| Outcome Measures: |
Primary: The areas under the glucose concentration time curve from time 0 (dosing) to 2 hours post-dose (AUC 0-2h, glucose) obtained during an oral glucose tolerance test (OGTT) on days 28 and 42., AUC 0-2h, glucose was obtained pre-dose (Day -1), at the end of the dosing period (Day 28), and at end-of-study (Day 42). Blood samples were obtained prior to administration of 75 g of oral glucose which was administered as standard glucose beverage after an overnight fast, within 15 minutes. A peripheral blood sample was drawn from a peripheral arm vein prior to the participant consuming the beverage. Additional blood samples were drawn at 30, 60, 90, and 120 minutes after the participant had consumed the glucose beverage for the measurement of glucose, insulin and C-peptide concentrations. Blood glucose concentrations were determined with a glucose analyzer. On Day 28, on which the participant received also investigational product, the OGTT had to be performed prior to consumption of standard meal and administration of investigational product., Day 28 and Day 42|The areas under the serum insulin concentration time curve from time 0 (dosing) to 2 hours post-dose (AUC 0-2h, insulin) obtained during OGTT, on days 28 and 42., AUC 0-2h, insulin was obtained pre-dose (Day -1), at the end of the dosing period (Day 28), and at end-of-study (Day 42). Blood samples were obtained prior to administration of 75 g of oral glucose which was administered as standard glucose beverage after an overnight fast, within 15 minutes. A peripheral blood sample was drawn from a peripheral arm vein prior to the participant consuming the beverage. Additional blood samples were drawn at 30, 60, 90, and 120 minutes after the participant had consumed the glucose beverage for the measurement of glucose, insulin and C-peptide concentrations. Blood glucose concentrations were determined with a glucose analyzer. On Day 28, on which the participant received also investigational product, the OGTT had to be performed prior to consumption of standard meal and administration of investigational product.unit of measurement was microunits×hours per milliliter, Day 28 and 42|Measurement of insulin sensitivity consisting of the insulin sensitivity index (ISIest) obtained during OGTT., Stumvoll Index: ISIest was obtained pre-dose (Day -1), at the end of the dosing period (Day 28), and at end-of-study (Day 42). Blood samples were obtained prior to administration of 75 g of oral glucose which was administered as standard glucose beverage after an overnight fast, within 15 minutes. ISI is based on insulin and glucose levels in a fasting state during OGTT and is calculated as: ISI (Matsuda) = 10000/√ G0 X I0 X Gmean X Imean where G0 - fasting plasma glucose (mg/dL) I0 - fasting plasma insulin (milliinternational units (miU)/L) Gmean - mean plasma glucose during OGTT (mg/dL) Imean - mean plasma insulin during OGTT (mIU/L). Unit of measure was (Deciliter × liter)(mg × milliinternational units), Up to Day 42|Measurement of insulin sensitivity consisting of the composite whole body sensitivity index (ISIcomposite) obtained during OGTT, ISI is based on insulin and glucose levels in a fasting state during an oral glucose tolerance test (OGTT) and is calculated as: ISI (Matsuda) = 10000/√ G0 X I0 X Gmean X Imean where G0 - fasting plasma glucose (mg/dL) I0 - fasting plasma insulin (mIU/L) Gmean - mean plasma glucose during OGTT (mg/dL) Imean - mean plasma insulin during OGTT (mIU/L). ISIcomposite was obtained pre-dose (Day -1), at the end of the dosing period (Day 28), and at end-of-study (Day 42)., Up to Day 42|Measurement of insulin sensitivity consisting of the hepatic insulin sensitivity (HIRI) obtained during OGTT, HIRI was obtained pre-dose (Day -1), at the end of the dosing period (Day 28), and at end-of-study (Day 42). Blood samples were obtained prior to administration of 75 g of oral glucose which was administered as standard glucose beverage after an overnight fast, within 15 minutes. A peripheral blood sample was drawn from a peripheral arm vein prior to the participant consuming the beverage. Additional blood samples were drawn at 30, 60, 90, and 120 minutes after the participant had consumed the glucose beverage for the measurement of glucose, insulin and C-peptide concentrations. Blood glucose concentrations were determined with a glucose analyzer. On Day 28, on which the participant received also investigational product, the OGTT had to be performed prior to consumption of standard meal and administration of investigational product. Unit of measure was millimole × hour per liter)×(milliunits × hour per liter \[mmol\*h/L)\*(mU\*h/L\], Up