Trial Outcomes & Findings for Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Type 2 Diabetic Human Subjects (NCT NCT00937326)
NCT ID: NCT00937326
Last Updated: 2018-07-13
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
227 participants
Primary outcome timeframe
Up to Follow-up (58 days)
Results posted on
2018-07-13
Participant Flow
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.
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.
Participant milestones
| Measure |
Placebo
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.
|
SRT2104 0.25 g/Day
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.
|
SRT2104 0.5 g/Day
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.
|
SRT2104 1.0 g/Day
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.
|
SRT2104 2.0 g/Day
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.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
46
|
45
|
46
|
45
|
45
|
|
Overall Study
COMPLETED
|
43
|
38
|
42
|
40
|
40
|
|
Overall Study
NOT COMPLETED
|
3
|
7
|
4
|
5
|
5
|
Reasons for withdrawal
| Measure |
Placebo
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.
|
SRT2104 0.25 g/Day
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.
|
SRT2104 0.5 g/Day
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.
|
SRT2104 1.0 g/Day
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.
|
SRT2104 2.0 g/Day
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.
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
3
|
1
|
1
|
2
|
|
Overall Study
Death
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
3
|
4
|
1
|
4
|
3
|
|
Overall Study
Chest X-ray showed a suspicious shadow
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Type 2 Diabetic Human Subjects
Baseline characteristics by cohort
| Measure |
Placebo
n=46 Participants
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.
|
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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
n=227 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
55.8 Years
STANDARD_DEVIATION 8.40 • n=5 Participants
|
58.2 Years
STANDARD_DEVIATION 8.04 • n=7 Participants
|
57.7 Years
STANDARD_DEVIATION 9.00 • n=5 Participants
|
57.3 Years
STANDARD_DEVIATION 8.95 • n=4 Participants
|
55.9 Years
STANDARD_DEVIATION 9.03 • n=21 Participants
|
57.0 Years
STANDARD_DEVIATION 8.67 • n=10 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
126 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
101 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
45 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
44 Participants
n=21 Participants
|
225 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Up to Follow-up (58 days)Population: Safety Analysis Set (SAF) Population was defined as all participants who received at least one dose of any test material during the study.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
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
Any AE related to study medication
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
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
Any AE leading to discontinuation
|
3 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
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
Any fatal AE of death
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
Any AE
|
15 Participants
|
19 Participants
|
11 Participants
|
15 Participants
|
11 Participants
|
|
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
Any SAE
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Follow-up (58 days)Population: Safety Analysis Set Population.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants With AE by Intensity of Mild, Moderate and Severe
Mild AE
|
10 Participants
|
11 Participants
|
8 Participants
|
9 Participants
|
8 Participants
|
|
Number of Participants With AE by Intensity of Mild, Moderate and Severe
Moderate AE
|
6 Participants
|
12 Participants
|
5 Participants
|
7 Participants
|
7 Participants
|
|
Number of Participants With AE by Intensity of Mild, Moderate and Severe
Severe AE
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline in Weight Over Time
Day 28
|
-0.81 Kilogram (kg)
Standard Deviation 2.21
|
-1.25 Kilogram (kg)
Standard Deviation 2.06
|
-0.56 Kilogram (kg)
Standard Deviation 1.68
|
-1.54 Kilogram (kg)
Standard Deviation 3.82
|
-0.17 Kilogram (kg)
Standard Deviation 1.25
|
|
Mean Change From Baseline in Weight Over Time
Day 35
|
-0.91 Kilogram (kg)
Standard Deviation 2.90
|
-1.32 Kilogram (kg)
Standard Deviation 1.89
|
-0.86 Kilogram (kg)
Standard Deviation 1.78
|
-2.74 Kilogram (kg)
Standard Deviation 7.27
|
-0.40 Kilogram (kg)
Standard Deviation 1.39
|
PRIMARY outcome
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 8, 5 minutes
|
-1.65 Millimeter of mercury (mmHg)
Standard Deviation 6.94
|
-0.98 Millimeter of mercury (mmHg)
Standard Deviation 7.06
|
-0.24 Millimeter of mercury (mmHg)
Standard Deviation 5.72
|
-2.38 Millimeter of mercury (mmHg)
Standard Deviation 4.86
|
-2.45 Millimeter of mercury (mmHg)
Standard Deviation 9.16
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 8, 30 minutes
|
-1.93 Millimeter of mercury (mmHg)
Standard Deviation 6.43
|
-1.71 Millimeter of mercury (mmHg)
Standard Deviation 7.10
|
-0.70 Millimeter of mercury (mmHg)
Standard Deviation 5.89
|
-2.58 Millimeter of mercury (mmHg)
Standard Deviation 4.68
|
-2.36 Millimeter of mercury (mmHg)
Standard Deviation 7.19
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 8, 1 hour
|
-0.93 Millimeter of mercury (mmHg)
Standard Deviation 6.54
|
-1.61 Millimeter of mercury (mmHg)
Standard Deviation 7.42
|
-1.63 Millimeter of mercury (mmHg)
Standard Deviation 6.95
|
-2.16 Millimeter of mercury (mmHg)
Standard Deviation 5.54
|
-2.03 Millimeter of mercury (mmHg)
Standard Deviation 7.15
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 15, pre-dose
|
-0.10 Millimeter of mercury (mmHg)
Standard Deviation 7.49
|
-1.21 Millimeter of mercury (mmHg)
Standard Deviation 6.46
|
-0.90 Millimeter of mercury (mmHg)
Standard Deviation 6.81
|
-0.63 Millimeter of mercury (mmHg)
Standard Deviation 6.74
|
-2.30 Millimeter of mercury (mmHg)
Standard Deviation 8.17
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 15, 5 minutes
|
-0.60 Millimeter of mercury (mmHg)
Standard Deviation 8.26
|
-0.98 Millimeter of mercury (mmHg)
Standard Deviation 8.15
|
-1.85 Millimeter of mercury (mmHg)
Standard Deviation 6.57
|
-1.33 Millimeter of mercury (mmHg)
Standard Deviation 7.03
|
-2.70 Millimeter of mercury (mmHg)
Standard Deviation 8.54
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 15, 30 minutes
|
-0.05 Millimeter of mercury (mmHg)
Standard Deviation 7.15
|
-2.15 Millimeter of mercury (mmHg)
Standard Deviation 7.73
|
-2.39 Millimeter of mercury (mmHg)
Standard Deviation 8.22
|
-2.37 Millimeter of mercury (mmHg)
Standard Deviation 6.26
|
-3.33 Millimeter of mercury (mmHg)
Standard Deviation 7.98
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 15, 1 hour
|
0.92 Millimeter of mercury (mmHg)
Standard Deviation 7.57
|
-2.23 Millimeter of mercury (mmHg)
Standard Deviation 7.04
|
-2.07 Millimeter of mercury (mmHg)
Standard Deviation 7.31
|
-2.24 Millimeter of mercury (mmHg)
Standard Deviation 5.51
|
-3.26 Millimeter of mercury (mmHg)
Standard Deviation 5.95
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 22, pre-dose
|
-1.90 Millimeter of mercury (mmHg)
Standard Deviation 6.53
|
-0.67 Millimeter of mercury (mmHg)
Standard Deviation 6.63
|
0.63 Millimeter of mercury (mmHg)
Standard Deviation 8.86
|
-0.44 Millimeter of mercury (mmHg)
Standard Deviation 8.08
|
-1.21 Millimeter of mercury (mmHg)
Standard Deviation 6.90
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 22, 5 minutes
|
-1.62 Millimeter of mercury (mmHg)
Standard Deviation 6.27
|
-1.67 Millimeter of mercury (mmHg)
Standard Deviation 8.62
|
-0.90 Millimeter of mercury (mmHg)
Standard Deviation 8.44
|
-2.54 Millimeter of mercury (mmHg)
Standard Deviation 7.70
|
-3.05 Millimeter of mercury (mmHg)
Standard Deviation 8.91
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 22, 30 minutes
|
-2.53 Millimeter of mercury (mmHg)
Standard Deviation 6.60
|
-1.51 Millimeter of mercury (mmHg)
Standard Deviation 7.44
|
-0.98 Millimeter of mercury (mmHg)
Standard Deviation 8.78
|
-1.30 Millimeter of mercury (mmHg)
Standard Deviation 6.45
|
-2.51 Millimeter of mercury (mmHg)
Standard Deviation 7.91
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 22, 1 hour
|
-1.36 Millimeter of mercury (mmHg)
Standard Deviation 6.41
|
-1.31 Millimeter of mercury (mmHg)
Standard Deviation 7.16
|
-1.35 Millimeter of mercury (mmHg)
Standard Deviation 8.05
|
-2.89 Millimeter of mercury (mmHg)
Standard Deviation 6.67
|
-2.89 Millimeter of mercury (mmHg)
Standard Deviation 6.88
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 27
|
-1.00 Millimeter of mercury (mmHg)
Standard Deviation 7.53
|
-1.43 Millimeter of mercury (mmHg)
Standard Deviation 6.32
|
-0.75 Millimeter of mercury (mmHg)
Standard Deviation 6.53
|
-2.69 Millimeter of mercury (mmHg)
Standard Deviation 6.22
|
-2.86 Millimeter of mercury (mmHg)
Standard Deviation 7.04
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, pre-dose
|
0.14 Millimeter of mercury (mmHg)
Standard Deviation 5.71
|
-1.31 Millimeter of mercury (mmHg)
Standard Deviation 6.66
|
0.25 Millimeter of mercury (mmHg)
Standard Deviation 8.23
|
-1.28 Millimeter of mercury (mmHg)
Standard Deviation 6.30
|
-3.67 Millimeter of mercury (mmHg)
Standard Deviation 6.62
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, 15 minutes
|
-1.24 Millimeter of mercury (mmHg)
Standard Deviation 9.26
|
-1.19 Millimeter of mercury (mmHg)
Standard Deviation 5.58
|
-0.63 Millimeter of mercury (mmHg)
Standard Deviation 8.20
|
-1.28 Millimeter of mercury (mmHg)
Standard Deviation 6.84
|
-4.37 Millimeter of mercury (mmHg)
Standard Deviation 7.42
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, 30 minutes
|
-0.81 Millimeter of mercury (mmHg)
Standard Deviation 7.23
|
-1.57 Millimeter of mercury (mmHg)
Standard Deviation 6.01
|
-1.05 Millimeter of mercury (mmHg)
Standard Deviation 8.90
|
-2.41 Millimeter of mercury (mmHg)
Standard Deviation 6.83
|
-4.37 Millimeter of mercury (mmHg)
Standard Deviation 7.25
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, 1 hour
|
-2.00 Millimeter of mercury (mmHg)
Standard Deviation 6.94
|
-1.07 Millimeter of mercury (mmHg)
Standard Deviation 7.63
|
-1.45 Millimeter of mercury (mmHg)
Standard Deviation 7.37
|
-3.62 Millimeter of mercury (mmHg)
Standard Deviation 5.98
|
-3.58 Millimeter of mercury (mmHg)
Standard Deviation 7.11
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, 2 hour
|
-2.41 Millimeter of mercury (mmHg)
Standard Deviation 5.89
|
-0.93 Millimeter of mercury (mmHg)
Standard Deviation 6.69
|
-2.13 Millimeter of mercury (mmHg)
Standard Deviation 7.57
|
-2.62 Millimeter of mercury (mmHg)
Standard Deviation 5.42
|
-4.14 Millimeter of mercury (mmHg)
Standard Deviation 8.05
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, 3 hour
|
-2.70 Millimeter of mercury (mmHg)
Standard Deviation 7.08
|
-2.71 Millimeter of mercury (mmHg)
Standard Deviation 5.26
|
-2.15 Millimeter of mercury (mmHg)
Standard Deviation 7.83
|
-1.90 Millimeter of mercury (mmHg)
Standard Deviation 6.18
|
-3.31 Millimeter of mercury (mmHg)
Standard Deviation 7.58
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, 4 hour
|
-1.57 Millimeter of mercury (mmHg)
Standard Deviation 5.51
|
-2.64 Millimeter of mercury (mmHg)
Standard Deviation 5.92
|
-2.10 Millimeter of mercury (mmHg)
Standard Deviation 7.73
|
-2.23 Millimeter of mercury (mmHg)
Standard Deviation 5.44
|
-3.30 Millimeter of mercury (mmHg)
Standard Deviation 7.23
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, 8 hour
|
-1.03 Millimeter of mercury (mmHg)
Standard Deviation 5.91
|
-1.57 Millimeter of mercury (mmHg)
Standard Deviation 6.91
|
-1.10 Millimeter of mercury (mmHg)
Standard Deviation 7.73
|
-1.33 Millimeter of mercury (mmHg)
Standard Deviation 6.32
|
-3.02 Millimeter of mercury (mmHg)
Standard Deviation 7.16
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, 12 hour
|
-1.82 Millimeter of mercury (mmHg)
Standard Deviation 6.56
|
-1.93 Millimeter of mercury (mmHg)
Standard Deviation 5.85
|
-0.90 Millimeter of mercury (mmHg)
Standard Deviation 8.45
|
-0.97 Millimeter of mercury (mmHg)
Standard Deviation 6.97
|
-3.58 Millimeter of mercury (mmHg)
Standard Deviation 6.27
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 28, 24 hour
|
-0.71 Millimeter of mercury (mmHg)
Standard Deviation 7.23
|
-2.38 Millimeter of mercury (mmHg)
Standard Deviation 5.41
|
-1.35 Millimeter of mercury (mmHg)
Standard Deviation 8.34
|
-2.21 Millimeter of mercury (mmHg)
Standard Deviation 6.83
|
-3.40 Millimeter of mercury (mmHg)
Standard Deviation 8.66
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 35
|
-0.69 Millimeter of mercury (mmHg)
Standard Deviation 6.38
|
-2.33 Millimeter of mercury (mmHg)
Standard Deviation 8.06
|
0.61 Millimeter of mercury (mmHg)
Standard Deviation 7.29
|
-1.46 Millimeter of mercury (mmHg)
Standard Deviation 7.02
|
-2.07 Millimeter of mercury (mmHg)
Standard Deviation 9.11
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 1, 15 minutes
|
1.30 Millimeter of mercury (mmHg)
Standard Deviation 8.36
|
0.36 Millimeter of mercury (mmHg)
Standard Deviation 5.27
|
-0.88 Millimeter of mercury (mmHg)
Standard Deviation 5.13
|
-0.24 Millimeter of mercury (mmHg)
Standard Deviation 5.45
|
-1.49 Millimeter of mercury (mmHg)
Standard Deviation 9.45
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 1, 30 minutes
|
0.02 Millimeter of mercury (mmHg)
Standard Deviation 6.24
|
1.36 Millimeter of mercury (mmHg)
Standard Deviation 5.59
|
-0.95 Millimeter of mercury (mmHg)
Standard Deviation 6.05
|
-1.10 Millimeter of mercury (mmHg)
Standard Deviation 6.80
|
-1.44 Millimeter of mercury (mmHg)
Standard Deviation 7.16
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 1, 1 hour
|
-0.81 Millimeter of mercury (mmHg)
Standard Deviation 6.78
|
-0.02 Millimeter of mercury (mmHg)
Standard Deviation 6.33
|
-1.83 Millimeter of mercury (mmHg)
Standard Deviation 5.68
|
-1.40 Millimeter of mercury (mmHg)
Standard Deviation 7.11
|
-2.51 Millimeter of mercury (mmHg)
Standard Deviation 10.03
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 1, 2 hour
|
-0.51 Millimeter of mercury (mmHg)
Standard Deviation 5.51
|
-1.45 Millimeter of mercury (mmHg)
Standard Deviation 7.30
|
-1.64 Millimeter of mercury (mmHg)
Standard Deviation 7.51
|
-2.93 Millimeter of mercury (mmHg)
Standard Deviation 7.77
|
-1.60 Millimeter of mercury (mmHg)
Standard Deviation 10.25
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 1, 3 hour
|
-1.14 Millimeter of mercury (mmHg)
Standard Deviation 5.58
|
-1.98 Millimeter of mercury (mmHg)
Standard Deviation 7.22
|
-1.33 Millimeter of mercury (mmHg)
