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

NCT00937326 | Completed Phase 2 Results

• 1 other identifier: 113160
• Study Type: interventional
• Target: 227
• Locations: 8 countries
• Sites: 61

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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (30)

• 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

  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.

  Up to Follow-up (58 days)

• Number of Participants With AE by Intensity of Mild, Moderate and Severe

  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.

  Up to Follow-up (58 days)

• Mean Change From Baseline in Weight Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time

  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.

  Baseline (Day 1, pre-dose) and up to Day 35

• Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time

  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.

  Baseline (Day 1, pre-dose) and up to Day 35

• Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time

  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.

  Baseline (Day 1, pre-dose) and up to Day 35

• Change From Baseline in Vital Sign Parameter of Temperature Over Time

  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.

  Baseline (Day 1, pre-dose) and up to Day 35

• Change From Baseline in Electrocardiogram (ECG) Values Over Time

  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.

  Baseline (Day 1, pre-dose) and up to Day 35

• Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Hematology Parameter of Red Blood Cell (RBC) Count Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Hematology Parameter of Hematocrit Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Hematology Parameter of Hemoglobin Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Concentration Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Hematology Parameter of Mean Corpuscular Volume Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Coagulation Parameters of Activated Partial Thromplastin Time (aPTT) and Prothrombin Time (PT) Over Time

  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.

  Baseline (Day 1), Day 28 and Day 35

• Change From Baseline in Coagulation Parameter of International Normalized Ratio Over Time

  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.

  Baseline (Day 1), Day 28 and Day 35

• Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Chemistry Parameter of Lipid Profile Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Urinalysis Parameter of Specific Gravity Over Time

  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.

  Baseline (Day 1) and up to Day 35

• Change From Baseline in Urinalysis Parameter of pH Over Time

  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.

  Baseline (Day 1) and up to Day 35

• 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

  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.

  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)

• Observed Maximum Plasma Concentration (Cmax) of SRT2104 at Day 1 and Day 28

  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.

  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)

• Time to Cmax (Tmax) at Day 1 and Day 28

  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.

  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)

• Terminal Elimination Half Life (T1/2) of SRT2104 at Day 1 and Day 28

  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.

  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)

• Apparent Total Clearance of SRT2104 From Plasma After Oral Administration (CL/F) on Day 1 and Day 28

  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.

  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)

• Apparent Volume of Distribution After Oral Administration (Vd/F) at Day 1 and Day 28

  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.

  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)

Secondary Outcomes (15)

• Mean Fasting Plasma Glucose (FPG) Levels Over Time

  Up to Day 35

• Change From Baseline in FPG Levels Over Time

  Baseline (Day 1) and up to Day 35

• Mean Fasting Plasma Insulin (FPI) Levels Over Time

  Up to Day 35

• Change From Baseline in FPI Over Time

  Baseline (Day 1) and up to Day 35

• Mean Post-prandial Glucose (PPG) and Post-prandial Insulin (PPI) Levels at Day 28

  Day 28

Study Arms (5)

Placebo

PLACEBO COMPARATOR

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

Arm1 - 0.25g

ACTIVE COMPARATOR

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; Drug: Placebo

Arm2 - 0.5g

ACTIVE COMPARATOR

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; Drug: Placebo

Arm3 - 1g

ACTIVE COMPARATOR

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; Drug: Placebo

Arm4 - 2g

ACTIVE COMPARATOR

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

Interventions

SRT2104 DRUG

SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.

Arm1 - 0.25g; Arm2 - 0.5g; Arm3 - 1g; Arm4 - 2g

Placebo DRUG

Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.

Arm1 - 0.25g; Arm2 - 0.5g; Arm3 - 1g; Placebo

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects of any race and gender within the age range of 30 to 70 years.
• 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
• 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.
• Willingness to provide written informed consent to participate in the study
• HbA1c ≥ 7.5 and ≤ 10.5
• Fasting glucose ≥ 160 and ≤ 240 mg/dL
• Body Mass Index (BMI) ≥ 25.0 kg/m\^2 and ≤ 40.0 kg/m\^2
• On stable metformin medication for at least 3 months (≥ 1.0 g/day) prior to Screening
• No prior history of HIV 1 or 2
• Absence of disease markers for hepatitis B \& C virus
• 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
• Have a normal 12-lead ECG or one with abnormality considered to be clinically insignificant
• Have a normal chest X-ray (P. A. View) or one with abnormality considered to be clinically insignificant
• Comprehension of the nature and purpose of the study and compliance with the requirement of the entire protocol

You may not qualify if:

• Any major illness in the past three months or any significant ongoing chronic medical illness not related to diabetes
• 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.
• History of or current gastro-intestinal diseases influencing drug absorption, except for appendectomy
• History, within 3 years, of drug abuse (including Benzodiazepines, opioids, amphetamine, cocaine, and THC)
• 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 \[one drink is equal to one unit of alcohol (one glass wine, half pint beer, one measure of spirit)\]
• Participation in any clinical trial within the past three months
• History of difficulty in donating blood or accessibility of veins in left or right arm
• Donation of blood (one unit or 350 ml) within three months prior to receiving the first dose of test material
• 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
• Use of any alternate anti-diabetic therapy, except metformin, within three months of enrollment

