120.73 to 231.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	SRT2104 1.0 g/Day
	Comments	Day 28 versus Day 1 for AUC 0-infinity of SRT2104 2.0 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	117.73
	Confidence Interval	(2-Sided) 90%; 85.14 to 162.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI. The AUC values included in the analysis were AUC 0-infinity on Day 1 and AUC 0-τ on Day 28.

26. Primary Outcome

Title	Observed Maximum Plasma Concentration (Cmax) of SRT2104 at Day 1 and Day 28
Description	Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. On Day 1, Day 2 and Day 29, participants fasted for at least 10 hour overnight. The post-dose sample was collected within 2 minutes of the scheduled time. The first occurrence of the Cmax was determined directly from the raw concentration-time data.
Time Frame	Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	44	42	43
Day 1	178.729 (179.982)	366.694 (322.951)	336.562 (298.042)	417.832 (470.048)
Day 28	185.418 (162.500)	329.973 (266.174)	375.395 (333.188)	433.650 (461.441)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	Day 28 versus Day 1 for Cmax of SRT2104 0.25 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	122.22
	Confidence Interval	(2-Sided) 90%; 86.94 to 171.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SRT2104 0.25 g/Day
	Comments	Day 28 versus Day 1 for Cmax of SRT2104 0.5 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	94.45
	Confidence Interval	(2-Sided) 90%; 69.07 to 129.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SRT2104 0.5 g/Day
	Comments	Day 28 versus Day 1 for Cmax of SRT2104 1.0 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	114.79
	Confidence Interval	(2-Sided) 90%; 91.54 to 143.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	SRT2104 1.0 g/Day
	Comments	Day 28 versus Day 1 for Cmax of SRT2104 2.0 g/day.
	Type of Statistical Test	Other
	Comments	The analysis used an Estimation approach. No hypothesis testing was performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	120.30
	Confidence Interval	(2-Sided) 90%; 88.66 to 163.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in least squares means and corresponding CI were back-transformed to form ratio of geometric least squares means (Day 28/ Day 1) and CI.

27. Primary Outcome

Title	Time to Cmax (Tmax) at Day 1 and Day 28
Description	Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. The post-dose sample was collected within 2 minutes of the scheduled time. The time at which Cmax was observed was determined directly from the raw concentration-time data.
Time Frame	Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	44	42	43
Day 1	3.000	3.000	3.000	4.000
Day 28	3.000	3.000	3.000	3.000

28. Primary Outcome

Title	Terminal Elimination Half Life (T1/2) of SRT2104 at Day 1 and Day 28
Description	Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. The post-dose sample was collected within 2 minutes of the scheduled time. On Day 1 Day 2 and Day 29, participants fasted for at least 10 hour overnight. The t1/2 was obtained as the ratio of ln2/λz, where λz is the terminal phase rate constant estimated by linear regression analysis of the concentration-time data.
Time Frame	Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	44	42	43
Day 1	13.4184	12.1669	13.3434	9.7846
Day 28	18.0115	20.3500	18.9258	17.4548

29. Primary Outcome

Title	Apparent Total Clearance of SRT2104 From Plasma After Oral Administration (CL/F) on Day 1 and Day 28
Description	Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. The post-dose sample was collected within 2 minutes of the scheduled time. On Day 1 Day 2 and Day 29, participants fasted for at least 10 hour overnight.
Time Frame	Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	44	42	43
Day 1	494.0236 (625.5532)	621.3930 (948.1533)	1582.0131 (2707.3466)	2181.8596 (2959.1044)
Day 28	631.5519 (900.3648)	956.6848 (2117.3623)	1420.2734 (2128.7769)	1887.2455 (2883.3080)

30. Primary Outcome

Title	Apparent Volume of Distribution After Oral Administration (Vd/F) at Day 1 and Day 28
Description	Blood samples were collected on Day 1 (pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8 (pre-dose), Day 15 (pre-dose), Day 22 (pre-dose), Day 28 (pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour, 8 hour and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose). The pre-dose sample was collected within one hour prior to study medication administration. The post-dose sample was collected within 2 minutes of the scheduled time. On Day 1 Day 2 and Day 29, participants fasted for at least 10 hour overnight.
Time Frame	Day 1 (pre-dose, 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose), Day 2 (24 hour post-Day 1 dose), Day 8, 15 and 22 (pre-dose), Day 28 (pre-dose, and 15 and 30 minutes, 1, 2, 3, 4, 8 and 12 hour post-dose) and Day 29 (24 hour post-Day 28 dose)