Standard Deviation 6.61
|
-2.71 Millimeter of mercury (mmHg)
Standard Deviation 7.61
|
-2.33 Millimeter of mercury (mmHg)
Standard Deviation 10.78
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 1, 4 hour
|
-1.53 Millimeter of mercury (mmHg)
Standard Deviation 6.52
|
-0.86 Millimeter of mercury (mmHg)
Standard Deviation 7.33
|
-3.71 Millimeter of mercury (mmHg)
Standard Deviation 8.71
|
-2.74 Millimeter of mercury (mmHg)
Standard Deviation 8.16
|
-3.51 Millimeter of mercury (mmHg)
Standard Deviation 11.38
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 1, 8 hour
|
-0.93 Millimeter of mercury (mmHg)
Standard Deviation 7.06
|
0.39 Millimeter of mercury (mmHg)
Standard Deviation 6.96
|
-2.26 Millimeter of mercury (mmHg)
Standard Deviation 8.50
|
-1.45 Millimeter of mercury (mmHg)
Standard Deviation 7.23
|
-4.07 Millimeter of mercury (mmHg)
Standard Deviation 9.19
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 1, 12 hour
|
0.02 Millimeter of mercury (mmHg)
Standard Deviation 7.63
|
0.02 Millimeter of mercury (mmHg)
Standard Deviation 7.78
|
-0.83 Millimeter of mercury (mmHg)
Standard Deviation 8.30
|
0.81 Millimeter of mercury (mmHg)
Standard Deviation 8.03
|
-3.02 Millimeter of mercury (mmHg)
Standard Deviation 12.64
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 1, 24 hour
|
0.14 Millimeter of mercury (mmHg)
Standard Deviation 4.75
|
-0.44 Millimeter of mercury (mmHg)
Standard Deviation 5.68
|
-0.02 Millimeter of mercury (mmHg)
Standard Deviation 5.26
|
-1.39 Millimeter of mercury (mmHg)
Standard Deviation 6.21
|
-1.41 Millimeter of mercury (mmHg)
Standard Deviation 6.11
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 2, pre-dose
|
-0.30 Millimeter of mercury (mmHg)
Standard Deviation 6.49
|
-1.05 Millimeter of mercury (mmHg)
Standard Deviation 6.85
|
-0.31 Millimeter of mercury (mmHg)
Standard Deviation 6.79
|
-2.50 Millimeter of mercury (mmHg)
Standard Deviation 7.70
|
-1.64 Millimeter of mercury (mmHg)
Standard Deviation 8.49
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 2, 5 minutes
|
-0.47 Millimeter of mercury (mmHg)
Standard Deviation 7.07
|
-0.54 Millimeter of mercury (mmHg)
Standard Deviation 5.78
|
-0.40 Millimeter of mercury (mmHg)
Standard Deviation 6.67
|
-1.45 Millimeter of mercury (mmHg)
Standard Deviation 8.00
|
-2.81 Millimeter of mercury (mmHg)
Standard Deviation 9.74
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 2, 5 minutes
|
-0.81 Millimeter of mercury (mmHg)
Standard Deviation 5.67
|
-0.68 Millimeter of mercury (mmHg)
Standard Deviation 6.46
|
-0.88 Millimeter of mercury (mmHg)
Standard Deviation 7.27
|
-2.62 Millimeter of mercury (mmHg)
Standard Deviation 5.79
|
-1.62 Millimeter of mercury (mmHg)
Standard Deviation 7.05
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 2, 30 minutes
|
-0.45 Millimeter of mercury (mmHg)
Standard Deviation 6.74
|
-1.79 Millimeter of mercury (mmHg)
Standard Deviation 6.99
|
-1.80 Millimeter of mercury (mmHg)
Standard Deviation 6.99
|
-2.45 Millimeter of mercury (mmHg)
Standard Deviation 5.60
|
-1.71 Millimeter of mercury (mmHg)
Standard Deviation 6.37
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 2, 1 hour
|
-0.18 Millimeter of mercury (mmHg)
Standard Deviation 6.95
|
-1.68 Millimeter of mercury (mmHg)
Standard Deviation 6.87
|
-1.10 Millimeter of mercury (mmHg)
Standard Deviation 6.84
|
-1.80 Millimeter of mercury (mmHg)
Standard Deviation 6.51
|
-1.65 Millimeter of mercury (mmHg)
Standard Deviation 7.20
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 8, pre-dose
|
-1.30 Millimeter of mercury (mmHg)
Standard Deviation 6.65
|
-0.88 Millimeter of mercury (mmHg)
Standard Deviation 7.49
|
0.02 Millimeter of mercury (mmHg)
Standard Deviation 6.80
|
-2.05 Millimeter of mercury (mmHg)
Standard Deviation 6.18
|
-1.50 Millimeter of mercury (mmHg)
Standard Deviation 8.09
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 2, 30 minutes
|
-0.43 Millimeter of mercury (mmHg)
Standard Deviation 6.81
|
-1.47 Millimeter of mercury (mmHg)
Standard Deviation 5.99
|
-2.00 Millimeter of mercury (mmHg)
Standard Deviation 6.88
|
-1.38 Millimeter of mercury (mmHg)
Standard Deviation 6.88
|
-3.13 Millimeter of mercury (mmHg)
Standard Deviation 8.79
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 2, 1 hour
|
-0.48 Millimeter of mercury (mmHg)
Standard Deviation 6.24
|
-1.34 Millimeter of mercury (mmHg)
Standard Deviation 7.33
|
-1.32 Millimeter of mercury (mmHg)
Standard Deviation 7.67
|
-0.88 Millimeter of mercury (mmHg)
Standard Deviation 7.38
|
-3.22 Millimeter of mercury (mmHg)
Standard Deviation 8.67
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 8, pre-dose
|
-1.63 Millimeter of mercury (mmHg)
Standard Deviation 6.22
|
0.42 Millimeter of mercury (mmHg)
Standard Deviation 10.22
|
0.68 Millimeter of mercury (mmHg)
Standard Deviation 9.93
|
-1.36 Millimeter of mercury (mmHg)
Standard Deviation 8.57
|
-2.83 Millimeter of mercury (mmHg)
Standard Deviation 10.96
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 8, 5 minutes
|
-1.47 Millimeter of mercury (mmHg)
Standard Deviation 5.50
|
1.00 Millimeter of mercury (mmHg)
Standard Deviation 7.76
|
1.20 Millimeter of mercury (mmHg)
Standard Deviation 9.63
|
-0.73 Millimeter of mercury (mmHg)
Standard Deviation 7.93
|
-3.67 Millimeter of mercury (mmHg)
Standard Deviation 10.94
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 8, 30 minutes
|
-0.85 Millimeter of mercury (mmHg)
Standard Deviation 6.48
|
-0.29 Millimeter of mercury (mmHg)
Standard Deviation 7.82
|
0.33 Millimeter of mercury (mmHg)
Standard Deviation 9.31
|
-1.92 Millimeter of mercury (mmHg)
Standard Deviation 8.31
|
-1.72 Millimeter of mercury (mmHg)
Standard Deviation 9.10
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 8, 1 hour
|
-1.00 Millimeter of mercury (mmHg)
Standard Deviation 5.68
|
-1.71 Millimeter of mercury (mmHg)
Standard Deviation 7.80
|
-2.75 Millimeter of mercury (mmHg)
Standard Deviation 10.30
|
-1.87 Millimeter of mercury (mmHg)
Standard Deviation 7.66
|
-2.24 Millimeter of mercury (mmHg)
Standard Deviation 10.22
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 15, pre-dose
|
-0.43 Millimeter of mercury (mmHg)
Standard Deviation 7.22
|
0.65 Millimeter of mercury (mmHg)
Standard Deviation 8.22
|
0.76 Millimeter of mercury (mmHg)
Standard Deviation 9.66
|
0.03 Millimeter of mercury (mmHg)
Standard Deviation 8.50
|
-2.77 Millimeter of mercury (mmHg)
Standard Deviation 10.88
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 15, 5 minutes
|
-1.15 Millimeter of mercury (mmHg)
Standard Deviation 6.47
|
0.69 Millimeter of mercury (mmHg)
Standard Deviation 8.67
|
-0.27 Millimeter of mercury (mmHg)
Standard Deviation 7.89
|
-1.18 Millimeter of mercury (mmHg)
Standard Deviation 8.75
|
-4.16 Millimeter of mercury (mmHg)
Standard Deviation 12.17
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 15, 30 minutes
|
-0.61 Millimeter of mercury (mmHg)
Standard Deviation 8.31
|
0.03 Millimeter of mercury (mmHg)
Standard Deviation 8.98
|
-1.83 Millimeter of mercury (mmHg)
Standard Deviation 9.16
|
-1.97 Millimeter of mercury (mmHg)
Standard Deviation 8.36
|
-3.56 Millimeter of mercury (mmHg)
Standard Deviation 10.28
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 15, 1 hour
|
-0.24 Millimeter of mercury (mmHg)
Standard Deviation 6.43
|
-0.54 Millimeter of mercury (mmHg)
Standard Deviation 7.27
|
-0.98 Millimeter of mercury (mmHg)
Standard Deviation 9.96
|
-1.50 Millimeter of mercury (mmHg)
Standard Deviation 7.91
|
-3.50 Millimeter of mercury (mmHg)
Standard Deviation 10.25
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 22, pre-dose
|
-0.67 Millimeter of mercury (mmHg)
Standard Deviation 8.49
|
-0.53 Millimeter of mercury (mmHg)
Standard Deviation 8.71
|
-0.08 Millimeter of mercury (mmHg)
Standard Deviation 9.92
|
0.08 Millimeter of mercury (mmHg)
Standard Deviation 10.59
|
-2.07 Millimeter of mercury (mmHg)
Standard Deviation 9.75
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 22, 5 minutes
|
-1.46 Millimeter of mercury (mmHg)
Standard Deviation 6.87
|
-0.57 Millimeter of mercury (mmHg)
Standard Deviation 6.72
|
0.08 Millimeter of mercury (mmHg)
Standard Deviation 9.18
|
-1.18 Millimeter of mercury (mmHg)
Standard Deviation 9.91
|
-3.77 Millimeter of mercury (mmHg)
Standard Deviation 11.97
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 22, 30 minutes
|
-1.56 Millimeter of mercury (mmHg)
Standard Deviation 6.64
|
-1.77 Millimeter of mercury (mmHg)
Standard Deviation 6.69
|
-1.10 Millimeter of mercury (mmHg)
Standard Deviation 9.78
|
-2.05 Millimeter of mercury (mmHg)
Standard Deviation 8.73
|
-3.03 Millimeter of mercury (mmHg)
Standard Deviation 10.05
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 22, 1 hour
|
-1.64 Millimeter of mercury (mmHg)
Standard Deviation 6.68
|
-1.51 Millimeter of mercury (mmHg)
Standard Deviation 8.29
|
-0.85 Millimeter of mercury (mmHg)
Standard Deviation 9.57
|
-2.24 Millimeter of mercury (mmHg)
Standard Deviation 9.37
|
-3.39 Millimeter of mercury (mmHg)
Standard Deviation 9.31
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 27
|
-0.49 Millimeter of mercury (mmHg)
Standard Deviation 7.74
|
-0.48 Millimeter of mercury (mmHg)
Standard Deviation 8.68
|
0.15 Millimeter of mercury (mmHg)
Standard Deviation 9.04
|
-1.05 Millimeter of mercury (mmHg)
Standard Deviation 8.69
|
-2.91 Millimeter of mercury (mmHg)
Standard Deviation 9.87
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, pre-dose
|
-0.05 Millimeter of mercury (mmHg)
Standard Deviation 7.17
|
-1.10 Millimeter of mercury (mmHg)
Standard Deviation 9.35
|
0.70 Millimeter of mercury (mmHg)
Standard Deviation 9.92
|
-0.90 Millimeter of mercury (mmHg)
Standard Deviation 8.04
|
-2.60 Millimeter of mercury (mmHg)
Standard Deviation 10.39
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, 15 minutes
|
-1.86 Millimeter of mercury (mmHg)
Standard Deviation 7.11
|
-1.21 Millimeter of mercury (mmHg)
Standard Deviation 9.99
|
-0.63 Millimeter of mercury (mmHg)
Standard Deviation 9.60
|
-1.56 Millimeter of mercury (mmHg)
Standard Deviation 8.34
|
-4.58 Millimeter of mercury (mmHg)
Standard Deviation 11.88
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, 30 minutes
|
-2.65 Millimeter of mercury (mmHg)
Standard Deviation 6.47
|
-1.69 Millimeter of mercury (mmHg)
Standard Deviation 9.70
|
-1.43 Millimeter of mercury (mmHg)
Standard Deviation 9.09
|
-2.44 Millimeter of mercury (mmHg)
Standard Deviation 8.02
|
-4.07 Millimeter of mercury (mmHg)
Standard Deviation 11.26
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, 1 hour
|
-2.78 Millimeter of mercury (mmHg)
Standard Deviation 6.77
|
-1.26 Millimeter of mercury (mmHg)
Standard Deviation 8.40
|
-2.13 Millimeter of mercury (mmHg)
Standard Deviation 9.24
|
-3.85 Millimeter of mercury (mmHg)
Standard Deviation 7.35
|
-4.74 Millimeter of mercury (mmHg)
Standard Deviation 11.62
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, 2 hour
|
-2.65 Millimeter of mercury (mmHg)
Standard Deviation 6.63
|
-0.98 Millimeter of mercury (mmHg)
Standard Deviation 9.10
|
-2.90 Millimeter of mercury (mmHg)
Standard Deviation 7.32
|
-3.21 Millimeter of mercury (mmHg)
Standard Deviation 8.70
|
-5.07 Millimeter of mercury (mmHg)
Standard Deviation 12.33
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, 3 hour
|
-2.84 Millimeter of mercury (mmHg)
Standard Deviation 6.24
|
-2.60 Millimeter of mercury (mmHg)
Standard Deviation 8.32
|
-2.03 Millimeter of mercury (mmHg)
Standard Deviation 8.98
|
-1.79 Millimeter of mercury (mmHg)
Standard Deviation 9.01
|
-4.33 Millimeter of mercury (mmHg)
Standard Deviation 11.33
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, 4 hour
|
-3.16 Millimeter of mercury (mmHg)
Standard Deviation 6.86
|
-2.21 Millimeter of mercury (mmHg)
Standard Deviation 7.89
|
-3.48 Millimeter of mercury (mmHg)
Standard Deviation 9.35
|
-2.21 Millimeter of mercury (mmHg)
Standard Deviation 7.56
|
-4.28 Millimeter of mercury (mmHg)
Standard Deviation 11.36
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, 8 hour
|
-2.11 Millimeter of mercury (mmHg)
Standard Deviation 7.12
|
-1.45 Millimeter of mercury (mmHg)
Standard Deviation 8.96
|
-2.83 Millimeter of mercury (mmHg)
Standard Deviation 9.35
|
-1.85 Millimeter of mercury (mmHg)
Standard Deviation 9.02
|
-4.51 Millimeter of mercury (mmHg)
Standard Deviation 12.32
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, 12 hour
|
-0.97 Millimeter of mercury (mmHg)
Standard Deviation 6.73
|
-2.14 Millimeter of mercury (mmHg)
Standard Deviation 8.08
|
-0.75 Millimeter of mercury (mmHg)
Standard Deviation 8.48
|
-0.82 Millimeter of mercury (mmHg)
Standard Deviation 9.52
|
-4.95 Millimeter of mercury (mmHg)
Standard Deviation 11.61
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 28, 24 hour
|
-1.42 Millimeter of mercury (mmHg)
Standard Deviation 6.82
|
-1.45 Millimeter of mercury (mmHg)
Standard Deviation 7.42
|
-0.08 Millimeter of mercury (mmHg)
Standard Deviation 8.02
|
-3.00 Millimeter of mercury (mmHg)
Standard Deviation 8.28
|
-4.05 Millimeter of mercury (mmHg)
Standard Deviation 11.72
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
SBP, Day 35
|
-2.83 Millimeter of mercury (mmHg)
Standard Deviation 7.47
|
-0.70 Millimeter of mercury (mmHg)
Standard Deviation 8.05
|
0.37 Millimeter of mercury (mmHg)
Standard Deviation 8.66
|
-0.51 Millimeter of mercury (mmHg)
Standard Deviation 9.88
|
-4.44 Millimeter of mercury (mmHg)
Standard Deviation 12.39
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 1, 15 minutes
|
-0.42 Millimeter of mercury (mmHg)
Standard Deviation 5.13
|
-1.41 Millimeter of mercury (mmHg)
Standard Deviation 6.44
|
-0.38 Millimeter of mercury (mmHg)
Standard Deviation 5.96
|
-1.55 Millimeter of mercury (mmHg)
Standard Deviation 5.67
|
-1.12 Millimeter of mercury (mmHg)
Standard Deviation 6.71
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 1, 30 minutes
|
-1.05 Millimeter of mercury (mmHg)
Standard Deviation 4.35
|
-1.73 Millimeter of mercury (mmHg)
Standard Deviation 5.87
|
-0.29 Millimeter of mercury (mmHg)
Standard Deviation 5.75
|
-1.88 Millimeter of mercury (mmHg)
Standard Deviation 5.87
|
-1.37 Millimeter of mercury (mmHg)
Standard Deviation 5.98
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 1, 1 hour
|
-1.09 Millimeter of mercury (mmHg)
Standard Deviation 5.12
|
-1.89 Millimeter of mercury (mmHg)
Standard Deviation 5.91
|
-0.95 Millimeter of mercury (mmHg)
Standard Deviation 5.64
|
-2.83 Millimeter of mercury (mmHg)
Standard Deviation 5.33
|
-2.70 Millimeter of mercury (mmHg)
Standard Deviation 6.65
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 1, 2 hour
|
-1.26 Millimeter of mercury (mmHg)
Standard Deviation 6.08
|
-1.66 Millimeter of mercury (mmHg)
Standard Deviation 5.69
|
-0.45 Millimeter of mercury (mmHg)
Standard Deviation 5.32
|
-3.55 Millimeter of mercury (mmHg)