to Day 42|Measurement of insulin sensitivity consisting of the muscular insulin sensitivity (MISI) obtained during OGTT., MISI was obtained pre-dose (Day -1), at the end of the dosing period (Day 28), and at end-of-study (Day 42). Blood samples were obtained prior to administration of 75 g of oral glucose which was administered as standard glucose beverage after an overnight fast, within 15 minutes. A peripheral blood sample was drawn from a peripheral arm vein prior to the participant consuming the beverage. Additional blood samples were drawn at 30, 60, 90, and 120 minutes after the participant had consumed the glucose beverage for the measurement of glucose, insulin and C-peptide concentrations. Blood glucose concentrations were determined with a glucose analyzer. On Day 28, on which the participant received also investigational product, the OGTT had to be performed prior to consumption of standard meal and administration of investigational product. Unit of measure was milligram per deciliter per minute per milliunits per liter (mg/dL/min/mU/L)., Up to Day 42|Measurement of insulin sensitivity consisting of the insulin resistance index obtained during OGTT, Measurement of insulin sensitivity consisting of the insulin resistance index obtained during OGTT was not collected., Up to Da y 42|Measurement of insulin sensitivity consisting of the beta cell function based on homeostasis model assessment :HOMA-IR, obtained during OGTT, HOMA-IR was obtained pre-dose (Day -1), at the end of the dosing period (Day 28), and at end-of-study (Day 42). Blood samples were obtained prior to administration of 75 g of oral glucose which was administered as standard glucose beverage after an overnight fast, within 15 minutes. A peripheral blood sample was drawn from a peripheral arm vein prior to the participant consuming the beverage. Additional blood samples were drawn at 30, 60, 90, and 120 minutes after the participant had consumed the glucose beverage for the measurement of glucose, insulin and C-peptide concentrations. Blood glucose concentrations were determined with a glucose analyzer. On Day 28, on which the participant received also investigational product, the OGTT had to be performed prior to consumption of standard meal and administration of investigational product., Up to Day 42|Measurement of insulin sensitivity consisting of the beta cell function based on homeostasis model assessment : HOMA-%B, obtained during OGTT., HOMA-%B was obtained pre-dose (Day -1), at the end of the dosing period (Day 28), and at end-of-study (Day 42). Blood samples were obtained prior to administration of 75 g of oral glucose which was administered as standard glucose beverage after an overnight fast, within 15 minutes. A peripheral blood sample was drawn from a peripheral arm vein prior to the participant consuming the beverage. Additional blood samples were drawn at 30, 60, 90, and 120 minutes after the participant had consumed the glucose beverage for the measurement of glucose, insulin and C-peptide concentrations. Blood glucose concentrations were determined with a glucose analyzer. On Day 28, on which the participant received also investigational product, the OGTT had to be performed prior to consumption of standard meal and administration of investigational product., Up to Day 42|Measurement of insulin sensitivity consisting of the quantitative insulin sensitivity check index (QUICKI) obtained during OGTT., QUICKI was obtained pre-dose (Day -1), at the end of the dosing period (Day 28), and at end-of-study (Day 42). Blood samples were obtained prior to administration of 75 g of oral glucose which was administered as standard glucose beverage after an overnight fast, within 15 minutes. A peripheral blood sample was drawn from a peripheral arm vein prior to the participant consuming the beverage. Additional blood samples were drawn at 30, 60, 90, and 120 minutes after the participant had consumed the glucose beverage for the measurement of glucose, insulin and C-peptide concentrations. Blood glucose concentrations were determined with a glucose analyzer. On Day 28, on which the participant received also investigational product, the OGTT had to be performed prior to consumption of standard meal and administration of investigational product., Up to Day 42|Determination of sensitivity and metabolic clearance consisting of the insulin sensitive index (SI), Obtained during an hyperinsulinemic euglycemic glucose clamp (HEGC), A HEGC was carried out at Day 0, 29 and 43. HEGC was performed in participants who developed coagulation abnormalities during the study. Prior to the start of the HEGC procedure, participants were instructed to refrain