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	44	42	43
Day 1	12921.7880 (19802.8598)	15767.2219 (29059.7570)	38320.97415 (77339.06047)	32262.5089 (45180.0346)
Day 28	17509.8071 (27627.2504)	48475.7739 (150725.4900)	56531.7676 (108327.3925)	51594.5474 (93165.0710)

31. Secondary Outcome

Title	Mean Fasting Plasma Glucose (FPG) Levels Over Time
Description	The assessments were done at Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35 weekly at central laboratory. The analysis was reported for Day 8, Day 15, Day 22, Day 28 and Day 35.
Time Frame	Up to Day 35

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
Day 8	10.46 (2.60)	10.33 (2.30)	11.10 (2.33)	10.67 (2.19)	10.37 (2.81)
Day 15	10.08 (2.46)	10.52 (2.40)	10.51 (2.39)	10.37 (2.30)	10.41 (2.81)
Day 22	10.03 (2.03)	10.31 (2.66)	11.24 (2.17)	10.59 (2.35)	10.56 (2.84)
Day 28	9.60 (2.02)	10.21 (2.12)	10.49 (2.22)	10.32 (2.16)	10.05 (2.38)
Day 35	10.10 (2.41)	10.10 (2.21)	9.92 (2.04)	9.51 (2.62)	9.03 (1.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 8 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.997
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 8 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.581
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 8 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.987
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 8 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 15 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.850
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 15 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.843
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 15 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.961
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 15 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.939
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 22 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.966
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 22 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.075
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 22 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.700
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 22 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.732
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 28 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.552
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 28 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.196
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 28 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.393
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 28 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.775
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 35 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 35 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.989
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 35 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.603
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 35 for FPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.108
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

32. Secondary Outcome

Title	Change From Baseline in FPG Levels Over Time
Description	The assessments were done at Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35 weekly at central laboratory. Baseline was defined as the assessment done on Day 1. The analysis was reported for Day 8, Day 15, Day 22, Day 28 and Day 35. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
Day 8	-0.30 (2.20)	-1.00 (3.23)	0.16 (2.06)	-0.41 (2.77)	0.17 (2.05)
Day 15	-0.72 (2.45)	-0.91 (2.61)	-0.41 (2.35)	-0.64 (2.78)	0.17 (2.72)
Day 22	-0.74 (2.48)	-1.06 (3.63)	0.28 (2.79)	-0.47 (2.90)	0.40 (2.71)
Day 28	-1.17 (2.42)	-1.11 (3.45)	-0.52 (2.60)	-0.97 (2.83)	-0.15 (2.38)
Day 35	-0.73 (2.70)	-0.94 (2.47)	-1.24 (3.07)	-1.52 (3.29)	-1.14 (2.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPG on Day 8.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.525
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPG on Day 8.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.818
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPG on Day 8.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPG on Day 8.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.809
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPG on Day 15.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.993
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPG on Day 15.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.954
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPG on Day 15.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPG on Day 15.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.344
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPG on Day 22.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.968
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPG on Day 22.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.316
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPG on Day 22.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.984
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPG on Day 22.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.235
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPG on Day 28.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPG on Day 28.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.656
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPG on Day 28.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.994
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPG on Day 28.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.285
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPG on Day 35.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.992
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPG on Day 35.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.822
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPG on Day 35.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.538
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPG on Day 35.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.907
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

33. Secondary Outcome

Title	Mean Fasting Plasma Insulin (FPI) Levels Over Time
Description	The assessments were done at Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35 weekly at central laboratory. The analysis was reported for Day 8, Day 15, Day 22, Day 28 and Day 35.
Time Frame	Up to Day 35