Standard Deviation 6.01
|
-0.74 Millimeter of mercury (mmHg)
Standard Deviation 7.50
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 1, 3 hour
|
-1.28 Millimeter of mercury (mmHg)
Standard Deviation 6.03
|
-2.57 Millimeter of mercury (mmHg)
Standard Deviation 5.60
|
-1.81 Millimeter of mercury (mmHg)
Standard Deviation 6.73
|
-1.76 Millimeter of mercury (mmHg)
Standard Deviation 5.13
|
-1.74 Millimeter of mercury (mmHg)
Standard Deviation 6.08
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 1, 4 hour
|
-0.77 Millimeter of mercury (mmHg)
Standard Deviation 6.56
|
-2.00 Millimeter of mercury (mmHg)
Standard Deviation 6.46
|
-0.90 Millimeter of mercury (mmHg)
Standard Deviation 6.81
|
-1.69 Millimeter of mercury (mmHg)
Standard Deviation 5.05
|
-1.86 Millimeter of mercury (mmHg)
Standard Deviation 7.88
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 1, 8 hour
|
-0.56 Millimeter of mercury (mmHg)
Standard Deviation 6.42
|
-0.73 Millimeter of mercury (mmHg)
Standard Deviation 6.23
|
-1.98 Millimeter of mercury (mmHg)
Standard Deviation 6.23
|
-1.52 Millimeter of mercury (mmHg)
Standard Deviation 6.69
|
-2.16 Millimeter of mercury (mmHg)
Standard Deviation 6.91
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 1, 12 hour
|
-0.16 Millimeter of mercury (mmHg)
Standard Deviation 7.16
|
-1.64 Millimeter of mercury (mmHg)
Standard Deviation 7.81
|
-1.24 Millimeter of mercury (mmHg)
Standard Deviation 6.14
|
-0.38 Millimeter of mercury (mmHg)
Standard Deviation 5.78
|
-1.40 Millimeter of mercury (mmHg)
Standard Deviation 8.76
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 1, 24 hour
|
-0.14 Millimeter of mercury (mmHg)
Standard Deviation 6.24
|
-1.14 Millimeter of mercury (mmHg)
Standard Deviation 6.91
|
-0.76 Millimeter of mercury (mmHg)
Standard Deviation 6.84
|
-2.38 Millimeter of mercury (mmHg)
Standard Deviation 6.05
|
-1.14 Millimeter of mercury (mmHg)
Standard Deviation 6.07
|
|
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Over Time
DBP, Day 2, pre-dose
|
-0.28 Millimeter of mercury (mmHg)
Standard Deviation 6.08
|
-1.02 Millimeter of mercury (mmHg)
Standard Deviation 6.93
|
-0.90 Millimeter of mercury (mmHg)
Standard Deviation 7.16
|
-2.33 Millimeter of mercury (mmHg)
Standard Deviation 6.43
|
-1.24 Millimeter of mercury (mmHg)
Standard Deviation 6.23
|
PRIMARY outcome
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 1, 15 minutes
|
1.02 Beats per minute (bpm)
Standard Deviation 5.24
|
0.23 Beats per minute (bpm)
Standard Deviation 5.08
|
1.21 Beats per minute (bpm)
Standard Deviation 6.32
|
1.60 Beats per minute (bpm)
Standard Deviation 4.47
|
-0.02 Beats per minute (bpm)
Standard Deviation 5.82
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 1, 30 minutes
|
1.12 Beats per minute (bpm)
Standard Deviation 5.55
|
0.47 Beats per minute (bpm)
Standard Deviation 6.10
|
1.12 Beats per minute (bpm)
Standard Deviation 6.06
|
0.26 Beats per minute (bpm)
Standard Deviation 5.40
|
0.05 Beats per minute (bpm)
Standard Deviation 5.99
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 1, 1 hour
|
0.33 Beats per minute (bpm)
Standard Deviation 5.84
|
-0.35 Beats per minute (bpm)
Standard Deviation 6.27
|
-0.48 Beats per minute (bpm)
Standard Deviation 7.19
|
0.43 Beats per minute (bpm)
Standard Deviation 4.88
|
0.21 Beats per minute (bpm)
Standard Deviation 6.16
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 1, 2 hour
|
0.09 Beats per minute (bpm)
Standard Deviation 5.95
|
-1.16 Beats per minute (bpm)
Standard Deviation 5.63
|
-1.19 Beats per minute (bpm)
Standard Deviation 5.56
|
0.45 Beats per minute (bpm)
Standard Deviation 5.55
|
-0.23 Beats per minute (bpm)
Standard Deviation 5.63
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 1, 3 hour
|
0.07 Beats per minute (bpm)
Standard Deviation 6.25
|
-1.19 Beats per minute (bpm)
Standard Deviation 6.50
|
0.12 Beats per minute (bpm)
Standard Deviation 6.83
|
0.19 Beats per minute (bpm)
Standard Deviation 5.71
|
-0.12 Beats per minute (bpm)
Standard Deviation 5.39
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 1, 4 hour
|
-0.53 Beats per minute (bpm)
Standard Deviation 6.04
|
-0.40 Beats per minute (bpm)
Standard Deviation 6.81
|
-1.81 Beats per minute (bpm)
Standard Deviation 5.64
|
0.05 Beats per minute (bpm)
Standard Deviation 6.03
|
-1.37 Beats per minute (bpm)
Standard Deviation 5.94
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 1, 8 hour
|
-0.79 Beats per minute (bpm)
Standard Deviation 4.29
|
-0.72 Beats per minute (bpm)
Standard Deviation 5.15
|
-2.14 Beats per minute (bpm)
Standard Deviation 5.26
|
0.95 Beats per minute (bpm)
Standard Deviation 5.71
|
-0.70 Beats per minute (bpm)
Standard Deviation 6.00
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 1, 12 hour
|
-1.05 Beats per minute (bpm)
Standard Deviation 4.77
|
-0.72 Beats per minute (bpm)
Standard Deviation 6.03
|
-1.38 Beats per minute (bpm)
Standard Deviation 5.58
|
0.45 Beats per minute (bpm)
Standard Deviation 6.66
|
-1.05 Beats per minute (bpm)
Standard Deviation 6.35
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 1, 24 hour
|
-0.40 Beats per minute (bpm)
Standard Deviation 5.57
|
0.14 Beats per minute (bpm)
Standard Deviation 5.09
|
-0.19 Beats per minute (bpm)
Standard Deviation 5.06
|
0.64 Beats per minute (bpm)
Standard Deviation 5.78
|
0.12 Beats per minute (bpm)
Standard Deviation 5.49
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 2, pre-dose
|
0.30 Beats per minute (bpm)
Standard Deviation 6.06
|
0.14 Beats per minute (bpm)
Standard Deviation 5.02
|
-0.14 Beats per minute (bpm)
Standard Deviation 4.95
|
0.81 Beats per minute (bpm)
Standard Deviation 5.61
|
0.14 Beats per minute (bpm)
Standard Deviation 6.11
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 2, 5 minutes
|
1.00 Beats per minute (bpm)
Standard Deviation 5.81
|
-0.12 Beats per minute (bpm)
Standard Deviation 5.69
|
0.67 Beats per minute (bpm)
Standard Deviation 5.85
|
1.14 Beats per minute (bpm)
Standard Deviation 5.34
|
1.33 Beats per minute (bpm)
Standard Deviation 5.59
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 2, 30 minutes
|
0.28 Beats per minute (bpm)
Standard Deviation 5.80
|
-0.08 Beats per minute (bpm)
Standard Deviation 6.07
|
-0.76 Beats per minute (bpm)
Standard Deviation 5.61
|
1.03 Beats per minute (bpm)
Standard Deviation 4.70
|
0.47 Beats per minute (bpm)
Standard Deviation 4.97
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 2, 1 hour
|
0.18 Beats per minute (bpm)
Standard Deviation 5.85
|
-1.13 Beats per minute (bpm)
Standard Deviation 6.63
|
-1.29 Beats per minute (bpm)
Standard Deviation 6.30
|
1.35 Beats per minute (bpm)
Standard Deviation 4.92
|
-0.38 Beats per minute (bpm)
Standard Deviation 4.50
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 8, pre-dose
|
-0.84 Beats per minute (bpm)
Standard Deviation 6.74
|
1.53 Beats per minute (bpm)
Standard Deviation 8.69
|
0.15 Beats per minute (bpm)
Standard Deviation 7.80
|
1.36 Beats per minute (bpm)
Standard Deviation 6.47
|
0.79 Beats per minute (bpm)
Standard Deviation 5.72
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 8, 5 minutes
|
-0.56 Beats per minute (bpm)
Standard Deviation 6.47
|
1.12 Beats per minute (bpm)
Standard Deviation 8.94
|
-0.07 Beats per minute (bpm)
Standard Deviation 8.13
|
1.85 Beats per minute (bpm)
Standard Deviation 6.31
|
0.67 Beats per minute (bpm)
Standard Deviation 5.15
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 8, 30 minutes
|
-0.15 Beats per minute (bpm)
Standard Deviation 6.78
|
-1.11 Beats per minute (bpm)
Standard Deviation 7.51
|
0.30 Beats per minute (bpm)
Standard Deviation 8.46
|
1.66 Beats per minute (bpm)
Standard Deviation 5.56
|
0.59 Beats per minute (bpm)
Standard Deviation 5.92
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 8, 1 hour
|
-0.35 Beats per minute (bpm)
Standard Deviation 6.91
|
-1.26 Beats per minute (bpm)
Standard Deviation 6.73
|
-0.93 Beats per minute (bpm)
Standard Deviation 7.45
|
1.71 Beats per minute (bpm)
Standard Deviation 6.23
|
0.47 Beats per minute (bpm)
Standard Deviation 4.99
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 15, pre-dose
|
-0.53 Beats per minute (bpm)
Standard Deviation 8.05
|
0.23 Beats per minute (bpm)
Standard Deviation 6.79
|
-1.10 Beats per minute (bpm)
Standard Deviation 8.42
|
-0.43 Beats per minute (bpm)
Standard Deviation 6.07
|
-0.35 Beats per minute (bpm)
Standard Deviation 7.53
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 15, 5 minutes
|
-0.55 Beats per minute (bpm)
Standard Deviation 8.34
|
0.43 Beats per minute (bpm)
Standard Deviation 8.14
|
-1.17 Beats per minute (bpm)
Standard Deviation 8.44
|
0.68 Beats per minute (bpm)
Standard Deviation 6.36
|
-0.05 Beats per minute (bpm)
Standard Deviation 6.69
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 15, 30 minutes
|
-0.24 Beats per minute (bpm)
Standard Deviation 8.31
|
-0.49 Beats per minute (bpm)
Standard Deviation 8.42
|
-1.68 Beats per minute (bpm)
Standard Deviation 8.30
|
0.82 Beats per minute (bpm)
Standard Deviation 6.08
|
-0.72 Beats per minute (bpm)
Standard Deviation 6.01
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 15, 1 hour
|
-0.81 Beats per minute (bpm)
Standard Deviation 7.50
|
-1.46 Beats per minute (bpm)
Standard Deviation 7.08
|
-0.73 Beats per minute (bpm)
Standard Deviation 8.33
|
0.13 Beats per minute (bpm)
Standard Deviation 5.74
|
-0.16 Beats per minute (bpm)
Standard Deviation 5.25
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 22, pre-dose
|
-1.33 Beats per minute (bpm)
Standard Deviation 8.21
|
1.33 Beats per minute (bpm)
Standard Deviation 7.89
|
-0.50 Beats per minute (bpm)
Standard Deviation 10.19
|
1.13 Beats per minute (bpm)
Standard Deviation 7.45
|
0.44 Beats per minute (bpm)
Standard Deviation 7.10
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 22, 5 minutes
|
-0.59 Beats per minute (bpm)
Standard Deviation 7.27
|
0.88 Beats per minute (bpm)
Standard Deviation 8.50
|
-0.10 Beats per minute (bpm)
Standard Deviation 9.16
|
0.62 Beats per minute (bpm)
Standard Deviation 6.74
|
0.88 Beats per minute (bpm)
Standard Deviation 6.90
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 22, 30 minutes
|
-1.08 Beats per minute (bpm)
Standard Deviation 7.69
|
0.05 Beats per minute (bpm)
Standard Deviation 8.33
|
0.53 Beats per minute (bpm)
Standard Deviation 9.53
|
0.51 Beats per minute (bpm)
Standard Deviation 6.42
|
0.41 Beats per minute (bpm)
Standard Deviation 7.02
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 22, 1 hour
|
-1.03 Beats per minute (bpm)
Standard Deviation 8.11
|
0.46 Beats per minute (bpm)
Standard Deviation 7.45
|
0.28 Beats per minute (bpm)
Standard Deviation 9.25
|
0.03 Beats per minute (bpm)
Standard Deviation 7.02
|
-0.21 Beats per minute (bpm)
Standard Deviation 6.05
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 27
|
-1.19 Beats per minute (bpm)
Standard Deviation 8.27
|
-1.83 Beats per minute (bpm)
Standard Deviation 6.58
|
-0.75 Beats per minute (bpm)
Standard Deviation 8.05
|
-0.10 Beats per minute (bpm)
Standard Deviation 5.91
|
-1.70 Beats per minute (bpm)
Standard Deviation 6.94
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, pre-dose
|
-1.95 Beats per minute (bpm)
Standard Deviation 6.99
|
-1.26 Beats per minute (bpm)
Standard Deviation 5.44
|
-0.73 Beats per minute (bpm)
Standard Deviation 9.60
|
-0.67 Beats per minute (bpm)
Standard Deviation 5.89
|
-1.67 Beats per minute (bpm)
Standard Deviation 6.92
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, 15 minutes
|
-1.11 Beats per minute (bpm)
Standard Deviation 7.44
|
-0.50 Beats per minute (bpm)
Standard Deviation 6.95
|
-0.03 Beats per minute (bpm)
Standard Deviation 10.28
|
0.31 Beats per minute (bpm)
Standard Deviation 5.66
|
-0.67 Beats per minute (bpm)
Standard Deviation 7.61
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, 30 minutes
|
-1.84 Beats per minute (bpm)
Standard Deviation 6.99
|
-0.12 Beats per minute (bpm)
Standard Deviation 7.30
|
-0.43 Beats per minute (bpm)
Standard Deviation 9.47
|
0.26 Beats per minute (bpm)
Standard Deviation 5.73
|
-0.60 Beats per minute (bpm)
Standard Deviation 6.97
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, 1 hour
|
-1.76 Beats per minute (bpm)
Standard Deviation 7.03
|
-1.20 Beats per minute (bpm)
Standard Deviation 6.75
|
-1.18 Beats per minute (bpm)
Standard Deviation 9.58
|
0.69 Beats per minute (bpm)
Standard Deviation 6.55
|
-0.44 Beats per minute (bpm)
Standard Deviation 6.55
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, 2 hour
|
-3.16 Beats per minute (bpm)
Standard Deviation 6.13
|
-1.20 Beats per minute (bpm)
Standard Deviation 6.55
|
-0.65 Beats per minute (bpm)
Standard Deviation 9.23
|
0.21 Beats per minute (bpm)
Standard Deviation 6.88
|
-1.40 Beats per minute (bpm)
Standard Deviation 6.93
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, 3 hour
|
-1.97 Beats per minute (bpm)
Standard Deviation 6.72
|
-1.46 Beats per minute (bpm)
Standard Deviation 7.41
|
-1.53 Beats per minute (bpm)
Standard Deviation 8.71
|
0.36 Beats per minute (bpm)
Standard Deviation 7.15
|
-0.55 Beats per minute (bpm)
Standard Deviation 6.56
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, 4 hour
|
-2.22 Beats per minute (bpm)
Standard Deviation 6.94
|
-1.24 Beats per minute (bpm)
Standard Deviation 6.40
|
-1.93 Beats per minute (bpm)
Standard Deviation 9.45
|
0.67 Beats per minute (bpm)
Standard Deviation 7.19
|
-0.91 Beats per minute (bpm)
Standard Deviation 7.33
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, 8 hour
|
-2.14 Beats per minute (bpm)
Standard Deviation 6.29
|
-1.10 Beats per minute (bpm)
Standard Deviation 6.87
|
-1.63 Beats per minute (bpm)
Standard Deviation 7.88
|
0.05 Beats per minute (bpm)
Standard Deviation 7.42
|
-0.40 Beats per minute (bpm)
Standard Deviation 7.47
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, 12 hour
|
-2.05 Beats per minute (bpm)
Standard Deviation 6.15
|
-2.02 Beats per minute (bpm)
Standard Deviation 7.82
|
-0.20 Beats per minute (bpm)
Standard Deviation 8.29
|
0.54 Beats per minute (bpm)
Standard Deviation 7.57
|
-1.72 Beats per minute (bpm)
Standard Deviation 7.00
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 28, 24 hour
|
-1.50 Beats per minute (bpm)
Standard Deviation 7.26
|
-0.60 Beats per minute (bpm)
Standard Deviation 5.49
|
-1.33 Beats per minute (bpm)
Standard Deviation 7.91
|
-0.92 Beats per minute (bpm)
Standard Deviation 6.59
|
-1.58 Beats per minute (bpm)
Standard Deviation 7.43
|
|
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) Over Time
Day 35
|
-1.90 Beats per minute (bpm)
Standard Deviation 6.80
|
-0.56 Beats per minute (bpm)
Standard Deviation 6.62
|
-3.15 Beats per minute (bpm)
Standard Deviation 8.33
|
0.56 Beats per minute (bpm)
Standard Deviation 5.96
|
-0.30 Beats per minute (bpm)
Standard Deviation 7.20