Sponsors & Collaborators

• Sirtris, a GSK Company: lead
• GlaxoSmithKline: collaborator

Study Sites (61)

GSK Investigational Site

Byala, 7100, Bulgaria

Location

GSK Investigational Site

Dimitrovgrad, 6400, Bulgaria

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GSK Investigational Site

Haskovo, 6300, Bulgaria

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GSK Investigational Site

Pleven, 5800, Bulgaria

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GSK Investigational Site

Plovdiv, 4000, Bulgaria

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GSK Investigational Site

Plovdiv, 4002, Bulgaria

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GSK Investigational Site

Rousse, 7002, Bulgaria

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GSK Investigational Site

Sofia, 1407, Bulgaria

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GSK Investigational Site

Sofia, 1431, Bulgaria

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GSK Investigational Site

Tallinn, 10138, Estonia

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GSK Investigational Site

Tallinn, 10617, Estonia

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GSK Investigational Site

Tallinn, 13419, Estonia

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GSK Investigational Site

Balantonfured, 8230, Hungary

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GSK Investigational Site

Eger, 3300, Hungary

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GSK Investigational Site

Gyula, 5701, Hungary

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GSK Investigational Site

Kecskemét, 6000, Hungary

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GSK Investigational Site

Sopron, 9400, Hungary

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GSK Investigational Site

Szekszárd, 7100, Hungary

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GSK Investigational Site

Zalaegerszeg, 8900, Hungary

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GSK Investigational Site

Cieszyn, 43-400, Poland

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GSK Investigational Site

Lubin, 20-090, Poland

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GSK Investigational Site

Lubin, 59-301, Poland

Location

GSK Investigational Site

Puławy, 24-100, Poland

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GSK Investigational Site

Radzymin, 05-250, Poland

Location

GSK Investigational Site

Ruda Śląska, 41-709, Poland

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GSK Investigational Site

Słupsk, 76-200, Poland

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GSK Investigational Site

Tychy, 43-100, Poland

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GSK Investigational Site

Warsaw, 04-141, Poland

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GSK Investigational Site

Bacau, 600114, Romania

Location

GSK Investigational Site

Brăila, 810249, Romania

Location

GSK Investigational Site

Buzău, 120257, Romania

Location

GSK Investigational Site

Constanța, 900591, Romania

Location

GSK Investigational Site

Oradea, 410169, Romania

Location

GSK Investigational Site

Ploieşti, 100097, Romania

Location

GSK Investigational Site

Timișoara, 300456, Romania

Location

GSK Investigational Site

Barnaul, 656024, Russia

Location

GSK Investigational Site

Kemerovo, 650061, Russia

Location

GSK Investigational Site

Kemerovo, 650099, Russia

Location

GSK Investigational Site

Moscow, 115 280, Russia

Location

GSK Investigational Site

Moscow, 119881, Russia

Location

GSK Investigational Site

Moscow, 121069, Russia

Location

GSK Investigational Site

Moscow, 127486, Russia

Location

GSK Investigational Site

Moscow, 129110, Russia

Location

GSK Investigational Site

Novosibirsk, 630068, Russia

Location

GSK Investigational Site

Novosibirsk, 630090, Russia

Location

GSK Investigational Site

Rostov-on-Don, 344022, Russia

Location

GSK Investigational Site

Saint Petersburg, 190103, Russia

Location

GSK Investigational Site

Saint Petersburg, 194354, Russia

Location

GSK Investigational Site

Tyumen, 625023, Russia

Location

GSK Investigational Site

Ufa, 450071, Russia

Location

GSK Investigational Site

Yaroslavl, 150062, Russia

Location

GSK Investigational Site

Kharkiv, 61022, Ukraine

Location

GSK Investigational Site

Mykolaiv, 54003, Ukraine

Location

GSK Investigational Site

Simferopol, 95017, Ukraine

Location

GSK Investigational Site

Ternopil, 46001, Ukraine

Location

GSK Investigational Site

Vinnitsa, 21010, Ukraine

Location

GSK Investigational Site

Zaporizhzhya, 69001, Ukraine

Location

GSK Investigational Site

Zaporizhzhya, 69035, Ukraine

Location

GSK Investigational Site

Birmingham, B9 5SS, United Kingdom

Location

GSK Investigational Site

London, SE 1 9RT, United Kingdom

Location

GSK Investigational Site

Newport, PO30 5TG, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

SRT2104

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 13, 2009
• Study Start: August 19, 2009
• Primary Completion: September 18, 2010
• Study Completion: September 18, 2010
• Last Updated: July 13, 2018
• Results First Posted: April 9, 2018

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

BU (9); UA (7); ES (3); HU (7); GB (3); PL (9); RU (16); RO (7)