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
Day 8	89.9 (59.63)	92.3 (95.57)	83.8 (52.19)	74.5 (61.77)	74.4 (51.36)
Day 15	90.0 (70.89)	78.4 (93.50)	80.4 (45.86)	80.5 (76.39)	79.3 (89.05)
Day 22	98.7 (98.55)	74.3 (93.51)	81.8 (47.79)	78.8 (65.46)	76.8 (57.34)
Day 28	82.4 (56.91)	91.7 (118.05)	63.7 (44.87)	63.3 (55.69)	89.2 (134.56)
Day 35	101.6 (70.49)	110.5 (157.53)	87.1 (56.22)	84.0 (78.95)	115.3 (213.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 8 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 8 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.982
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 8 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.677
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 8 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.688
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 15 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.903
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 15 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.945
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 15 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.949
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 15 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.924
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 22 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.394
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 22 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.687
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 22 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.568
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 22 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.486
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 28 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.973
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 28 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.739
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 28 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.731
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 28 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.991
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day on Day 35 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.994
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day on Day 35 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.963
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day on Day 35 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.929
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day on Day 35 for FPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.970
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

34. Secondary Outcome

Title	Change From Baseline in FPI Over Time
Description	The assessments were done at Day 1, Day 8, Day 15, Day 22, Day 28 and Day 35 weekly at central laboratory. Baseline was defined as the assessment done on Day 1. The analysis was reported for Day 8, Day 15, Day 22, Day 28 and Day 35. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 8, Day 15, Day 22, Day 28 and Day 35) values.
Time Frame	Baseline (Day 1) and up to Day 35

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
Day 8	7.2 (66.75)	12.2 (80.20)	12.3 (49.91)	12.9 (63.97)	4.7 (37.72)
Day 15	10.8 (77.13)	-6.5 (48.51)	8.1 (45.43)	18.8 (88.06)	8.3 (96.60)
Day 22	17.6 (90.89)	-4.6 (55.62)	10.6 (56.34)	20.2 (75.69)	0.3 (49.95)
Day 28	1.0 (51.66)	8.9 (95.04)	-6.9 (41.45)	4.1 (57.16)	15.2 (138.79)
Day 35	20.4 (80.92)	30.7 (103.55)	13.7 (47.92)	22.3 (79.42)	48.0 (216.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPI on Day 8.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.989
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPI on Day 8.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.989
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPI on Day 8.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.982
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPI on Day 8.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPI on Day 15.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.685
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPI on Day 15.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPI on Day 15.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.971
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPI on Day 15.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPI on Day 22.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.405
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPI on Day 22.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.975
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPI on Day 22.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPI on Day 22.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.629
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPI on Day 28.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.982
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPI on Day 28.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.982
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPI on Day 28.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPI on Day 28.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.874
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in FPI on Day 35.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.986
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in FPI on Day 35.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.997
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in FPI on Day 35.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in FPI on Day 35.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.697
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

35. Secondary Outcome

Title	Mean Post-prandial Glucose (PPG) and Post-prandial Insulin (PPI) Levels at Day 28
Description	The assessment of PPG and PPI was performed on Day 28 at 30 minutes, 60 minutes and 2 hour after the participant consumed the standardized meal (morning breakfast).
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
PPG, 30 minutes	12.91 (2.94)	12.95 (2.66)	13.58 (3.05)	13.12 (2.90)	11.41 (2.77)
PPG, 60 minutes	14.05 (3.13)	14.05 (3.57)	15.44 (3.05)	14.77 (3.16)	13.08 (3.70)
PPG, 2 hour	13.16 (4.26)	13.15 (3.55)	14.74 (3.15)	13.90 (3.60)	13.61 (4.43)
PPI, 30 minutes	237.6 (222.95)	217.2 (198.91)	188.3 (172.53)	160.2 (153.46)	163.0 (179.83)
PPI, 60 minutes	298.1 (232.43)	285.4 (339.90)	223.0 (167.72)	189.2 (145.83)	226.6 (200.82)
PPI, 2 hour	224.4 (129.69)	215.0 (309.78)	192.5 (132.93)	183.8 (160.20)	206.4 (202.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at 30 minutes for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at 30 minutes for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.812
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at 30 minutes for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.996
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at 30 minutes for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.198
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at 60 minutes for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at 60 minutes for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.358
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at 60 minutes for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.852
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at 60 minutes for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.678
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at 2 hour for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at 2 hour for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.191
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at 2 hour for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.805
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at 2 hour for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.960
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at 30 minutes for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.985
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at 30 minutes for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.733
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at 30 minutes for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.365
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at 30 minutes for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.413
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at 60 minutes for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.765
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at 60 minutes for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.434
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at 60 minutes for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.184
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at 60 minutes for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.142
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at 2 hour for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at 2 hour for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.876
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at 2 hour for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.756
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at 2 hour for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.983
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