|
PRIMARY outcome
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 1, 15 minutes
|
-0.07 Breaths per minute
Standard Deviation 1.12
|
-0.16 Breaths per minute
Standard Deviation 1.15
|
0.33 Breaths per minute
Standard Deviation 0.79
|
0.00 Breaths per minute
Standard Deviation 0.99
|
0.14 Breaths per minute
Standard Deviation 0.89
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 1, 30 minutes
|
0.05 Breaths per minute
Standard Deviation 1.11
|
0.19 Breaths per minute
Standard Deviation 0.96
|
0.96 Breaths per minute
Standard Deviation 1.11
|
-0.02 Breaths per minute
Standard Deviation 1.14
|
0.07 Breaths per minute
Standard Deviation 1.10
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 1, 1 hour
|
-0.12 Breaths per minute
Standard Deviation 0.96
|
-0.23 Breaths per minute
Standard Deviation 1.09
|
0.10 Breaths per minute
Standard Deviation 1.08
|
0.07 Breaths per minute
Standard Deviation 0.97
|
0.09 Breaths per minute
Standard Deviation 0.97
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 1, 2 hour
|
0.19 Breaths per minute
Standard Deviation 1.14
|
-0.37 Breaths per minute
Standard Deviation 1.11
|
0.10 Breaths per minute
Standard Deviation 1.05
|
0.21 Breaths per minute
Standard Deviation 1.07
|
-0.26 Breaths per minute
Standard Deviation 0.93
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 1, 3 hour
|
0.02 Breaths per minute
Standard Deviation 1.01
|
-0.42 Breaths per minute
Standard Deviation 1.10
|
0.31 Breaths per minute
Standard Deviation 1.09
|
0.17 Breaths per minute
Standard Deviation 1.26
|
-0.02 Breaths per minute
Standard Deviation 0.94
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 1, 4 hour
|
-0.07 Breaths per minute
Standard Deviation 1.01
|
-0.12 Breaths per minute
Standard Deviation 1.12
|
-0.02 Breaths per minute
Standard Deviation 1.18
|
0.07 Breaths per minute
Standard Deviation 1.11
|
-0.05 Breaths per minute
Standard Deviation 1.09
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 1, 8 hour
|
-0.02 Breaths per minute
Standard Deviation 0.99
|
-0.26 Breaths per minute
Standard Deviation 1.27
|
0.19 Breaths per minute
Standard Deviation 1.09
|
0.07 Breaths per minute
Standard Deviation 0.89
|
0.02 Breaths per minute
Standard Deviation 1.20
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 1, 12 hour
|
-0.05 Breaths per minute
Standard Deviation 0.97
|
-0.16 Breaths per minute
Standard Deviation 0.92
|
0.24 Breaths per minute
Standard Deviation 1.05
|
0.31 Breaths per minute
Standard Deviation 1.07
|
-0.14 Breaths per minute
Standard Deviation 1.06
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 1, 24 hour
|
0.09 Breaths per minute
Standard Deviation 1.25
|
-0.45 Breaths per minute
Standard Deviation 0.90
|
-0.05 Breaths per minute
Standard Deviation 0.76
|
0.00 Breaths per minute
Standard Deviation 0.83
|
-0.16 Breaths per minute
Standard Deviation 1.00
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 2, pre-dose
|
0.09 Breaths per minute
Standard Deviation 1.17
|
-0.40 Breaths per minute
Standard Deviation 0.90
|
-0.02 Breaths per minute
Standard Deviation 0.78
|
0.00 Breaths per minute
Standard Deviation 0.83
|
0.00 Breaths per minute
Standard Deviation 0.99
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 2, 5 minutes
|
0.02 Breaths per minute
Standard Deviation 0.94
|
-0.32 Breaths per minute
Standard Deviation 1.01
|
0.10 Breaths per minute
Standard Deviation 1.01
|
-0.02 Breaths per minute
Standard Deviation 0.92
|
0.29 Breaths per minute
Standard Deviation 0.89
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 2, 30 minutes
|
0.10 Breaths per minute
Standard Deviation 1.10
|
-0.21 Breaths per minute
Standard Deviation 0.93
|
-0.15 Breaths per minute
Standard Deviation 1.22
|
-0.05 Breaths per minute
Standard Deviation 1.06
|
0.18 Breaths per minute
Standard Deviation 1.01
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 2, 1 hour
|
0.13 Breaths per minute
Standard Deviation 1.09
|
-0.39 Breaths per minute
Standard Deviation 0.97
|
0.00 Breaths per minute
Standard Deviation 0.74
|
0.10 Breaths per minute
Standard Deviation 0.90
|
0.11 Breaths per minute
Standard Deviation 0.97
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 8, pre-dose
|
0.00 Breaths per minute
Standard Deviation 1.00
|
-0.37 Breaths per minute
Standard Deviation 1.18
|
0.24 Breaths per minute
Standard Deviation 0.99
|
-0.21 Breaths per minute
Standard Deviation 0.95
|
0.02 Breaths per minute
Standard Deviation 1.33
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 8, 5 minutes
|
0.09 Breaths per minute
Standard Deviation 1.00
|
-0.43 Breaths per minute
Standard Deviation 1.43
|
0.24 Breaths per minute
Standard Deviation 1.11
|
-0.08 Breaths per minute
Standard Deviation 1.07
|
-0.05 Breaths per minute
Standard Deviation 1.08
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 8, 30 minutes
|
0.05 Breaths per minute
Standard Deviation 1.32
|
-0.50 Breaths per minute
Standard Deviation 1.25
|
0.35 Breaths per minute
Standard Deviation 1.00
|
-0.08 Breaths per minute
Standard Deviation 0.97
|
0.03 Breaths per minute
Standard Deviation 1.04
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 8, 1 hour
|
0.00 Breaths per minute
Standard Deviation 1.06
|
-0.37 Breaths per minute
Standard Deviation 1.15
|
0.08 Breaths per minute
Standard Deviation 1.10
|
0.11 Breaths per minute
Standard Deviation 0.98
|
0.05 Breaths per minute
Standard Deviation 1.11
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 15, pre-dose
|
-0.05 Breaths per minute
Standard Deviation 1.06
|
-0.58 Breaths per minute
Standard Deviation 1.12
|
0.17 Breaths per minute
Standard Deviation 1.09
|
0.00 Breaths per minute
Standard Deviation 0.99
|
0.09 Breaths per minute
Standard Deviation 1.15
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 15, 5 minutes
|
-0.15 Breaths per minute
Standard Deviation 1.33
|
-0.45 Breaths per minute
Standard Deviation 1.37
|
0.07 Breaths per minute
Standard Deviation 1.10
|
-0.08 Breaths per minute
Standard Deviation 1.12
|
-0.02 Breaths per minute
Standard Deviation 1.24
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 15, 30 minutes
|
-0.08 Breaths per minute
Standard Deviation 1.02
|
-0.28 Breaths per minute
Standard Deviation 1.30
|
0.17 Breaths per minute
Standard Deviation 1.32
|
0.03 Breaths per minute
Standard Deviation 1.03
|
0.05 Breaths per minute
Standard Deviation 1.15
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 15, 1 hour
|
0.00 Breaths per minute
Standard Deviation 1.37
|
-0.64 Breaths per minute
Standard Deviation 1.18
|
0.10 Breaths per minute
Standard Deviation 1.07
|
-0.11 Breaths per minute
Standard Deviation 1.01
|
0.16 Breaths per minute
Standard Deviation 1.08
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 22, pre-dose
|
-0.05 Breaths per minute
Standard Deviation 1.05
|
-0.51 Breaths per minute
Standard Deviation 1.18
|
0.10 Breaths per minute
Standard Deviation 1.10
|
0.13 Breaths per minute
Standard Deviation 1.03
|
-0.02 Breaths per minute
Standard Deviation 1.22
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 22, 5 minutes
|
0.08 Breaths per minute
Standard Deviation 1.20
|
-0.62 Breaths per minute
Standard Deviation 1.45
|
0.25 Breaths per minute
Standard Deviation 1.19
|
0.13 Breaths per minute
Standard Deviation 1.00
|
0.07 Breaths per minute
Standard Deviation 1.10
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 22, 30 minutes
|
-0.14 Breaths per minute
Standard Deviation 1.29
|
-0.51 Breaths per minute
Standard Deviation 1.00
|
0.20 Breaths per minute
Standard Deviation 1.16
|
0.03 Breaths per minute
Standard Deviation 1.07
|
0.10 Breaths per minute
Standard Deviation 1.25
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 22, 1 hour
|
0.11 Breaths per minute
Standard Deviation 1.09
|
-0.41 Breaths per minute
Standard Deviation 1.04
|
0.38 Breaths per minute
Standard Deviation 1.17
|
0.00 Breaths per minute
Standard Deviation 1.25
|
0.13 Breaths per minute
Standard Deviation 1.19
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 27
|
0.11 Breaths per minute
Standard Deviation 0.97
|
-0.67 Breaths per minute
Standard Deviation 1.14
|
0.00 Breaths per minute
Standard Deviation 1.28
|
0.26 Breaths per minute
Standard Deviation 1.16
|
-0.14 Breaths per minute
Standard Deviation 1.06
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, pre-dose
|
0.19 Breaths per minute
Standard Deviation 1.05
|
-0.71 Breaths per minute
Standard Deviation 1.20
|
0.10 Breaths per minute
Standard Deviation 1.26
|
0.03 Breaths per minute
Standard Deviation 0.78
|
-0.09 Breaths per minute
Standard Deviation 1.17
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, 15 minutes
|
-0.08 Breaths per minute
Standard Deviation 1.06
|
-0.56 Breaths per minute
Standard Deviation 1.12
|
0.30 Breaths per minute
Standard Deviation 1.36
|
-0.05 Breaths per minute
Standard Deviation 1.02
|
-0.33 Breaths per minute
Standard Deviation 1.23
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, 30 minutes
|
0.08 Breaths per minute
Standard Deviation 1.23
|
-0.32 Breaths per minute
Standard Deviation 1.19
|
0.10 Breaths per minute
Standard Deviation 1.52
|
-0.03 Breaths per minute
Standard Deviation 1.04
|
-0.21 Breaths per minute
Standard Deviation 1.06
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, 1 hour
|
-0.08 Breaths per minute
Standard Deviation 1.16
|
-0.37 Breaths per minute
Standard Deviation 0.99
|
0.23 Breaths per minute
Standard Deviation 1.54
|
-0.05 Breaths per minute
Standard Deviation 1.23
|
-0.19 Breaths per minute
Standard Deviation 1.30
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, 2 hour
|
-0.24 Breaths per minute
Standard Deviation 1.04
|
-0.68 Breaths per minute
Standard Deviation 1.21
|
0.30 Breaths per minute
Standard Deviation 1.40
|
-0.10 Breaths per minute
Standard Deviation 0.97
|
-0.33 Breaths per minute
Standard Deviation 1.19
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, 3 hour
|
0.00 Breaths per minute
Standard Deviation 1.31
|
-0.56 Breaths per minute
Standard Deviation 1.16
|
0.10 Breaths per minute
Standard Deviation 1.37
|
-0.13 Breaths per minute
Standard Deviation 1.08
|
-0.07 Breaths per minute
Standard Deviation 1.30
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, 4 hour
|
0.05 Breaths per minute
Standard Deviation 1.08
|
-0.46 Breaths per minute
Standard Deviation 1.14
|
0.25 Breaths per minute
Standard Deviation 1.53
|
0.05 Breaths per minute
Standard Deviation 1.36
|
-0.05 Breaths per minute
Standard Deviation 1.27
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, 8 hour
|
0.14 Breaths per minute
Standard Deviation 1.00
|
-0.54 Breaths per minute
Standard Deviation 0.98
|
0.23 Breaths per minute
Standard Deviation 1.29
|
-0.08 Breaths per minute
Standard Deviation 1.18
|
-0.33 Breaths per minute
Standard Deviation 1.43
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, 12 hour
|
0.05 Breaths per minute
Standard Deviation 1.18
|
-0.49 Breaths per minute
Standard Deviation 1.14
|
0.20 Breaths per minute
Standard Deviation 1.11
|
0.03 Breaths per minute
Standard Deviation 1.25
|
-0.35 Breaths per minute
Standard Deviation 1.34
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 28, 24 hour
|
-0.03 Breaths per minute
Standard Deviation 0.91
|
-0.64 Breaths per minute
Standard Deviation 1.10
|
0.13 Breaths per minute
Standard Deviation 1.45
|
-0.18 Breaths per minute
Standard Deviation 1.02
|
-0.19 Breaths per minute
Standard Deviation 1.19
|
|
Change From Baseline in Vital Sign Parameter of Respiratory Rate (RR) Over Time
Day 35
|
0.05 Breaths per minute
Standard Deviation 1.01
|
-0.56 Breaths per minute
Standard Deviation 1.10
|
0.07 Breaths per minute
Standard Deviation 1.47
|
0.02 Breaths per minute
Standard Deviation 0.88
|
-0.35 Breaths per minute
Standard Deviation 1.34
|
PRIMARY outcome
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 22, pre-dose
|
0.04 Degree celcius
Standard Deviation 0.25
|
-0.02 Degree celcius
Standard Deviation 0.13
|
-0.01 Degree celcius
Standard Deviation 0.25
|
0.01 Degree celcius
Standard Deviation 0.10
|
0.00 Degree celcius
Standard Deviation 0.20
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 1, 15 minutes
|
-0.00 Degree celcius
Standard Deviation 0.14
|
0.01 Degree celcius
Standard Deviation 0.11
|
0.04 Degree celcius
Standard Deviation 0.13
|
0.01 Degree celcius
Standard Deviation 0.26
|
0.03 Degree celcius
Standard Deviation 0.12
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 1, 30 minutes
|
-0.01 Degree celcius
Standard Deviation 0.12
|
-0.00 Degree celcius
Standard Deviation 0.13
|
0.04 Degree celcius
Standard Deviation 0.12
|
0.03 Degree celcius
Standard Deviation 0.20
|
0.04 Degree celcius
Standard Deviation 0.21
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 1, 1 hour
|
-0.00 Degree celcius
Standard Deviation 0.16
|
0.00 Degree celcius
Standard Deviation 0.13
|
0.04 Degree celcius
Standard Deviation 0.10
|
0.03 Degree celcius
Standard Deviation 0.26
|
0.05 Degree celcius
Standard Deviation 0.18
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 1, 2 hour
|
0.01 Degree celcius
Standard Deviation 0.20
|
0.02 Degree celcius
Standard Deviation 0.14
|
0.06 Degree celcius
Standard Deviation 0.15
|
0.05 Degree celcius
Standard Deviation 0.21
|
0.02 Degree celcius
Standard Deviation 0.19
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 1, 3 hour
|
-0.00 Degree celcius
Standard Deviation 0.18
|
-0.03 Degree celcius
Standard Deviation 0.14
|
0.06 Degree celcius
Standard Deviation 0.16
|
0.01 Degree celcius
Standard Deviation 0.20
|
0.05 Degree celcius
Standard Deviation 0.20
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 1, 4 hour
|
0.02 Degree celcius
Standard Deviation 0.18
|
0.02 Degree celcius
Standard Deviation 0.18
|
0.05 Degree celcius
Standard Deviation 0.15
|
0.03 Degree celcius
Standard Deviation 0.26
|
0.05 Degree celcius
Standard Deviation 0.17
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 1, 8 hour
|
0.03 Degree celcius
Standard Deviation 0.20
|
0.03 Degree celcius
Standard Deviation 0.14
|
0.05 Degree celcius
Standard Deviation 0.14
|
0.02 Degree celcius
Standard Deviation 0.20
|
0.07 Degree celcius
Standard Deviation 0.23
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 1, 12 hour
|
0.01 Degree celcius
Standard Deviation 0.17
|
0.03 Degree celcius
Standard Deviation 0.18
|
0.05 Degree celcius
Standard Deviation 0.15
|
0.06 Degree celcius
Standard Deviation 0.23
|
0.12 Degree celcius
Standard Deviation 0.24
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 1, 24 hour
|
-0.03 Degree celcius
Standard Deviation 0.23
|
0.01 Degree celcius
Standard Deviation 0.18
|
0.01 Degree celcius
Standard Deviation 0.19
|
0.00 Degree celcius
Standard Deviation 0.23
|
0.03 Degree celcius
Standard Deviation 0.16
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 2, pre-dose
|
-0.03 Degree celcius
Standard Deviation 0.23