from alcohol and caffeine for at least 48 hours before each inpatient visit and from exercise at least 24 hours before each inpatient visit. In the evening of the day prior to the HEGC procedure, the participants received a standard dinner at approximately 19:00 hours. Afterwards, the participants remained fasting until the end of the HEGC procedure at approximately 16:00 hours the next day. The HEGC procedure consisted of three phases: Blood glucose adjustment, Insulin infusion step 1, Insulin infusion step 2. The last 60 min of the two insulin infusion steps were defined as "steady state period 1" (SS1) and "steady state period 2" (SS2). unit of measure was Milliliter per minute permeters squared per micro units (mL/min/m2/mcU/mL)., Up to Day 43|Determination of insulin sensitivity during first (M1) and second (M2) insulin infusion step., M1 and M2 was carried out at Day 0, 29 and 43. HEGC was performed in participants who developed coagulation abnormalities during the study. Prior to the start of the HEGC procedure, participants were instructed to refrain from alcohol and caffeine for at least 48 hours before each inpatient visit and from exercise at least 24 hours before each inpatient visit. In the evening of the day prior to the HEGC procedure, the participants received a standard dinner at approximately 19:00 hours. Afterwards, the participants remained fasting until the end of the HEGC procedure at approximately 16:00 hours the next day. The HEGC procedure consisted of three phases: Blood glucose adjustment, Insulin infusion step 1, Insulin infusion step 2. The last 60 min of the two insulin infusion steps were defined as "steady state period 1" (SS1) and "steady state period 2" (SS2). Unit of measure was milligrams per minute per kilograms (mg/min/kg)., Up to Day 43|Insulin sensitivity in relation to mean insulin infusion concentration (M/I1 and M/I2) ,Obtained during HEGC, M/I1 and M/I2 was carried out at Day 0, 29 and 43. HEGC was performed in participants who developed coagulation abnormalities during the study. Prior to the start of the HEGC procedure, participants were instructed to refrain from alcohol and caffeine for at least 48 hours before each inpatient visit and from exercise at least 24 hours before each inpatient visit. In the evening of the day prior to the HEGC procedure, the participants received a standard dinner at approximately 19:00 hours. Afterwards, the participants remained fasting until the end of the HEGC procedure at approximately 16:00 hours the next day. The HEGC procedure consisted of three phases: Blood glucose adjustment, Insulin infusion step 1, Insulin infusion step 2. The last 60 min of the two insulin infusion steps were defined as "steady state period 1" (SS1) and "steady state period 2" (SS2). milligrams per minute per kilograms per microunits per milliliter (mg/min/kg/μU/mL)., Up to Day 43|Metabolic clearance rate during first and second insulin infusion step (MCR1, MCR2) on Day 29, and 43, MCR1, MCR2 was carried out at Day 0, 29 and 43. HEGC was performed in participants who developed coagulation abnormalities during the study. Prior to the start of the HEGC procedure, participants were instructed to refrain from alcohol and caffeine for at least 48 hours before each inpatient visit and from exercise at least 24 hours before each inpatient visit. In the evening of the day prior to the HEGC procedure, the participants received a standard dinner at approximately 19:00 hours. Afterwards, the participants remained fasting until the end of the HEGC procedure at approximately 16:00 hours the next day. The HEGC procedure consisted of three phases: Blood glucose adjustment, Insulin infusion step 1, Insulin infusion step 2. The last 60 min of the two insulin infusion steps were defined as "steady state period 1" (SS1) and "steady state period 2" (SS2). Unit of measure was kilograms per milliliters per kilo calories (kg/mL/kcal), Up to Day 43|Variables of metabolic clearance rate including M1ree and M2ree., M1ree and M2ree was carried out at Day 0, 29 and 43. HEGC was performed in participants who developed coagulation abnormalities during the study. Prior to the start of the HEGC procedure, participants were instructed to refrain from alcohol and caffeine for at least 48 hours before each inpatient visit and from exercise at least 24 hours before each inpatient visit. In the evening of the day prior to the HEGC procedure, the participants received a standard dinner at approximately 19:00 hours. Afterwards, the participants remained fasting until the end of the HEGC procedure at approximately 16:00 hours the next day. The HEGC procedure consisted of three phases: Blood glucose