36. Secondary Outcome

Title	Change From Baseline in PPG and PPI Levels at Day 28
Description	The assessment of PPG and PPI was performed at 30 minutes, 60 minutes and 2 hour after the participant consumed the standardized meal (morning breakfast) on Day 1 and Day 28. Baseline for PPG was defined as the assessment value of FPG done on Day 1 and Baseline for PPI was defined as the assessment value of FPI done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (30 min, 60 min and 2 h at Day 28) values.
Time Frame	Baseline (Day 1) and Day 28

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
PPG, 30 minutes	3.38 (2.85)	2.82 (2.40)	3.40 (2.52)	3.14 (1.75)	2.00 (2.17)
PPG, 60 minutes	4.53 (2.86)	3.92 (3.55)	5.12 (2.57)	4.74 (2.34)	3.68 (3.08)
PPG, 2 hour	3.56 (3.37)	2.93 (3.33)	4.23 (2.88)	3.66 (2.54)	3.47 (3.44)
PPI, 30 minutes	162.4 (204.29)	108.7 (136.13)	119.2 (157.32)	94.9 (109.96)	57.4 (73.07)
PPI, 60 minutes	222.9 (206.99)	176.9 (278.91)	153.9 (146.74)	128.4 (105.95)	121.0 (95.22)
PPI, 2 hour	142.0 (113.58)	123.3 (253.84)	128.7 (106.87)	120.5 (129.95)	117.3 (127.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in PPG at 30 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.809
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in PPG at 30 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in PPG at 30 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.989
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in PPG at 30 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.130
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in PPG at 60 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.870
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in PPG at 60 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.864
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in PPG at 60 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.997
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in PPG at 60 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.682
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in PPG at 2 hour.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.798
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in PPG at 2 hour.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.730
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in PPG at 2 hour.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in PPG at 2 hour.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in PPI at 30 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.464
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in PPI at 30 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.634
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in PPI at 30 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in PPI at 30 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.034
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in PPI at 60 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.765
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in PPI at 60 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.434
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in PPI at 60 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.184
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in PPI at 60 minutes.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.142
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day for change from Baseline in PPI at 2 hour.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.955
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day for change from Baseline in PPI at 2 hour.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.985
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day for change from Baseline in PPI at 2 hour.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.923
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day for change from Baseline in PPI at 2 hour.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.883
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

37. Secondary Outcome

Title	Mean Glycosylated Hemoglobin A (HbA1c) Levels on Day 28
Description	The sample for HbA1c assessment was collected on Day 28. HbA1c is used to show how well their diabetes is being controlled in participants with diabetes. The HbA1c test gives the average blood glucose levels over the pervious two to three months.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	36	42	40	40
Mean (Standard Deviation) [Percentage of HbA1c]	8.18 (0.95)	8.66 (1.00)	8.64 (0.93)	8.54 (1.16)	8.29 (0.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.118
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.119
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.293
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.966
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

38. Secondary Outcome

Title	Change From Baseline in HbA1c Levels at Day 28
Description	HbA1c is used to show how well their diabetes is being controlled in participants with diabetes. The HbA1c test gives the average blood glucose levels over the pervious two to three months. The sample for HbA1c assessment was collected on Day 1 and Day 28. Baseline value was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28) value.
Time Frame	Baseline (Day 1) and Day 28

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	43	35	42	38	40
Mean (Standard Deviation) [Percentage of HbA1c]	-0.31 (0.55)	-0.23 (0.68)	-0.05 (0.52)	0.01 (0.78)	-0.10 (0.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.940
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.197
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.097
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.404
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