|
0.02 Degree celcius
Standard Deviation 0.18
|
0.01 Degree celcius
Standard Deviation 0.19
|
0.01 Degree celcius
Standard Deviation 0.23
|
0.02 Degree celcius
Standard Deviation 0.15
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 2, 5 minutes
|
-0.00 Degree celcius
Standard Deviation 0.18
|
0.01 Degree celcius
Standard Deviation 0.16
|
-0.03 Degree celcius
Standard Deviation 0.16
|
0.05 Degree celcius
Standard Deviation 0.21
|
0.02 Degree celcius
Standard Deviation 0.18
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 2, 30 minutes
|
-0.00 Degree celcius
Standard Deviation 0.15
|
-0.01 Degree celcius
Standard Deviation 0.14
|
0.02 Degree celcius
Standard Deviation 0.17
|
0.06 Degree celcius
Standard Deviation 0.22
|
0.05 Degree celcius
Standard Deviation 0.13
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 2, 1 hour
|
-0.00 Degree celcius
Standard Deviation 0.16
|
-0.00 Degree celcius
Standard Deviation 0.16
|
0.03 Degree celcius
Standard Deviation 0.14
|
0.04 Degree celcius
Standard Deviation 0.23
|
0.04 Degree celcius
Standard Deviation 0.11
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 8, pre-dose
|
0.03 Degree celcius
Standard Deviation 0.17
|
0.00 Degree celcius
Standard Deviation 0.24
|
0.02 Degree celcius
Standard Deviation 0.18
|
-0.01 Degree celcius
Standard Deviation 0.22
|
0.07 Degree celcius
Standard Deviation 0.25
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 8, 5 minutes
|
0.03 Degree celcius
Standard Deviation 0.18
|
0.01 Degree celcius
Standard Deviation 0.19
|
0.01 Degree celcius
Standard Deviation 0.17
|
0.03 Degree celcius
Standard Deviation 0.21
|
0.05 Degree celcius
Standard Deviation 0.21
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 8, 30 minutes
|
0.00 Degree celcius
Standard Deviation 0.16
|
-0.03 Degree celcius
Standard Deviation 0.19
|
0.03 Degree celcius
Standard Deviation 0.17
|
0.04 Degree celcius
Standard Deviation 0.20
|
0.06 Degree celcius
Standard Deviation 0.20
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 8, 1 hour
|
0.01 Degree celcius
Standard Deviation 0.16
|
-0.02 Degree celcius
Standard Deviation 0.21
|
0.03 Degree celcius
Standard Deviation 0.20
|
0.03 Degree celcius
Standard Deviation 0.24
|
0.03 Degree celcius
Standard Deviation 0.14
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 15, pre-dose
|
0.00 Degree celcius
Standard Deviation 0.17
|
0.02 Degree celcius
Standard Deviation 0.19
|
0.06 Degree celcius
Standard Deviation 0.21
|
0.01 Degree celcius
Standard Deviation 0.19
|
0.03 Degree celcius
Standard Deviation 0.24
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 15, 5 minutes
|
0.01 Degree celcius
Standard Deviation 0.18
|
0.01 Degree celcius
Standard Deviation 0.20
|
0.05 Degree celcius
Standard Deviation 0.17
|
0.02 Degree celcius
Standard Deviation 0.24
|
0.05 Degree celcius
Standard Deviation 0.20
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 15, 30 minutes
|
-0.01 Degree celcius
Standard Deviation 0.20
|
-0.01 Degree celcius
Standard Deviation 0.18
|
0.05 Degree celcius
Standard Deviation 0.18
|
0.03 Degree celcius
Standard Deviation 0.21
|
0.07 Degree celcius
Standard Deviation 0.20
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 15, 1 hour
|
0.04 Degree celcius
Standard Deviation 0.15
|
-0.02 Degree celcius
Standard Deviation 0.19
|
0.04 Degree celcius
Standard Deviation 0.15
|
0.01 Degree celcius
Standard Deviation 0.15
|
0.05 Degree celcius
Standard Deviation 0.14
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 22, 5 minutes
|
0.04 Degree celcius
Standard Deviation 0.23
|
-0.00 Degree celcius
Standard Deviation 0.16
|
-0.01 Degree celcius
Standard Deviation 0.20
|
0.00 Degree celcius
Standard Deviation 0.12
|
0.01 Degree celcius
Standard Deviation 0.17
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 22, 30 minutes
|
0.04 Degree celcius
Standard Deviation 0.21
|
-0.03 Degree celcius
Standard Deviation 0.12
|
0.03 Degree celcius
Standard Deviation 0.23
|
0.01 Degree celcius
Standard Deviation 0.10
|
0.04 Degree celcius
Standard Deviation 0.16
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 22, 1 hour
|
0.05 Degree celcius
Standard Deviation 0.21
|
0.01 Degree celcius
Standard Deviation 0.14
|
0.02 Degree celcius
Standard Deviation 0.22
|
0.01 Degree celcius
Standard Deviation 0.09
|
0.02 Degree celcius
Standard Deviation 0.17
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 27
|
0.01 Degree celcius
Standard Deviation 0.24
|
0.01 Degree celcius
Standard Deviation 0.20
|
0.05 Degree celcius
Standard Deviation 0.21
|
0.03 Degree celcius
Standard Deviation 0.13
|
0.04 Degree celcius
Standard Deviation 0.21
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, pre-dose
|
-0.00 Degree celcius
Standard Deviation 0.18
|
-0.01 Degree celcius
Standard Deviation 0.19
|
0.00 Degree celcius
Standard Deviation 0.19
|
-0.01 Degree celcius
Standard Deviation 0.18
|
-0.00 Degree celcius
Standard Deviation 0.17
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, 15 minutes
|
-0.00 Degree celcius
Standard Deviation 0.20
|
0.00 Degree celcius
Standard Deviation 0.18
|
0.04 Degree celcius
Standard Deviation 0.21
|
-0.00 Degree celcius
Standard Deviation 0.17
|
0.02 Degree celcius
Standard Deviation 0.17
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, 30 minutes
|
-0.01 Degree celcius
Standard Deviation 0.24
|
-0.01 Degree celcius
Standard Deviation 0.17
|
0.05 Degree celcius
Standard Deviation 0.24
|
0.02 Degree celcius
Standard Deviation 0.17
|
0.02 Degree celcius
Standard Deviation 0.15
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, 1 hour
|
-0.04 Degree celcius
Standard Deviation 0.28
|
-0.01 Degree celcius
Standard Deviation 0.15
|
0.04 Degree celcius
Standard Deviation 0.24
|
0.00 Degree celcius
Standard Deviation 0.12
|
0.02 Degree celcius
Standard Deviation 0.17
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, 2 hour
|
-0.00 Degree celcius
Standard Deviation 0.25
|
-0.04 Degree celcius
Standard Deviation 0.16
|
0.04 Degree celcius
Standard Deviation 0.18
|
0.02 Degree celcius
Standard Deviation 0.13
|
0.03 Degree celcius
Standard Deviation 0.19
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, 3 hour
|
0.01 Degree celcius
Standard Deviation 0.26
|
-0.01 Degree celcius
Standard Deviation 0.21
|
0.02 Degree celcius
Standard Deviation 0.22
|
0.00 Degree celcius
Standard Deviation 0.16
|
0.02 Degree celcius
Standard Deviation 0.13
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, 4 hour
|
0.00 Degree celcius
Standard Deviation 0.27
|
-0.02 Degree celcius
Standard Deviation 0.16
|
0.02 Degree celcius
Standard Deviation 0.22
|
0.01 Degree celcius
Standard Deviation 0.11
|
-0.01 Degree celcius
Standard Deviation 0.25
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, 8 hour
|
0.05 Degree celcius
Standard Deviation 0.24
|
0.00 Degree celcius
Standard Deviation 0.17
|
0.05 Degree celcius
Standard Deviation 0.17
|
0.02 Degree celcius
Standard Deviation 0.16
|
0.05 Degree celcius
Standard Deviation 0.21
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, 12 hour
|
0.06 Degree celcius
Standard Deviation 0.27
|
0.01 Degree celcius
Standard Deviation 0.18
|
0.05 Degree celcius
Standard Deviation 0.21
|
-0.01 Degree celcius
Standard Deviation 0.15
|
0.05 Degree celcius
Standard Deviation 0.16
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 28, 24 hour
|
-0.02 Degree celcius
Standard Deviation 0.25
|
-0.09 Degree celcius
Standard Deviation 0.35
|
0.02 Degree celcius
Standard Deviation 0.26
|
-0.02 Degree celcius
Standard Deviation 0.19
|
-0.01 Degree celcius
Standard Deviation 0.22
|
|
Change From Baseline in Vital Sign Parameter of Temperature Over Time
Day 35
|
0.07 Degree celcius
Standard Deviation 0.18
|
-0.02 Degree celcius
Standard Deviation 0.18
|
0.07 Degree celcius
Standard Deviation 0.23
|
0.02 Degree celcius
Standard Deviation 0.32
|
-0.00 Degree celcius
Standard Deviation 0.24
|
PRIMARY outcome
Timeframe: Baseline (Day 1, pre-dose) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
PR interval, Day 1, post-dose
|
1.47 Millisecond
Standard Deviation 13.07
|
0.58 Millisecond
Standard Deviation 12.43
|
0.32 Millisecond
Standard Deviation 9.96
|
1.57 Millisecond
Standard Deviation 11.91
|
0.12 Millisecond
Standard Deviation 9.92
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
PR interval, Day 8
|
-3.42 Millisecond
Standard Deviation 18.04
|
0.45 Millisecond
Standard Deviation 14.15
|
-2.46 Millisecond
Standard Deviation 14.66
|
-3.63 Millisecond
Standard Deviation 15.56
|
-0.26 Millisecond
Standard Deviation 17.29
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
PR interval, Day 15
|
-3.20 Millisecond
Standard Deviation 16.45
|
-5.10 Millisecond
Standard Deviation 19.64
|
-0.78 Millisecond
Standard Deviation 12.10
|
-1.03 Millisecond
Standard Deviation 12.96
|
-5.79 Millisecond
Standard Deviation 15.29
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
PR interval, Day 22
|
-0.31 Millisecond
Standard Deviation 18.12
|
-1.19 Millisecond
Standard Deviation 14.86
|
0.15 Millisecond
Standard Deviation 12.31
|
-1.46 Millisecond
Standard Deviation 14.71
|
-2.38 Millisecond
Standard Deviation 16.84
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
PR interval, Day 28, pre-dose
|
-3.46 Millisecond
Standard Deviation 18.59
|
-2.39 Millisecond
Standard Deviation 14.43
|
3.70 Millisecond
Standard Deviation 13.45
|
0.31 Millisecond
Standard Deviation 17.74
|
-0.55 Millisecond
Standard Deviation 14.81
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
PR interval, Day 28, post-dose
|
-1.22 Millisecond
Standard Deviation 17.40
|
-1.59 Millisecond
Standard Deviation 16.55
|
1.88 Millisecond
Standard Deviation 15.35
|
3.33 Millisecond
Standard Deviation 13.27
|
-1.98 Millisecond
Standard Deviation 15.72
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
PR interval, Day 35
|
-1.22 Millisecond
Standard Deviation 25.54
|
0.48 Millisecond
Standard Deviation 19.88
|
1.95 Millisecond
Standard Deviation 13.81
|
1.15 Millisecond
Standard Deviation 10.41
|
-0.07 Millisecond
Standard Deviation 16.43
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QRS interval, Day 1, post-dose
|
1.07 Millisecond
Standard Deviation 9.67
|
-0.16 Millisecond
Standard Deviation 3.31
|
0.54 Millisecond
Standard Deviation 7.18
|
1.45 Millisecond
Standard Deviation 8.12
|
-0.83 Millisecond
Standard Deviation 8.31
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QRS interval, Day 8
|
-17.49 Millisecond
Standard Deviation 107.04
|
0.81 Millisecond
Standard Deviation 6.78
|
0.56 Millisecond
Standard Deviation 7.23
|
0.85 Millisecond
Standard Deviation 10.15
|
-0.50 Millisecond
Standard Deviation 7.74
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QRS interval, Day 15
|
-16.15 Millisecond
Standard Deviation 110.73
|
-0.17 Millisecond
Standard Deviation 6.26
|
-1.37 Millisecond
Standard Deviation 11.87
|
0.80 Millisecond
Standard Deviation 8.16
|
-1.05 Millisecond
Standard Deviation 6.89
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QRS interval, Day 22
|
-19.31 Millisecond
Standard Deviation 112.93
|
-0.26 Millisecond
Standard Deviation 7.15
|
-1.00 Millisecond
Standard Deviation 5.43
|
0.28 Millisecond
Standard Deviation 9.51
|
0.14 Millisecond
Standard Deviation 5.88
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QRS interval, Day 28, pre-dose
|
-20.00 Millisecond
Standard Deviation 120.11
|
-0.54 Millisecond
Standard Deviation 6.24
|
-1.28 Millisecond
Standard Deviation 6.80
|
-0.54 Millisecond
Standard Deviation 7.41
|
-0.81 Millisecond
Standard Deviation 9.55
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QRS interval, Day 28, post-dose
|
-19.38 Millisecond
Standard Deviation 120.28
|
-0.85 Millisecond
Standard Deviation 7.62
|
-0.03 Millisecond
Standard Deviation 6.62
|
0.21 Millisecond
Standard Deviation 9.09
|
-0.14 Millisecond
Standard Deviation 11.71
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QRS interval, Day 35
|
-12.39 Millisecond
Standard Deviation 112.59
|
-1.21 Millisecond
Standard Deviation 5.58
|
-1.17 Millisecond
Standard Deviation 10.59
|
0.83 Millisecond
Standard Deviation 8.89
|
-0.36 Millisecond
Standard Deviation 6.55
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QT interval, Day 1, post-dose
|
-2.44 Millisecond
Standard Deviation 20.72
|
1.23 Millisecond
Standard Deviation 18.96
|
3.49 Millisecond
Standard Deviation 18.44
|
1.17 Millisecond
Standard Deviation 17.14
|
-0.29 Millisecond
Standard Deviation 14.09
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QT interval, Day 8
|
-7.56 Millisecond
Standard Deviation 32.44
|
-2.74 Millisecond
Standard Deviation 21.35
|
0.68 Millisecond
Standard Deviation 13.49
|
-2.98 Millisecond
Standard Deviation 25.80
|
-1.17 Millisecond
Standard Deviation 18.65
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QT interval, Day 15
|
0.40 Millisecond
Standard Deviation 21.66
|
-0.66 Millisecond
Standard Deviation 22.63
|
-0.98 Millisecond
Standard Deviation 15.75
|
1.53 Millisecond
Standard Deviation 19.98
|
0.93 Millisecond
Standard Deviation 23.43
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QT interval, Day 22
|
1.31 Millisecond
Standard Deviation 21.31
|
1.36 Millisecond
Standard Deviation 22.41
|
-6.00 Millisecond
Standard Deviation 18.92
|
0.64 Millisecond
Standard Deviation 18.54
|
1.38 Millisecond
Standard Deviation 20.93
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QT interval, Day 28, pre-dose
|
1.62 Millisecond
Standard Deviation 19.05
|
1.46 Millisecond
Standard Deviation 27.63
|
3.48 Millisecond
Standard Deviation 20.88
|
1.00 Millisecond
Standard Deviation 18.20
|
9.17 Millisecond
Standard Deviation 25.76
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QT interval, Day 28, post-dose
|
4.27 Millisecond
Standard Deviation 18.31
|
3.80 Millisecond
Standard Deviation 24.89
|
4.35 Millisecond
Standard Deviation 24.70
|
-1.28 Millisecond
Standard Deviation 24.60
|
0.90 Millisecond
Standard Deviation 34.52
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QT interval, Day 35
|
4.56 Millisecond
Standard Deviation 22.44
|
0.36 Millisecond
Standard Deviation 20.27
|
5.12 Millisecond
Standard Deviation 26.01
|
4.27 Millisecond
Standard Deviation 27.43
|
2.10 Millisecond
Standard Deviation 22.76
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QTc interval, Day 1, post-dose
|
-1.60 Millisecond
Standard Deviation 16.31
|
1.28 Millisecond
Standard Deviation 14.46
|
3.37 Millisecond
Standard Deviation 18.91
|
-1.71 Millisecond
Standard Deviation 23.06
|
-2.52 Millisecond
Standard Deviation 16.05
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QTc interval, Day 8
|
-3.40 Millisecond
Standard Deviation 27.38
|
3.64 Millisecond
Standard Deviation 20.77
|
4.17 Millisecond
Standard Deviation 20.65
|
1.45 Millisecond
Standard Deviation 25.90
|
5.02 Millisecond
Standard Deviation 21.98