adjustment, Insulin infusion step 1, Insulin infusion step 2. The last 60 min of the two insulin infusion steps were defined as "steady state period 1" (SS1) and "steady state period 2" (SS2)., Up to Day 43|Variables of metabolic clearance rate including MCR1ree and MCR2ree ., MCR1ree and MCR2ree was carried out at Day 0, 29 and 43. HEGC was performed in participants who developed coagulation abnormalities during the study. Prior to the start of the HEGC procedure, participants were instructed to refrain from alcohol and caffeine for at least 48 hours before each inpatient visit and from exercise at least 24 hours before each inpatient visit. In the evening of the day prior to the HEGC procedure, the participants received a standard dinner at approximately 19:00 hours. Afterwards, the participants remained fasting until the end of the HEGC procedure at approximately 16:00 hours the next day. The HEGC procedure consisted of three phases: Blood glucose adjustment, Insulin infusion step 1, Insulin infusion step 2. The last 60 min of the two insulin infusion steps were defined as "steady state period 1" (SS1) and "steady state period 2" (SS2)., Up to Day 43|Variables of metabolic clearance rate including M/I1ree and M/I2ree., M/I1ree and M/I2ree was carried out at Day 0, 29 and 43. HEGC was performed in participants who developed coagulation abnormalities during the study. Prior to the start of the HEGC procedure, participants were instructed to refrain from alcohol and caffeine for at least 48 hours before each inpatient visit and from exercise at least 24 hours before each inpatient visit. In the evening of the day prior to the HEGC procedure, the participants received a standard dinner at approximately 19:00 hours. Afterwards, the participants remained fasting until the end of the HEGC procedure at approximately 16:00 hours the next day. The HEGC procedure consisted of three phases: Blood glucose adjustment, Insulin infusion step 1, Insulin infusion step 2. The last 60 min of the two insulin infusion steps were defined as "steady state period 1" (SS1) and "steady state period 2" (SS2)., Up to Day 43|Mean steady state concentration Free fatty acids (FFA), and glycerols, Mean steady state concentration Free fatty acids and glycerols was carried out at Day 0, 29 and 43. HEGC was performed in participants who developed coagulation abnormalities during the study. Prior to the start of the HEGC procedure, participants were instructed to refrain from alcohol and caffeine for at least 48 hours before each inpatient visit and from exercise at least 24 hours before each inpatient visit. In the evening of the day prior to the HEGC procedure, the participants received a standard dinner at approximately 19:00 hours. Afterwards, the participants remained fasting until the end of the HEGC procedure at approximately 16:00 hours the next day. The HEGC procedure consisted of three phases: Blood glucose adjustment, Insulin infusion step 1, Insulin infusion step 2. The last 60 min of the two insulin infusion steps were defined as "steady state period 1" (SS1) and "steady state period 2" (SS2)., Up to Day 43|Mean C-peptide concentration (mean C-peptideSS1 and C-peptideSS2) obtained during HEGC, Mean C-peptideSS1 and C-peptideSS2 was carried out at Day 0, 29 and 43. HEGC was performed in participants who developed coagulation abnormalities during the study. Prior to the start of the HEGC procedure, participants were instructed to refrain from alcohol and caffeine for at least 48 hours before each inpatient visit and from exercise at least 24 hours before each inpatient visit. In the evening of the day prior to the HEGC procedure, the participants received a standard dinner at approximately 19:00 hours. Afterwards, the participants remained fasting until the end of the HEGC procedure at approximately 16:00 hours the next day. The HEGC procedure consisted of three phases: Blood glucose adjustment, Insulin infusion step 1, Insulin infusion step 2. The last 60 min of the two insulin infusion steps were defined as "steady state period 1" (SS1) and "steady state period 2" (SS2)., Up to Day 43|Number of participants with all adverse events (AEs) and serious adverse events (SAEs), Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition., Up to 28 days|Number of participants with hypoglycemic events, Symptomatic, symptomatic and Severe Symptomatic hypoglycemia definitions were used to analyze and report hypoglycemic events. Symptomatic hypoglycemic episodes were collected from Day 1 to Day 28 with the assistance of participants diaries. Symptomatic hypoglycemia and severe symptomatic hypoglycemia was recorded in CRFs as AEs in all cases., Up to