39. Secondary Outcome

Title	AUC From Time 0 to 1 h (AUC 0-1) and AUC From Time 0 to 2 h (AUC 0-2) for PPG and PPI at Day 1 and Day 28
Description	The assessment of PPG and PPI was performed at 30 minutes, 60 minnutes and 2 hour after the participant consumed the standardized meal (morning breakfast) on Day 1 and Day 28. AUC with respect to these time interval was calculated using the linear trapezoidal rule by the sum of the areas between each chronological pair of assessments (using observed times) for PPG and PPI.
Time Frame	Day 1 (30 minutes, 60 minutes and 2 hour) and Day 28 (30 minutes, 60 minutes and 2 hour)

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	30	31	32	31	30
Day 1, AUC 0-1, PPG	13.10 (2.69)	14.08 (3.40)	14.28 (3.50)	14.43 (4.18)	12.68 (2.73)
Day 28, AUC 0-1, PPG	12.35 (2.45)	12.52 (2.41)	13.25 (2.58)	12.92 (2.27)	11.33 (2.63)
Day 1, AUC 0-2, PPG	27.39 (5.72)	29.35 (7.64)	29.87 (7.20)	29.95 (9.34)	26.07 (5.99)
Day 28, AUC 0-2, PPG	25.89 (5.84)	25.98 (5.64)	28.30 (5.51)	27.01 (5.11)	24.14 (6.40)
Day 1, AUC 0-1, PPI	192.4 (121.08)	211.1 (245.53)	176.6 (105.51)	168.3 (123.33)	186.0 (92.55)
Day 28, AUC 0-1, PPI	212.1 (176.25)	207.1 (202.43)	168.1 (135.71)	138.8 (120.34)	164.6 (175.64)
Day 1, AUC 0-2, PPI	423.8 (289.68)	478.8 (584.46)	418.4 (251.25)	377.6 (297.27)	385.8 (167.81)
Day 28, AUC 0-2, PPI	444.8 (332.82)	477.7 (538.49)	394.5 (276.65)	334.7 (256.51)	381.3 (378.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day of AUC 0-1 at Day 1 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2060
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day of AUC 0-1 at Day 1 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1790
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day of AUC 0-1 at Day 1 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2741
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day of AUC 0-1 at Day 1 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6001
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day of AUC 0-1 at Day 28 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6711
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day of AUC 0-1 at Day 28 for PPG.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1361
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day of AUC 0-1 at Day 28 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3369
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day of AUC 0-1 at Day 28 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0975
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day of AUC 0-2 at Day 1 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2184
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day of AUC 0-2 at Day 1 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1013
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day of AUC 0-2 at Day 1 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3286
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day of AUC 0-2 at Day 1 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5193
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day of AUC 0-2 at Day 28 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9788
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day of AUC 0-2 at Day 28 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1214
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day of AUC 0-2 at Day 28 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5751
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day of AUC 0-2 at Day 28 for PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2409
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day of AUC 0-1 at Day 1 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4829
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day of AUC 0-1 at Day 1 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7563
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day of AUC 0-1 at Day 1 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2907
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day of AUC 0-1 at Day 1 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7663
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day of AUC 0-1 at Day 28 for PPI
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5825
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day of AUC 0-1 at Day 28 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3220
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day of AUC 0-1 at Day 28 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0564
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day of AUC 0-1 at Day 28 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1960
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day of AUC 0-2 at Day 1 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5997
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day of AUC 0-2 at Day 1 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9637
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day of AUC 0-2 at Day 1 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3240
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day of AUC 0-2 at Day 1 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8440
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day of AUC 0-2 at Day 28 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6483
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day of AUC 0-2 at Day 28 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6452
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day of AUC 0-2 at Day 28 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1253
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day of AUC 0-2 at Day 28 for PPI.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2583
	Comments	No adjustments for covariates were made.
	Method	Wilcoxon test
	Comments

40. Secondary Outcome

Title	Mean Fructosamine Levels at Day 1 and Day 28
Description	Fructosamine (a glycated protein) level enables assessment of long-term glycemic control in participants with diabetes mellitus. The blood samples for fructosamine assessment was obtained at Day 1 and Day 28.
Time Frame	Day 1 and Day 28