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QTc interval, Day 15
|
-3.05 Millisecond
Standard Deviation 26.25
|
2.78 Millisecond
Standard Deviation 15.96
|
0.68 Millisecond
Standard Deviation 19.64
|
4.40 Millisecond
Standard Deviation 23.37
|
-0.57 Millisecond
Standard Deviation 21.03
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QTc interval, Day 22
|
-4.21 Millisecond
Standard Deviation 17.59
|
5.52 Millisecond
Standard Deviation 17.55
|
-4.13 Millisecond
Standard Deviation 23.18
|
-0.10 Millisecond
Standard Deviation 22.32
|
3.21 Millisecond
Standard Deviation 17.87
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QTc interval, Day 28, pre-dose
|
2.35 Millisecond
Standard Deviation 18.90
|
-0.71 Millisecond
Standard Deviation 24.18
|
1.50 Millisecond
Standard Deviation 19.86
|
-4.67 Millisecond
Standard Deviation 19.30
|
4.98 Millisecond
Standard Deviation 17.02
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QTc interval, Day 28, post-dose
|
0.54 Millisecond
Standard Deviation 21.20
|
2.39 Millisecond
Standard Deviation 23.09
|
0.83 Millisecond
Standard Deviation 19.86
|
-4.44 Millisecond
Standard Deviation 20.43
|
2.05 Millisecond
Standard Deviation 21.32
|
|
Change From Baseline in Electrocardiogram (ECG) Values Over Time
QTc interval, Day 35
|
-0.05 Millisecond
Standard Deviation 21.78
|
2.90 Millisecond
Standard Deviation 16.15
|
0.63 Millisecond
Standard Deviation 26.55
|
-1.34 Millisecond
Standard Deviation 28.57
|
2.38 Millisecond
Standard Deviation 19.88
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Eosinophil count, Day 22
|
0.01 Giga cells per liter
Standard Deviation 0.10
|
0.01 Giga cells per liter
Standard Deviation 0.15
|
0.02 Giga cells per liter
Standard Deviation 0.20
|
0.03 Giga cells per liter
Standard Deviation 0.16
|
-0.01 Giga cells per liter
Standard Deviation 0.21
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Eosinophil count, Day 28
|
0.02 Giga cells per liter
Standard Deviation 0.13
|
0.02 Giga cells per liter
Standard Deviation 0.27
|
-0.00 Giga cells per liter
Standard Deviation 0.10
|
0.02 Giga cells per liter
Standard Deviation 0.17
|
-0.05 Giga cells per liter
Standard Deviation 0.11
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Baseophil count, Day 22
|
0.01 Giga cells per liter
Standard Deviation 0.03
|
-0.00 Giga cells per liter
Standard Deviation 0.02
|
-0.00 Giga cells per liter
Standard Deviation 0.02
|
-0.01 Giga cells per liter
Standard Deviation 0.02
|
0.01 Giga cells per liter
Standard Deviation 0.01
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Baseophil count, Day 28
|
0.00 Giga cells per liter
Standard Deviation 0.02
|
0.00 Giga cells per liter
Standard Deviation 0.02
|
-0.00 Giga cells per liter
Standard Deviation 0.02
|
-0.00 Giga cells per liter
Standard Deviation 0.02
|
0.01 Giga cells per liter
Standard Deviation 0.02
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Baseophil count Day 35
|
0.01 Giga cells per liter
Standard Deviation 0.02
|
0.00 Giga cells per liter
Standard Deviation 0.02
|
0.00 Giga cells per liter
Standard Deviation 0.02
|
-0.00 Giga cells per liter
Standard Deviation 0.02
|
0.00 Giga cells per liter
Standard Deviation 0.02
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Eosinophil count, Day 8
|
0.01 Giga cells per liter
Standard Deviation 0.13
|
0.03 Giga cells per liter
Standard Deviation 0.17
|
-0.01 Giga cells per liter
Standard Deviation 0.09
|
0.01 Giga cells per liter
Standard Deviation 0.14
|
0.01 Giga cells per liter
Standard Deviation 0.14
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Eosinophil count, Day 15
|
0.01 Giga cells per liter
Standard Deviation 0.12
|
0.04 Giga cells per liter
Standard Deviation 0.28
|
0.01 Giga cells per liter
Standard Deviation 0.11
|
-0.03 Giga cells per liter
Standard Deviation 0.12
|
-0.04 Giga cells per liter
Standard Deviation 0.13
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Baseophil count, Day 8
|
0.00 Giga cells per liter
Standard Deviation 0.02
|
0.00 Giga cells per liter
Standard Deviation 0.01
|
0.00 Giga cells per liter
Standard Deviation 0.02
|
-0.00 Giga cells per liter
Standard Deviation 0.02
|
0.01 Giga cells per liter
Standard Deviation 0.02
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Baseophil count, Day 15
|
0.01 Giga cells per liter
Standard Deviation 0.03
|
0.01 Giga cells per liter
Standard Deviation 0.03
|
-0.00 Giga cells per liter
Standard Deviation 0.02
|
-0.00 Giga cells per liter
Standard Deviation 0.02
|
0.01 Giga cells per liter
Standard Deviation 0.02
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Eosinophil count, Day 35
|
-0.01 Giga cells per liter
Standard Deviation 0.14
|
0.03 Giga cells per liter
Standard Deviation 0.24
|
-0.02 Giga cells per liter
Standard Deviation 0.11
|
0.05 Giga cells per liter
Standard Deviation 0.21
|
-0.02 Giga cells per liter
Standard Deviation 0.15
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Lymphocyte count, Day 8
|
0.20 Giga cells per liter
Standard Deviation 0.59
|
0.10 Giga cells per liter
Standard Deviation 0.46
|
0.12 Giga cells per liter
Standard Deviation 0.53
|
0.20 Giga cells per liter
Standard Deviation 0.58
|
0.12 Giga cells per liter
Standard Deviation 0.44
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Lymphocyte count, Day 15
|
0.10 Giga cells per liter
Standard Deviation 0.58
|
0.16 Giga cells per liter
Standard Deviation 0.41
|
0.11 Giga cells per liter
Standard Deviation 0.46
|
0.05 Giga cells per liter
Standard Deviation 0.46
|
0.22 Giga cells per liter
Standard Deviation 0.52
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Lymphocyte count, Day 22
|
0.17 Giga cells per liter
Standard Deviation 0.54
|
0.22 Giga cells per liter
Standard Deviation 0.43
|
-0.00 Giga cells per liter
Standard Deviation 0.43
|
0.04 Giga cells per liter
Standard Deviation 0.36
|
0.14 Giga cells per liter
Standard Deviation 0.46
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Lymphocyte count, Day 28
|
-0.03 Giga cells per liter
Standard Deviation 0.49
|
0.49 Giga cells per liter
Standard Deviation 0.47
|
-0.02 Giga cells per liter
Standard Deviation 0.47
|
-0.07 Giga cells per liter
Standard Deviation 0.47
|
0.05 Giga cells per liter
Standard Deviation 0.48
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Lymphocyte count, Day 35
|
0.15 Giga cells per liter
Standard Deviation 0.58
|
0.18 Giga cells per liter
Standard Deviation 0.43
|
0.06 Giga cells per liter
Standard Deviation 0.46
|
0.10 Giga cells per liter
Standard Deviation 0.57
|
0.16 Giga cells per liter
Standard Deviation 0.45
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Monocyte count, Day 8
|
0.02 Giga cells per liter
Standard Deviation 0.16
|
0.03 Giga cells per liter
Standard Deviation 0.13
|
0.04 Giga cells per liter
Standard Deviation 0.15
|
0.05 Giga cells per liter
Standard Deviation 0.18
|
0.04 Giga cells per liter
Standard Deviation 0.11
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Monocyte count, Day 15
|
0.02 Giga cells per liter
Standard Deviation 0.18
|
0.04 Giga cells per liter
Standard Deviation 0.12
|
0.04 Giga cells per liter
Standard Deviation 0.14
|
0.04 Giga cells per liter
Standard Deviation 0.15
|
0.02 Giga cells per liter
Standard Deviation 0.12
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Monocyte count, Day 22
|
0.05 Giga cells per liter
Standard Deviation 0.19
|
0.01 Giga cells per liter
Standard Deviation 0.13
|
0.00 Giga cells per liter
Standard Deviation 0.18
|
0.05 Giga cells per liter
Standard Deviation 0.16
|
0.05 Giga cells per liter
Standard Deviation 0.13
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Monocyte count, Day 28
|
-0.03 Giga cells per liter
Standard Deviation 0.15
|
-0.00 Giga cells per liter
Standard Deviation 0.13
|
-0.01 Giga cells per liter
Standard Deviation 0.11
|
0.00 Giga cells per liter
Standard Deviation 0.17
|
0.00 Giga cells per liter
Standard Deviation 0.11
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Monocyte count, Day 35
|
0.02 Giga cells per liter
Standard Deviation 0.15
|
0.00 Giga cells per liter
Standard Deviation 0.15
|
-0.01 Giga cells per liter
Standard Deviation 0.15
|
0.02 Giga cells per liter
Standard Deviation 0.16
|
0.03 Giga cells per liter
Standard Deviation 0.11
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Neutrophil count, Day 8
|
0.37 Giga cells per liter
Standard Deviation 1.29
|
0.11 Giga cells per liter
Standard Deviation 1.05
|
0.10 Giga cells per liter
Standard Deviation 1.23
|
0.03 Giga cells per liter
Standard Deviation 1.11
|
0.01 Giga cells per liter
Standard Deviation 1.08
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Neutrophil count, Day 15
|
0.55 Giga cells per liter
Standard Deviation 1.19
|
0.27 Giga cells per liter
Standard Deviation 0.88
|
0.31 Giga cells per liter
Standard Deviation 1.27
|
0.46 Giga cells per liter
Standard Deviation 1.40
|
0.15 Giga cells per liter
Standard Deviation 0.83
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Neutrophil count, Day 22
|
0.56 Giga cells per liter
Standard Deviation 1.31
|
0.31 Giga cells per liter
Standard Deviation 0.71
|
0.14 Giga cells per liter
Standard Deviation 1.38
|
0.20 Giga cells per liter
Standard Deviation 1.59
|
-0.07 Giga cells per liter
Standard Deviation 0.82
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Neutrophil count, Day 28
|
0.35 Giga cells per liter
Standard Deviation 1.23
|
-0.18 Giga cells per liter
Standard Deviation 0.96
|
0.19 Giga cells per liter
Standard Deviation 1.21
|
0.26 Giga cells per liter
Standard Deviation 1.28
|
0.08 Giga cells per liter
Standard Deviation 1.34
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Neutrophil count, Day 35
|
0.29 Giga cells per liter
Standard Deviation 1.18
|
0.09 Giga cells per liter
Standard Deviation 0.63
|
0.28 Giga cells per liter
Standard Deviation 1.13
|
0.55 Giga cells per liter
Standard Deviation 1.40
|
0.05 Giga cells per liter
Standard Deviation 1.27
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Platelet count, Day 8
|
4.03 Giga cells per liter
Standard Deviation 40.19
|
2.34 Giga cells per liter
Standard Deviation 26.94
|
12.14 Giga cells per liter
Standard Deviation 28.82
|
5.75 Giga cells per liter
Standard Deviation 23.95
|
6.37 Giga cells per liter
Standard Deviation 35.76
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Platelet count, Day 15
|
13.45 Giga cells per liter
Standard Deviation 39.23
|
13.10 Giga cells per liter
Standard Deviation 28.86
|
15.40 Giga cells per liter
Standard Deviation 30.99
|
7.73 Giga cells per liter
Standard Deviation 28.91
|
15.19 Giga cells per liter
Standard Deviation 41.90
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Platelet count, Day 22
|
9.49 Giga cells per liter
Standard Deviation 42.29
|
16.42 Giga cells per liter
Standard Deviation 27.73
|
19.70 Giga cells per liter
Standard Deviation 29.51
|
4.49 Giga cells per liter
Standard Deviation 30.38
|
9.28 Giga cells per liter
Standard Deviation 33.79
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Platelet count, Day 28
|
3.81 Giga cells per liter
Standard Deviation 45.00
|
7.11 Giga cells per liter
Standard Deviation 21.05
|
5.22 Giga cells per liter
Standard Deviation 34.65
|
8.73 Giga cells per liter
Standard Deviation 43.33
|
-3.05 Giga cells per liter
Standard Deviation 33.65
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
Platelet count, Day 35
|
6.27 Giga cells per liter
Standard Deviation 42.88
|
11.58 Giga cells per liter
Standard Deviation 26.85
|
20.65 Giga cells per liter
Standard Deviation 35.89
|
15.75 Giga cells per liter
Standard Deviation 37.58
|
10.89 Giga cells per liter
Standard Deviation 31.69
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
WBC count, Day 8
|
0.43 Giga cells per liter
Standard Deviation 1.66
|
0.37 Giga cells per liter
Standard Deviation 1.27
|
0.09 Giga cells per liter
Standard Deviation 1.45
|
0.22 Giga cells per liter
Standard Deviation 1.49
|
0.15 Giga cells per liter
Standard Deviation 1.36
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
WBC count, Day 15
|
0.67 Giga cells per liter
Standard Deviation 1.36
|
0.59 Giga cells per liter
Standard Deviation 1.10
|
0.44 Giga cells per liter
Standard Deviation 1.33
|
0.49 Giga cells per liter
Standard Deviation 1.60
|
0.35 Giga cells per liter
Standard Deviation 0.94
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
WBC count, Day 22
|
0.75 Giga cells per liter
Standard Deviation 1.64
|
0.58 Giga cells per liter
Standard Deviation 0.94
|
0.18 Giga cells per liter
Standard Deviation 1.62
|
0.31 Giga cells per liter
Standard Deviation 1.76
|
0.15 Giga cells per liter
Standard Deviation 0.92
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
WBC count, Day 28
|
0.21 Giga cells per liter
Standard Deviation 1.56
|
0.03 Giga cells per liter
Standard Deviation 1.20
|
0.02 Giga cells per liter
Standard Deviation 1.41
|
0.20 Giga cells per liter
Standard Deviation 1.46
|
0.12 Giga cells per liter
Standard Deviation 1.43
|
|
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and White Blood Cell (WBC) Count Over Time
WBC count, Day 35
|
0.29 Giga cells per liter
Standard Deviation 1.53
|
0.34 Giga cells per liter
Standard Deviation 0.90
|
0.26 Giga cells per liter
Standard Deviation 1.21
|
0.66 Giga cells per liter
Standard Deviation 1.68
|
0.23 Giga cells per liter
Standard Deviation 1.29
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter of Red Blood Cell (RBC) Count Over Time
Day 8
|
0.03 Trillion cells per liter
Standard Deviation 0.31
|
-0.02 Trillion cells per liter
Standard Deviation 0.24
|
0.03 Trillion cells per liter
Standard Deviation 0.23
|
0.03 Trillion cells per liter
Standard Deviation 0.20
|
-0.02 Trillion cells per liter
Standard Deviation 0.19
|
|
Change From Baseline in Hematology Parameter of Red Blood Cell (RBC) Count Over Time
Day 15
|
0.02 Trillion cells per liter
Standard Deviation 0.39
|
-0.04 Trillion cells per liter
Standard Deviation 0.22
|
-0.03 Trillion cells per liter
Standard Deviation 0.21
|
0.02 Trillion cells per liter
Standard Deviation 0.24
|
0.01 Trillion cells per liter
Standard Deviation 0.19
|
|
Change From Baseline in Hematology Parameter of Red Blood Cell (RBC) Count Over Time
Day 22
|
0.03 Trillion cells per liter
Standard Deviation 0.36
|
-0.04 Trillion cells per liter
Standard Deviation 0.22
|
-0.01 Trillion cells per liter
Standard Deviation 0.27
|
-0.01 Trillion cells per liter
Standard Deviation 0.20
|
0.04 Trillion cells per liter
Standard Deviation 0.48
|
|
Change From Baseline in Hematology Parameter of Red Blood Cell (RBC) Count Over Time
Day 28
|
-0.10 Trillion cells per liter
Standard Deviation 0.38
|
-0.11 Trillion cells per liter
Standard Deviation 0.23
|
-0.09 Trillion cells per liter
Standard Deviation 0.33
|
-0.12 Trillion cells per liter
Standard Deviation 0.23
|
-0.02 Trillion cells per liter