Day 28|Number of participants with abnormal Physical examination findings, A complete physical examination, including an ophthalmological examination to rule out diabetic neuropathy, was performed at screening. A symptom-driven, directed physical examination was performed also pre dosing (Day-2), during the dosing period (Day 14 and 27) and after dosing (Day 41). Number of participants with abnormal physical findings was reported., Up to Day 41|Change from baseline in Vital signs-systolic blood pressure (SBP) and diastolic blood pressure (DBP)., SBP and DBP were investigated at screening, pre-dosing (Day -2), during the dosing period (Day 1, 14 and 27) and at end of dosing follow-up period/end-of-study (Day 41 and 43). At Day 1 the vital signs were collected pre-dose (baseline values) and 3 hours post-dose. Day 0 was Baseline and change from Baseline was a value at study day subtracted by value at baseline., Up to Day 43|Change from baseline in Vital signs-Heart rate, Heart rate was investigated at screening, pre-dosing (Day -2), during the dosing period (Day 1, 14 and 27) and at end of dosing follow-up period/end-of-study (Day 41 and 43). At Day 1 the vital signs were collected pre-dose (baseline values) and 3 hours post-dose. Day 0 was Baseline and change from Baseline was a value at study day subtracted by value at baseline., Up to Day 43|Change from baseline in Vital signs-Respiratory rate, Respiratory rate was investigated at screening, pre-dosing (Day -2), during the dosing period (Day 1, 14 and 27) and at end of dosing follow-up period/end-of-study (Day 41 and 43). At Day 1 the vital signs were collected pre-dose (baseline values) and 3 hours post-dose. Day 0 was Baseline and change from Baseline was a value at study day subtracted by value at baseline., Up to Day 43|Change from baseline in Vital signs-Temperature., Up to Day 43|Number of participants with abnormal electrocardiogram (ECG) recordings, A 12-lead ECG was recorded at screening, pre-dose (Day -2), at the beginning and end of the dosing period (Day 1 and 27) and at the end of the dosing follow-up period/end-of study (Day 41 and 43). Number of participants with abnormal ECG findings was reported., Up to Day 43|Mean hematology parameters including white blood cell (WBC) and platelets count, Blood samples for assessment of WBC and platelet count was collected at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean hematology parameters including WBC Differential count and Red cell distribution width (RDW), Blood samples for assessment of WBC differential count and RDW was collected at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean hematology parameters including Hemoglobin (Hb) and Mean corpuscular hemoglobin concentration (MCHC), Blood samples for assessment of Hb and MCHC was collected at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean hematology parameters including: hematocrit count, Blood samples for assessment of hematocrit count was collected at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean hematology parameters including corpuscular volume (MCV), Blood samples for assessment of MCV was collected at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean hematology parameters including corpuscular hemoglobin (MCH), Blood samples for assessment of MCH was collected at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean hematology parameters including Red Blood Cells (RBCs) count, Blood samples for assessment of RBC count was collected at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Summary of urinalysis data: PH, Samples for pH assessment were collected at screening, Day -1, 14, 28 and 42. Unscheduled and control assessments were not included in the analysis. Data for mean and standard deviation was presented., Up to Day 42|Number of participants with urinalysis, Data for urinalysis was collected at screening, Day -1, 14, 28 and 42. Data for participants with positive and negative urinalysis result was presented. Unscheduled and control assessments were not included in the analysis., Up to Day 42|Mean clinical chemistry parameters including calcium, chloride, magnesium, potassium, sodium, bicarbonate, phosphate, glucose, urea and blood urea, Clinical chemistry assessment for calcium, chloride, magnesium, potassium, sodium, bicarbonate, phosphate, glucose, urea ,blood urea was done at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean clinical chemistry parameters including direct bilirubin, indirect bilirubin, total bilirubin ,uric acid, Clinical chemistry assessment for direct bilirubin, indirect bilirubin, total bilirubin and uric acid was done at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean clinical chemistry parameters including alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransaminase (AST), Lactate dehydrogenase (LDH), Creatine kinase, Clinical chemistry assessment for ALP, ALT, AST, LDH and creatine kinase was done at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean clinical chemistry parameters including albumin, Clinical chemistry assessment for albumin was done at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42|Mean clinical chemistry parameters including serum creatinine, Clinical chemistry assessment for serum creatinine was done at screening, Day -1, 14, 28 and 42. Data for mean and standard deviation was presented., Up to Day 42 | Secondary: The area under the plasma concentration time curve of SRT2104 from time 0 (dosing) to 24 hours post-dose (AUC 0-24h), Approximately 90 mL of blood was collected throughout duration of the trial for determination of SRT2104 in plasma. Samples were collected on Days 1 and 28 at pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, and 24 hours and for analysis. Blood samples were drawn via an indwelling cannula on days with multiple samples. unit of measure was nanograms × hours per milliliter ( ng\*h/mL), Day 1 and 28 at pre-dose, and at 15, 30 minutes,1, 2, 3, 4, 8, 12 and 24 hours|The area under the plasma concentration time curve of SRT2104 from time 0 to infinity (AUC 0-∞), The AUC (from zero to infinity) represents the total drug exposure over time. Approximately 90 mL of blood was collected throughout duration of the trial for determination of SRT2104 in plasma. Samples were collected on Days 1 and 28 at pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, and 24 hours and for analysis. Blood samples were drawn via an indwelling cannula on days with multiple samples., Day 1 and 28 at pre-dose, and at 15, 30 minutes,1, 2, 3, 4, 8, 12 and 24 hours|Mean maximum plasma concentration of SRT2104 (Cmax), Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose. Approximately 90 mL of blood was collected throughout duration of the trial for determination of SRT2104 in plasma. Samples were collected on Days 1 and 28 at pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, and 24 hours and for analysis. Blood samples were drawn via an indwelling cannula on days with multiple samples., Day 1 and 28 at pre-dose, and at 15, 30 minutes,1, 2, 3, 4, 8, 12 and 24 hours|Mean time to maximum plasma SRT2104 concentration (tmax), tmax is the term used in pharmacokinetics to describe the time at which the Cmax is observed Approximately 90 mL of blood was collected throughout duration of the trial for determination of SRT2104 in plasma. Samples were collected on Days 1 and 28 at pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, and 24 hours and for analysis. Blood samples were drawn via an indwelling cannula on days with multiple samples., Day 1 and 28 at pre-dose, and at 15, 30 minutes,1, 2, 3, 4, 8, 12 and 24 hoursDay 1, 2, 28, and 29|Mean Terminal elimination rate constant of SRT2104 (ƛz), Approximately 90 mL of blood was collected throughout duration of the trial for determination of SRT2104 in plasma. Samples were collected on Days 1 and 28 at pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, and 24 hours and for analysis. Blood samples were drawn via an indwelling cannula on days with multiple samples., Day 1 and 28 at pre-dose, and at 15, 30 minutes,1, 2, 3, 4, 8, 12 and 24 hours|Mean terminal plasma elimination half time (t1/2) of SRT2104., terminal plasma elimination half time (t1/2) was derived from plasma concentration versus time data. (t1/2) was the time required for one half of the total amount of administered drug to be eliminated from the body. Approximately 90 mL of blood was collected throughout duration of the trial for determination of SRT2104 in plasma. Samples were collected on Days 1 and 28 at pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, and 24 hours and for analysis. Blood samples were drawn via an indwelling cannula on days with multiple samples., Day 1 and 28 at pre-dose, and at 15, 30 minutes,1, 2, 3, 4, 8, 12 and 24 hours|Energy expenditure (indirect calorimetry) parameters-Oxygen consumption (% O2) at ss1 and ss2, Oxygen consumption was reported using indirect calorimetry. Indirect calorimetry was performed using Quark RMR (COSMED, Rome, Italy) on Day 0, 29 and 43 during the HEGC procedure for four 30-minute sessions at time points -570 min to -540 min (baseline), -40 min to -10 min (end of blood glucose adjustment phase), 210 min to 240 min (end of SS1), 450 min to 480 min (end of SS2)., Up to Day 43|Energy expenditure (indirect calorimetry) parameters- Carbon dioxide production(CO2) at