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
Day 1	320.07 (61.28)	320.38 (49.20)	319.82 (56.73)	328.44 (62.90)	296.00 (41.86)
Day 28	305.70 (56.04)	315.97 (60.46)	330.15 (61.32)	318.63 (50.90)	285.28 (57.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at Day 1 for fructosamine.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at Day 1 for fructosamine.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at Day 1 for fructosamine.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.901
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at Day 1 for fructosamine.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.155
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at Day 28 for fructosamine.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.845
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at Day 28 for fructosamine.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.164
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at Day 28 for fructosamine.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.699
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at Day 28 for fructosamine.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.313
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

41. Secondary Outcome

Title	Change From Baseline in Fructosamine Levels at Day 28
Description	Fructosamine (a glycated protein) level enables assessment of long-term glycemic control in participants with diabetes mellitus. The blood samples for fructosamine assessment was obtained at Day 1 and Day 28. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28) value.
Time Frame	Baseline (Day 1) and Day 28

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
Mean (Standard Deviation) [mmol per liter]	-14.37 (41.18)	-6.67 (40.27)	9.76 (62.77)	-4.68 (44.64)	-2.14 (48.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.896
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.080
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.792
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.645
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

42. Secondary Outcome

Title	Mean Homeostatic Model Assessment-insulin Resistance (HOMA-IR) at Day 1 and Day 28
Description	HOMA-IR was derived from FPG and FPI as: FPI (micro units [mU]/mL)*FPG (mmol per liter) divided by 22.5. HOMA-IR was calculated from the Day 1 and Day 28 FPG and FPI values at Day 1 and Day 28.
Time Frame	Day 1 and Day 28

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
Day 1	5.4 (3.98)	5.7 (5.45)	5.2 (5.20)	4.1 (3.31)	5.0 (3.75)
Day 28	4.9 (3.56)	5.9 (7.28)	3.9 (2.55)	4.0 (3.66)	5.9 (10.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at Day 1 for HOMA-IR.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.992
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at Day 1 for HOMA-IR.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at Day 1 for HOMA-IR.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.548
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at Day 1 for HOMA-IR.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.989
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at Day 28 for HOMA-IR.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.877
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at Day 28 for HOMA-IR.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.887
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at Day 28 for HOMA-IR.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.916
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at Day 28 for HOMA-IR.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.860
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

43. Secondary Outcome

Title	Change From Baseline in HOMA-IR at Day 28
Description	HOMA-IR was derived from FPG and FPI as: FPI (mU/mL)*FPG (mmol per liter) divided by 22.5. HOMA-IR was calculated from the Day 1 and Day 28 FPG and FPI values at Day 1 and Day 28. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28) value.
Time Frame	Baseline (Day 1) and Day 28

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 minutes following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	41	34	39	35	35
Mean (Standard Deviation) [mU*mmol per liter^2]	-0.4 (3.61)	0.0 (7.26)	-0.9 (3.47)	-0.1 (3.83)	1.0 (10.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.996
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.989
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.763
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

44. Secondary Outcome

Title	Mean HOMA-percentage Cell Beta Function at Day 1 and Day 28
Description	HOMA-percentage cell beta function was derived from FPG and FPI as: 20*FPI (mU/mL) divided by FPG (mmol per liter) minus 3.5. HOMA-percentage cell beta function was calculated from the Day 1 and Day 28 FPG and FPI values at Day 1 and Day 28.
Time Frame	Day 1 and Day 28

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	46	45	46	45	45
Day 1	38.3 (38.15)	31.8 (46.38)	31.2 (35.46)	27.2 (21.39)	30.2 (23.03)
Day 28	42.9 (34.71)	42.9 (57.90)	32.6 (34.57)	28.4 (26.48)	40.9 (48.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at Day 1 for HOMA-percentage of beta cell function.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.810
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at Day 1 for HOMA-percentage of beta cell function.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.753
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at Day 1 for HOMA-percentage of beta cell function.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.404
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at Day 1 for HOMA-percentage of beta cell function.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.671
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments	Placebo versus SRT2104 0.25 g/day at Day 28 for HOMA-percentage of beta cell function.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments	Placebo versus SRT2104 0.5 g/day at Day 28 for HOMA-percentage of beta cell function.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.622
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments	Placebo versus SRT2104 1.0 g/day at Day 28 for HOMA-percentage of beta cell function.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.332
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments	Placebo versus SRT2104 2.0 g/day at Day 28 for HOMA-percentage of beta cell function.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.998
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