Standard Deviation 0.25
|
|
Change From Baseline in Hematology Parameter of Red Blood Cell (RBC) Count Over Time
Day 35
|
-0.10 Trillion cells per liter
Standard Deviation 0.35
|
-0.14 Trillion cells per liter
Standard Deviation 0.21
|
-0.13 Trillion cells per liter
Standard Deviation 0.41
|
-0.12 Trillion cells per liter
Standard Deviation 0.21
|
-0.08 Trillion cells per liter
Standard Deviation 0.27
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter of Hematocrit Over Time
Day 8
|
0.00 Ratio
Standard Deviation 0.03
|
-0.00 Ratio
Standard Deviation 0.03
|
0.00 Ratio
Standard Deviation 0.03
|
0.00 Ratio
Standard Deviation 0.02
|
-0.00 Ratio
Standard Deviation 0.02
|
|
Change From Baseline in Hematology Parameter of Hematocrit Over Time
Day 15
|
0.00 Ratio
Standard Deviation 0.04
|
-0.00 Ratio
Standard Deviation 0.02
|
-0.00 Ratio
Standard Deviation 0.02
|
-0.00 Ratio
Standard Deviation 0.02
|
0.00 Ratio
Standard Deviation 0.02
|
|
Change From Baseline in Hematology Parameter of Hematocrit Over Time
Day 22
|
0.01 Ratio
Standard Deviation 0.03
|
-0.00 Ratio
Standard Deviation 0.02
|
-0.00 Ratio
Standard Deviation 0.03
|
-0.00 Ratio
Standard Deviation 0.02
|
0.01 Ratio
Standard Deviation 0.05
|
|
Change From Baseline in Hematology Parameter of Hematocrit Over Time
Day 28
|
-0.01 Ratio
Standard Deviation 0.04
|
-0.01 Ratio
Standard Deviation 0.02
|
-0.01 Ratio
Standard Deviation 0.04
|
-0.01 Ratio
Standard Deviation 0.03
|
-0.00 Ratio
Standard Deviation 0.02
|
|
Change From Baseline in Hematology Parameter of Hematocrit Over Time
Day 35
|
-0.01 Ratio
Standard Deviation 0.03
|
-0.01 Ratio
Standard Deviation 0.02
|
-0.01 Ratio
Standard Deviation 0.03
|
-0.01 Ratio
Standard Deviation 0.02
|
-0.00 Ratio
Standard Deviation 0.03
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter of Hemoglobin Over Time
Day 8
|
1.49 Gram per liter
Standard Deviation 9.28
|
-0.03 Gram per liter
Standard Deviation 7.36
|
0.47 Gram per liter
Standard Deviation 8.03
|
1.44 Gram per liter
Standard Deviation 6.58
|
-0.75 Gram per liter
Standard Deviation 5.17
|
|
Change From Baseline in Hematology Parameter of Hemoglobin Over Time
Day 15
|
1.09 Gram per liter
Standard Deviation 11.65
|
-0.32 Gram per liter
Standard Deviation 7.21
|
-0.81 Gram per liter
Standard Deviation 8.25
|
0.40 Gram per liter
Standard Deviation 6.70
|
0.31 Gram per liter
Standard Deviation 5.13
|
|
Change From Baseline in Hematology Parameter of Hemoglobin Over Time
Day 22
|
1.05 Gram per liter
Standard Deviation 10.71
|
-0.57 Gram per liter
Standard Deviation 7.56
|
-0.82 Gram per liter
Standard Deviation 9.70
|
-0.05 Gram per liter
Standard Deviation 5.92
|
-1.08 Gram per liter
Standard Deviation 5.87
|
|
Change From Baseline in Hematology Parameter of Hemoglobin Over Time
Day 28
|
-2.60 Gram per liter
Standard Deviation 11.34
|
-2.32 Gram per liter
Standard Deviation 7.83
|
-2.58 Gram per liter
Standard Deviation 10.49
|
-3.83 Gram per liter
Standard Deviation 6.88
|
-0.43 Gram per liter
Standard Deviation 7.34
|
|
Change From Baseline in Hematology Parameter of Hemoglobin Over Time
Day 35
|
-2.33 Gram per liter
Standard Deviation 11.10
|
-3.50 Gram per liter
Standard Deviation 7.53
|
-4.75 Gram per liter
Standard Deviation 9.87
|
-3.08 Gram per liter
Standard Deviation 6.16
|
-2.19 Gram per liter
Standard Deviation 8.37
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Over Time
Day 8
|
0.15 Picogram per cell
Standard Deviation 0.79
|
0.23 Picogram per cell
Standard Deviation 0.62
|
-0.16 Picogram per cell
Standard Deviation 0.82
|
0.17 Picogram per cell
Standard Deviation 0.67
|
0.00 Picogram per cell
Standard Deviation 0.72
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Over Time
Day 15
|
0.23 Picogram per cell
Standard Deviation 1.14
|
0.27 Picogram per cell
Standard Deviation 0.63
|
-0.03 Picogram per cell
Standard Deviation 0.81
|
-0.08 Picogram per cell
Standard Deviation 0.53
|
0.03 Picogram per cell
Standard Deviation 0.58
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Over Time
Day 22
|
0.14 Picogram per cell
Standard Deviation 0.79
|
0.14 Picogram per cell
Standard Deviation 0.65
|
-0.18 Picogram per cell
Standard Deviation 0.90
|
0.10 Picogram per cell
Standard Deviation 0.64
|
-0.24 Picogram per cell
Standard Deviation 1.79
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Over Time
Day 28
|
0.11 Picogram per cell
Standard Deviation 0.96
|
0.39 Picogram per cell
Standard Deviation 0.67
|
0.03 Picogram per cell
Standard Deviation 0.94
|
0.00 Picogram per cell
Standard Deviation 0.60
|
0.10 Picogram per cell
Standard Deviation 0.74
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Over Time
Day 35
|
0.05 Picogram per cell
Standard Deviation 1.36
|
0.38 Picogram per cell
Standard Deviation 0.66
|
-0.11 Picogram per cell
Standard Deviation 1.74
|
0.08 Picogram per cell
Standard Deviation 0.73
|
0.11 Picogram per cell
Standard Deviation 0.82
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Concentration Over Time
Day 8
|
0.00 Gram hemoglobin per liter
Standard Deviation 7.56
|
0.77 Gram hemoglobin per liter
Standard Deviation 8.39
|
0.56 Gram hemoglobin per liter
Standard Deviation 9.24
|
3.33 Gram hemoglobin per liter
Standard Deviation 9.24
|
-1.43 Gram hemoglobin per liter
Standard Deviation 8.10
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Concentration Over Time
Day 15
|
0.31 Gram hemoglobin per liter
Standard Deviation 8.22
|
2.16 Gram hemoglobin per liter
Standard Deviation 7.50
|
-0.63 Gram hemoglobin per liter
Standard Deviation 11.34
|
0.31 Gram hemoglobin per liter
Standard Deviation 8.61
|
0.59 Gram hemoglobin per liter
Standard Deviation 7.36
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Concentration Over Time
Day 22
|
-1.25 Gram hemoglobin per liter
Standard Deviation 8.33
|
0.25 Gram hemoglobin per liter
Standard Deviation 9.47
|
-2.29 Gram hemoglobin per liter
Standard Deviation 11.65
|
1.56 Gram hemoglobin per liter
Standard Deviation 7.67
|
-4.00 Gram hemoglobin per liter
Standard Deviation 21.58
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Concentration Over Time
Day 28
|
1.85 Gram hemoglobin per liter
Standard Deviation 8.34
|
1.47 Gram hemoglobin per liter
Standard Deviation 6.57
|
-0.59 Gram hemoglobin per liter
Standard Deviation 12.78
|
0.00 Gram hemoglobin per liter
Standard Deviation 8.77
|
-1.56 Gram hemoglobin per liter
Standard Deviation 8.08
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Hemoglobin Concentration Over Time
Day 35
|
0.32 Gram hemoglobin per liter
Standard Deviation 11.69
|
-0.81 Gram hemoglobin per liter
Standard Deviation 7.22
|
0.32 Gram hemoglobin per liter
Standard Deviation 12.51
|
-1.54 Gram hemoglobin per liter
Standard Deviation 7.32
|
-2.35 Gram hemoglobin per liter
Standard Deviation 7.81
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Volume Over Time
Day 8
|
0.28 Femtoliter
Standard Deviation 1.77
|
0.18 Femtoliter
Standard Deviation 1.68
|
-0.33 Femtoliter
Standard Deviation 2.24
|
-0.17 Femtoliter
Standard Deviation 1.53
|
0.20 Femtoliter
Standard Deviation 1.21
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Volume Over Time
Day 15
|
0.69 Femtoliter
Standard Deviation 3.35
|
0.11 Femtoliter
Standard Deviation 1.54
|
-0.06 Femtoliter
Standard Deviation 2.71
|
-0.03 Femtoliter
Standard Deviation 1.45
|
0.29 Femtoliter
Standard Deviation 1.29
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Volume Over Time
Day 22
|
0.59 Femtoliter
Standard Deviation 1.70
|
0.05 Femtoliter
Standard Deviation 1.72
|
0.03 Femtoliter
Standard Deviation 2.27
|
0.13 Femtoliter
Standard Deviation 1.66
|
0.17 Femtoliter
Standard Deviation 1.98
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Volume Over Time
Day 28
|
-0.19 Femtoliter
Standard Deviation 2.43
|
0.29 Femtoliter
Standard Deviation 1.17
|
0.29 Femtoliter
Standard Deviation 2.70
|
0.22 Femtoliter
Standard Deviation 1.72
|
0.81 Femtoliter
Standard Deviation 1.89
|
|
Change From Baseline in Hematology Parameter of Mean Corpuscular Volume Over Time
Day 35
|
0.74 Femtoliter
Standard Deviation 3.01
|
0.73 Femtoliter
Standard Deviation 1.63
|
-0.71 Femtoliter
Standard Deviation 4.27
|
0.77 Femtoliter
Standard Deviation 1.70
|
1.00 Femtoliter
Standard Deviation 1.74
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 28 and Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Coagulation Parameters of Activated Partial Thromplastin Time (aPTT) and Prothrombin Time (PT) Over Time
aPTT, Day 28
|
1.51 Seconds
Standard Deviation 9.88
|
-1.58 Seconds
Standard Deviation 6.98
|
1.41 Seconds
Standard Deviation 13.03
|
1.26 Seconds
Standard Deviation 10.07
|
0.53 Seconds
Standard Deviation 6.78
|
|
Change From Baseline in Coagulation Parameters of Activated Partial Thromplastin Time (aPTT) and Prothrombin Time (PT) Over Time
aPTT, Day 35
|
-1.73 Seconds
Standard Deviation 4.28
|
-1.46 Seconds
Standard Deviation 4.31
|
-1.28 Seconds
Standard Deviation 4.33
|
-0.84 Seconds
Standard Deviation 5.26
|
-0.43 Seconds
Standard Deviation 6.99
|
|
Change From Baseline in Coagulation Parameters of Activated Partial Thromplastin Time (aPTT) and Prothrombin Time (PT) Over Time
PT, Day 28
|
0.18 Seconds
Standard Deviation 2.68
|
0.20 Seconds
Standard Deviation 2.99
|
-0.18 Seconds
Standard Deviation 1.43
|
-0.36 Seconds
Standard Deviation 1.99
|
-0.28 Seconds
Standard Deviation 1.62
|
|
Change From Baseline in Coagulation Parameters of Activated Partial Thromplastin Time (aPTT) and Prothrombin Time (PT) Over Time
PT, Day 35
|
-0.45 Seconds
Standard Deviation 1.13
|
-0.26 Seconds
Standard Deviation 0.83
|
-0.47 Seconds
Standard Deviation 2.07
|
-0.44 Seconds
Standard Deviation 0.94
|
-0.49 Seconds
Standard Deviation 1.62
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Day 28 and Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Coagulation Parameter of International Normalized Ratio Over Time
Day 28
|
0.02 Ratio
Standard Deviation 0.24
|
0.01 Ratio
Standard Deviation 0.24
|
-0.01 Ratio
Standard Deviation 0.11
|
-0.03 Ratio
Standard Deviation 0.16
|
-0.02 Ratio
Standard Deviation 0.13
|
|
Change From Baseline in Coagulation Parameter of International Normalized Ratio Over Time
Day 35
|
-0.03 Ratio
Standard Deviation 0.09
|
-0.02 Ratio
Standard Deviation 0.07
|
-0.04 Ratio
Standard Deviation 0.16
|
-0.04 Ratio
Standard Deviation 0.07
|
-0.04 Ratio
Standard Deviation 0.13
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALT, Day 8
|
-0.90 International units per liter
Standard Deviation 6.99
|
1.18 International units per liter
Standard Deviation 10.46
|
-1.53 International units per liter
Standard Deviation 6.48
|
-0.46 International units per liter
Standard Deviation 8.49
|
0.90 International units per liter
Standard Deviation 8.33
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALT, Day 15
|
-0.54 International units per liter
Standard Deviation 7.99
|
-0.21 International units per liter
Standard Deviation 10.54
|
-2.69 International units per liter
Standard Deviation 6.69
|
-1.95 International units per liter
Standard Deviation 8.92
|
1.03 International units per liter
Standard Deviation 15.17
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALT, Day 22
|
3.05 International units per liter
Standard Deviation 13.37
|
-0.41 International units per liter
Standard Deviation 10.98
|
-0.21 International units per liter
Standard Deviation 9.78
|
-3.71 International units per liter
Standard Deviation 11.15
|
0.13 International units per liter
Standard Deviation 13.64
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALT, Day 28
|
0.56 International units per liter
Standard Deviation 13.18
|
-0.47 International units per liter
Standard Deviation 13.17
|
-2.27 International units per liter
Standard Deviation 9.81
|
-3.86 International units per liter
Standard Deviation 11.10
|
-2.79 International units per liter
Standard Deviation 11.14
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALT, Day 35
|
-0.38 International units per liter
Standard Deviation 9.43
|
-0.97 International units per liter
Standard Deviation 10.85
|
-3.06 International units per liter
Standard Deviation 9.14
|
-3.13 International units per liter
Standard Deviation 11.78
|
-2.49 International units per liter
Standard Deviation 11.86
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALP, Day 8
|
-0.63 International units per liter
Standard Deviation 9.80
|
-1.60 International units per liter
Standard Deviation 8.15
|
-3.24 International units per liter
Standard Deviation 9.00
|
0.63 International units per liter
Standard Deviation 9.90
|
-3.22 International units per liter
Standard Deviation 7.60
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALP, Day 15
|
-4.17 International units per liter
Standard Deviation 14.55
|
-2.05 International units per liter
Standard Deviation 12.83
|
-5.67 International units per liter
Standard Deviation 18.08
|
-1.65 International units per liter
Standard Deviation 10.35
|
-1.61 International units per liter
Standard Deviation 15.02
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALP, Day 22
|
-0.55 International units per liter
Standard Deviation 17.35
|
-0.22 International units per liter
Standard Deviation 13.95
|
-2.08 International units per liter
Standard Deviation 19.56
|
-2.20 International units per liter
Standard Deviation 12.29
|
-3.17 International units per liter
Standard Deviation 10.10
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALP, Day 28
|
-1.34 International units per liter
Standard Deviation 19.89
|
-3.33 International units per liter
Standard Deviation 14.41
|
-4.61 International units per liter
Standard Deviation 18.06
|
-4.05 International units per liter
Standard Deviation 15.79
|
-4.73 International units per liter
Standard Deviation 12.20
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
ALP, Day 35
|
-2.10 International units per liter
Standard Deviation 15.76
|
-2.71 International units per liter
Standard Deviation 13.71
|
-6.34 International units per liter
Standard Deviation 16.37
|
-4.69 International units per liter
Standard Deviation 16.79
|
-5.95 International units per liter
Standard Deviation 12.74
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
AST, Day 8
|
-1.25 International units per liter
Standard Deviation 6.30
|
-0.63 International units per liter
Standard Deviation 6.92
|
-1.18 International units per liter
Standard Deviation 10.44
|
0.46 International units per liter
Standard Deviation 4.89
|
-1.33 International units per liter
Standard Deviation 10.28
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
AST, Day 15
|
-0.54 International units per liter
Standard Deviation 6.27
|
-0.38 International units per liter
Standard Deviation 9.60
|
-2.85 International units per liter
Standard Deviation 11.39
|
0.37 International units per liter
Standard Deviation 5.27
|
-0.97 International units per liter