ss1 and ss2, Carbon dioxide production was reported using indirect calorimetry. Indirect calorimetry was performed using Quark RMR (COSMED, Rome, Italy) on Day 0, 29 and 43 during the HEGC procedure for four 30-minute sessions at time points -570 min to -540 min (baseline), -40 min to -10 min (end of blood glucose adjustment phase), 210 min to 240 min (end of SS1), 450 min to 480 min (end of SS2)., Up to Day 43|Energy expenditure (indirect calorimetry) parameters-Resting energy expenditure (ree) at ss1 and ss2, Resting energy expenditure was reported using indirect calorimetry. Indirect calorimetry was performed using Quark RMR (COSMED, Rome, Italy) on Day 0, 29 and 43 during the HEGC procedure for four 30-minute sessions at time points -570 min to -540 min (baseline), -40 min to -10 min (end of blood glucose adjustment phase), 210 min to 240 min (end of SS1), 450 min to 480 min (end of SS2)., Up to Day 43|Energy expenditure (indirect calorimetry) parameters Carbohydrate/glucose oxidation rate (c) at ss1 and ss2, Carbohydrate/glucose oxidation rate was reported using indirect calorimetry. Indirect calorimetry was performed using Quark RMR (COSMED, Rome, Italy) on Day 0, 29 and 43 during the HEGC procedure for four 30-minute sessions at time points -570 min to -540 min (baseline), -40 min to -10 min (end of blood glucose adjustment phase), 210 min to 240 min (end of SS1), 450 min to 480 min (end of SS2)., Up to Week 43|Energy expenditure (indirect calorimetry) parameters- Fat oxidation rate (f) at ss1 and ss2, Fat oxidation rate was reported using indirect calorimetry. Indirect calorimetry was performed using Quark RMR (COSMED, Rome, Italy) on Day 0, 29 and 43 during the HEGC procedure for four 30-minute sessions at time points -570 min to -540 min (baseline), -40 min to -10 min (end of blood glucose adjustment phase), 210 min to 240 min (end of SS1), 450 min to 480 min (end of SS2)., up to Day 43|Energy expenditure (indirect calorimetry) parameters-Urinary urea excretion rate (n), Urinary urea excretion rate was reported using indirect calorimetry. Indirect calorimetry was performed using Quark RMR (COSMED, Rome, Italy) on Day 0, 29 and 43 during the HEGC procedure for four 30-minute sessions at time points -570 min to -540 min (baseline), -40 min to -10 min (end of blood glucose adjustment phase), 210 min to 240 min (end of SS1), 450 min to 480 min (end of SS2)., Up to Day 43|Energy expenditure (indirect calorimetry) parameters-Oxidative and non- oxidative glucose disposal (VO2 and VCO2) at ss1 and ss2, Oxidative and non- oxidative glucose disposal was reported using indirect calorimetry. Indirect calorimetry was performed using Quark RMR (COSMED, Rome, Italy) on Day 0, 29 and 43 during the HEGC procedure for four 30-minute sessions at time points -570 min to -540 min (baseline), -40 min to -10 min (end of blood glucose adjustment phase), 210 min to 240 min (end of SS1), 450 min to 480 min (end of SS2)., Up to Day 43|Energy expenditure (indirect calorimetry )parameters-Respiratory exchange ratio (RER), RER was defined as the ratio between the amount of O2 consumed and CO2 produced in one breath. The parameter was assessed during indirect measure of heat production (calorimetry)., Up to Day 43|Mean 7-point-blood glucose-AUC, AUC was presented using a 7-point blood glucose profile was performed during the inpatient portion of the study (Day -1, 28 and 42) to measure and record glucose levels throughout the day. Blood glucose concentrations were determined with a glucose analyzer. The first sample was collected early in the morning before the OGTT and standardized meal., Up to Day 42|Muscle histology and biomarkers of oxidative capacity -mitochondrial deoxyribonucleic acid (DNA)., Muscle biopsies were obtained pre-dose (Day -1) and at end of the dosing period (Day 28), Up to Day 28|Muscle histology and biomarkers of oxidative capacity-Citrase synthase activity (Complex I), Muscle biopsies were obtained pre-dose (Day -1) and at end of the dosing period (Day 28) Data for mean and standard deviation was presented., Up to Days 28|Muscle histology and biomarkers of oxidative capacity-Citrase synthase activity (Complex II/III and IV), Muscle biopsies were obtained pre-dose (Day -1) and at end of the dosing period (Day 28) Data for mean and standard deviation was presented., Up to Day 28|Muscle histology and biomarkers of oxidative capacity-succinate dehydrogenase content Complex I, Complex II/III, complex IV., Muscle biopsies were obtained pre-dose (Day -1) and at end of the dosing period (Day 28) Data for mean and standard deviation was presented., Day 0, 29, and 43
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