45. Secondary Outcome

Title	Change From Baseline in HOMA-percentage of Beta Cell Function at Day 28
Description	HOMA-percentage cell beta function was derived from FPG and FPI as: 20*FPI (mU/mL) divided by FPG (mmol per liter) minus 3.5. HOMA-percentage cell beta function was calculated from the Day 1 and Day 28 FPG and FPI values at Day 1 and Day 28. Baseline was defined as assessment done on Day 1. Baseline was defined as the assessment done on Day 1. The change from Baseline was calculated by subtracting the Baseline value (Day 1) from the individual post-Baseline (Day 28) value.
Time Frame	Baseline (Day 1) and Day 28

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	SRT2104 0.25 g/Day	SRT2104 0.5 g/Day	SRT2104 1.0 g/Day	SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.	Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
Measure Participants	41	34	39	35	35
Mean (Standard Deviation) [Percentage of beta cell function]	5.8 (34.02)	8.5 (42.09)	2.3 (17.87)	3.1 (26.45)	7.6 (51.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.25 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.994
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 0.5 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.979
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 1.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.993
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, SRT2104 2.0 g/Day
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Analysis was performed using ANOVA with Dunnett's test using the placebo group as the control, a 2-sided alpha of 0.05 was set as the significance threshold. No adjustments for covariates were made.
	Method	ANOVA
	Comments	Dunnett's test was used to control for inflation of alpha due to multiple comparisons, using the placebo group as the control.

Adverse Events

Time Frame	AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Adverse Event Reporting Description	Safety Analysis Set Population was used.
Arm/Group Title	Placebo		SRT2104 0.25 g/Day		SRT2104 0.5 g/Day		SRT2104 1.0 g/Day		SRT2104 2.0 g/Day
Arm/Group Description	Participants received oral dose of matching placebo to SRT2104 capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.		Participants received oral dose of SRT2104 0.25 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.		Participants received oral dose of SRT2104 0.5 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.		Participants received oral dose of SRT2104 1.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.		Participants received oral dose of SRT2104 2.0 g/day capsule, once daily for 28 consecutive days. The study medication was administered as 8 capsules per day to maintain the blinding, at the same time every morning, approximately 15-30 min following the start of meal consumption with 1 to 2 glasses of water.
All Cause Mortality
	Placebo		SRT2104 0.25 g/Day		SRT2104 0.5 g/Day		SRT2104 1.0 g/Day		SRT2104 2.0 g/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/43 (0%)		1/44 (2.3%)		0/42 (0%)		0/43 (0%)
Serious Adverse Events
	Placebo		SRT2104 0.25 g/Day		SRT2104 0.5 g/Day		SRT2104 1.0 g/Day		SRT2104 2.0 g/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		1/43 (2.3%)		1/44 (2.3%)		0/42 (0%)		0/43 (0%)
Infections and infestations
Sepsis	0/43 (0%)		0/43 (0%)		1/44 (2.3%)		0/42 (0%)		0/43 (0%)
Wound infection	0/43 (0%)		0/43 (0%)		1/44 (2.3%)		0/42 (0%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/43 (0%)		1/43 (2.3%)		0/44 (0%)		0/42 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		SRT2104 0.25 g/Day		SRT2104 0.5 g/Day		SRT2104 1.0 g/Day		SRT2104 2.0 g/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/43 (16.3%)		4/43 (9.3%)		12/44 (27.3%)		5/42 (11.9%)		8/43 (18.6%)
Gastrointestinal disorders
Diarrhoea	2/43 (4.7%)		1/43 (2.3%)		4/44 (9.1%)		1/42 (2.4%)		2/43 (4.7%)
Nausea	2/43 (4.7%)		3/43 (7%)		4/44 (9.1%)		1/42 (2.4%)		2/43 (4.7%)
General disorders
Asthenia	1/43 (2.3%)		1/43 (2.3%)		4/44 (9.1%)		0/42 (0%)		0/43 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	3/43 (7%)		1/43 (2.3%)		3/44 (6.8%)		4/42 (9.5%)		4/43 (9.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.