Standard Deviation 13.71
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
AST, Day 22
|
1.47 International units per liter
Standard Deviation 6.43
|
-0.95 International units per liter
Standard Deviation 11.51
|
-0.97 International units per liter
Standard Deviation 12.87
|
-1.50 International units per liter
Standard Deviation 6.33
|
-1.36 International units per liter
Standard Deviation 11.82
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
AST, Day 28
|
-1.39 International units per liter
Standard Deviation 6.93
|
-0.69 International units per liter
Standard Deviation 9.92
|
-2.23 International units per liter
Standard Deviation 11.76
|
-1.44 International units per liter
Standard Deviation 4.95
|
-2.28 International units per liter
Standard Deviation 11.28
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
AST, Day 35
|
-1.38 International units per liter
Standard Deviation 6.52
|
-0.82 International units per liter
Standard Deviation 10.05
|
-1.88 International units per liter
Standard Deviation 12.15
|
-1.88 International units per liter
Standard Deviation 5.21
|
-2.14 International units per liter
Standard Deviation 11.95
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
Creatinine phosphokinase, Day 8
|
11.25 International units per liter
Standard Deviation 79.26
|
-10.95 International units per liter
Standard Deviation 84.04
|
-3.11 International units per liter
Standard Deviation 30.12
|
-8.37 International units per liter
Standard Deviation 100.00
|
-4.05 International units per liter
Standard Deviation 30.14
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
Creatinine phosphokinase, Day 15
|
4.46 International units per liter
Standard Deviation 33.64
|
-10.23 International units per liter
Standard Deviation 77.79
|
-7.06 International units per liter
Standard Deviation 43.44
|
-0.05 International units per liter
Standard Deviation 101.77
|
-9.03 International units per liter
Standard Deviation 39.62
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
Creatinine phosphokinase, Day 22
|
27.54 International units per liter
Standard Deviation 97.86
|
-19.40 International units per liter
Standard Deviation 74.31
|
6.47 International units per liter
Standard Deviation 33.44
|
-9.18 International units per liter
Standard Deviation 100.75
|
0.28 International units per liter
Standard Deviation 33.55
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
Creatinine phosphokinase, Day 28
|
2.61 International units per liter
Standard Deviation 32.25
|
-15.03 International units per liter
Standard Deviation 84.44
|
12.65 International units per liter
Standard Deviation 40.68
|
-3.47 International units per liter
Standard Deviation 110.21
|
-3.74 International units per liter
Standard Deviation 51.30
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
Creatinine phosphokinase, Day 35
|
0.38 International units per liter
Standard Deviation 31.87
|
-12.58 International units per liter
Standard Deviation 82.07
|
8.30 International units per liter
Standard Deviation 33.05
|
-4.33 International units per liter
Standard Deviation 104.54
|
-4.65 International units per liter
Standard Deviation 23.19
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
LDH, Day 8
|
0.03 International units per liter
Standard Deviation 20.69
|
1.51 International units per liter
Standard Deviation 20.44
|
-5.23 International units per liter
Standard Deviation 18.38
|
-0.54 International units per liter
Standard Deviation 14.93
|
-9.27 International units per liter
Standard Deviation 55.02
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
LDH, Day 15
|
0.58 International units per liter
Standard Deviation 20.51
|
-2.45 International units per liter
Standard Deviation 23.63
|
-6.09 International units per liter
Standard Deviation 29.60
|
-2.64 International units per liter
Standard Deviation 16.74
|
-3.31 International units per liter
Standard Deviation 52.15
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
LDH, Day 22
|
-0.33 International units per liter
Standard Deviation 21.26
|
-2.34 International units per liter
Standard Deviation 22.19
|
-3.61 International units per liter
Standard Deviation 22.03
|
-3.42 International units per liter
Standard Deviation 16.53
|
-8.84 International units per liter
Standard Deviation 58.19
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
LDH, Day 28
|
-5.04 International units per liter
Standard Deviation 19.71
|
-7.44 International units per liter
Standard Deviation 18.31
|
-6.70 International units per liter
Standard Deviation 16.99
|
-1.48 International units per liter
Standard Deviation 16.83
|
-11.27 International units per liter
Standard Deviation 56.13
|
|
Change From Baseline in Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotrasferase (AST), Alkaline Phosphatase (ALP), Creatinine Phosphokinase and Lactate Dehydrogenase (LDH) Over Time
LDH, Day 35
|
-1.74 International units per liter
Standard Deviation 20.90
|
2.19 International units per liter
Standard Deviation 25.99
|
-1.65 International units per liter
Standard Deviation 23.37
|
-3.68 International units per liter
Standard Deviation 16.18
|
-7.47 International units per liter
Standard Deviation 60.72
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Bicarbonate, Day 8
|
0.78 Micromole (mmol) per liter
Standard Deviation 3.01
|
0.62 Micromole (mmol) per liter
Standard Deviation 2.40
|
0.13 Micromole (mmol) per liter
Standard Deviation 2.48
|
-0.17 Micromole (mmol) per liter
Standard Deviation 2.64
|
0.74 Micromole (mmol) per liter
Standard Deviation 2.69
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Bicarbonate, Day 15
|
1.47 Micromole (mmol) per liter
Standard Deviation 2.68
|
0.41 Micromole (mmol) per liter
Standard Deviation 2.45
|
0.42 Micromole (mmol) per liter
Standard Deviation 2.52
|
0.03 Micromole (mmol) per liter
Standard Deviation 2.86
|
0.85 Micromole (mmol) per liter
Standard Deviation 2.36
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Bicarbonate, Day 22
|
1.45 Micromole (mmol) per liter
Standard Deviation 2.69
|
0.90 Micromole (mmol) per liter
Standard Deviation 2.96
|
0.03 Micromole (mmol) per liter
Standard Deviation 2.49
|
0.00 Micromole (mmol) per liter
Standard Deviation 2.60
|
0.65 Micromole (mmol) per liter
Standard Deviation 2.71
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Bicarbonate, Day 28
|
0.40 Micromole (mmol) per liter
Standard Deviation 2.66
|
-0.37 Micromole (mmol) per liter
Standard Deviation 2.67
|
-0.13 Micromole (mmol) per liter
Standard Deviation 2.42
|
-0.68 Micromole (mmol) per liter
Standard Deviation 1.97
|
-0.09 Micromole (mmol) per liter
Standard Deviation 2.61
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Bicarbonate, Day 35
|
0.51 Micromole (mmol) per liter
Standard Deviation 2.61
|
0.60 Micromole (mmol) per liter
Standard Deviation 2.65
|
-0.14 Micromole (mmol) per liter
Standard Deviation 2.31
|
-0.48 Micromole (mmol) per liter
Standard Deviation 2.75
|
0.68 Micromole (mmol) per liter
Standard Deviation 2.96
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
BUN, Day 8
|
0.30 Micromole (mmol) per liter
Standard Deviation 2.05
|
0.29 Micromole (mmol) per liter
Standard Deviation 1.39
|
0.15 Micromole (mmol) per liter
Standard Deviation 1.40
|
0.03 Micromole (mmol) per liter
Standard Deviation 1.19
|
-0.09 Micromole (mmol) per liter
Standard Deviation 1.40
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
BUN, Day 15
|
0.16 Micromole (mmol) per liter
Standard Deviation 2.19
|
0.15 Micromole (mmol) per liter
Standard Deviation 1.00
|
0.42 Micromole (mmol) per liter
Standard Deviation 1.33
|
0.36 Micromole (mmol) per liter
Standard Deviation 1.46
|
-0.06 Micromole (mmol) per liter
Standard Deviation 1.43
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
BUN, Day 22
|
0.36 Micromole (mmol) per liter
Standard Deviation 2.01
|
0.27 Micromole (mmol) per liter
Standard Deviation 1.16
|
0.01 Micromole (mmol) per liter
Standard Deviation 1.46
|
0.16 Micromole (mmol) per liter
Standard Deviation 1.16
|
-0.03 Micromole (mmol) per liter
Standard Deviation 1.21
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
BUN, Day 28
|
0.91 Micromole (mmol) per liter
Standard Deviation 2.11
|
0.24 Micromole (mmol) per liter
Standard Deviation 1.29
|
-0.15 Micromole (mmol) per liter
Standard Deviation 1.49
|
0.09 Micromole (mmol) per liter
Standard Deviation 1.25
|
0.25 Micromole (mmol) per liter
Standard Deviation 1.39
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
BUN, Day 35
|
0.35 Micromole (mmol) per liter
Standard Deviation 1.78
|
0.22 Micromole (mmol) per liter
Standard Deviation 1.40
|
-0.57 Micromole (mmol) per liter
Standard Deviation 1.37
|
-0.11 Micromole (mmol) per liter
Standard Deviation 1.40
|
-0.07 Micromole (mmol) per liter
Standard Deviation 1.51
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Calcium, Day 8
|
0.02 Micromole (mmol) per liter
Standard Deviation 0.12
|
0.03 Micromole (mmol) per liter
Standard Deviation 0.11
|
0.05 Micromole (mmol) per liter
Standard Deviation 0.10
|
0.02 Micromole (mmol) per liter
Standard Deviation 0.09
|
0.03 Micromole (mmol) per liter
Standard Deviation 0.09
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Calcium, Day 15
|
0.00 Micromole (mmol) per liter
Standard Deviation 0.15
|
0.01 Micromole (mmol) per liter
Standard Deviation 0.10
|
0.05 Micromole (mmol) per liter
Standard Deviation 0.12
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.10
|
0.04 Micromole (mmol) per liter
Standard Deviation 0.10
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Calcium, Day 22
|
0.01 Micromole (mmol) per liter
Standard Deviation 0.13
|
0.01 Micromole (mmol) per liter
Standard Deviation 0.10
|
0.05 Micromole (mmol) per liter
Standard Deviation 0.08
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.09
|
0.02 Micromole (mmol) per liter
Standard Deviation 0.08
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Calcium, Day 28
|
-0.02 Micromole (mmol) per liter
Standard Deviation 0.15
|
-0.03 Micromole (mmol) per liter
Standard Deviation 0.12
|
0.02 Micromole (mmol) per liter
Standard Deviation 0.11
|
-0.04 Micromole (mmol) per liter
Standard Deviation 0.10
|
0.00 Micromole (mmol) per liter
Standard Deviation 0.11
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Calcium, Day 35
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.11
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.09
|
0.02 Micromole (mmol) per liter
Standard Deviation 0.08
|
-0.02 Micromole (mmol) per liter
Standard Deviation 0.11
|
0.02 Micromole (mmol) per liter
Standard Deviation 0.11
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Chloride, Day 8
|
-0.14 Micromole (mmol) per liter
Standard Deviation 3.07
|
0.46 Micromole (mmol) per liter
Standard Deviation 2.96
|
0.12 Micromole (mmol) per liter
Standard Deviation 2.82
|
-0.80 Micromole (mmol) per liter
Standard Deviation 2.72
|
0.45 Micromole (mmol) per liter
Standard Deviation 2.44
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Chloride, Day 15
|
0.00 Micromole (mmol) per liter
Standard Deviation 3.16
|
0.29 Micromole (mmol) per liter
Standard Deviation 2.63
|
0.90 Micromole (mmol) per liter
Standard Deviation 2.50
|
-0.71 Micromole (mmol) per liter
Standard Deviation 3.39
|
0.24 Micromole (mmol) per liter
Standard Deviation 3.01
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Chloride, Day 22
|
-0.26 Micromole (mmol) per liter
Standard Deviation 3.27
|
0.45 Micromole (mmol) per liter
Standard Deviation 2.98
|
1.10 Micromole (mmol) per liter
Standard Deviation 3.11
|
-0.65 Micromole (mmol) per liter
Standard Deviation 3.00
|
0.57 Micromole (mmol) per liter
Standard Deviation 2.61
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Chloride, Day 28
|
0.17 Micromole (mmol) per liter
Standard Deviation 3.30
|
0.54 Micromole (mmol) per liter
Standard Deviation 3.06
|
0.43 Micromole (mmol) per liter
Standard Deviation 3.27
|
0.00 Micromole (mmol) per liter
Standard Deviation 3.45
|
-0.17 Micromole (mmol) per liter
Standard Deviation 2.78
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Chloride, Day 35
|
0.98 Micromole (mmol) per liter
Standard Deviation 2.88
|
1.40 Micromole (mmol) per liter
Standard Deviation 3.00
|
1.38 Micromole (mmol) per liter
Standard Deviation 3.13
|
0.95 Micromole (mmol) per liter
Standard Deviation 3.09
|
0.49 Micromole (mmol) per liter
Standard Deviation 3.00
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Magnesium, Day 8
|
0.00 Micromole (mmol) per liter
Standard Deviation 0.06
|
-0.02 Micromole (mmol) per liter
Standard Deviation 0.06
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
0.01 Micromole (mmol) per liter
Standard Deviation 0.07
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Magnesium, Day 15
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.07
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.04
|
0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Magnesium, Day 22
|
0.00 Micromole (mmol) per liter
Standard Deviation 0.07
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
0.00 Micromole (mmol) per liter
Standard Deviation 0.06
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.08
|
0.01 Micromole (mmol) per liter
Standard Deviation 0.08
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Magnesium, Day 28
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
-0.02 Micromole (mmol) per liter
Standard Deviation 0.06
|
0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.05
|
0.00 Micromole (mmol) per liter
Standard Deviation 0.06
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Magnesium, Day 35
|
-0.02 Micromole (mmol) per liter
Standard Deviation 0.08
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.08
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.07
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.06
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Phosphate, Day 8
|
-0.02 Micromole (mmol) per liter
Standard Deviation 0.19
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.18
|
-0.03 Micromole (mmol) per liter
Standard Deviation 0.20
|
0.03 Micromole (mmol) per liter
Standard Deviation 0.13
|
-0.02 Micromole (mmol) per liter
Standard Deviation 0.21
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Phosphate, Day 15
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.16
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.15
|
-0.04 Micromole (mmol) per liter
Standard Deviation 0.20
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.17
|
0.04 Micromole (mmol) per liter
Standard Deviation 0.21
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Phosphate, Day 22
|
0.04 Micromole (mmol) per liter
Standard Deviation 0.19
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.16
|
-0.03 Micromole (mmol) per liter
Standard Deviation 0.22
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.18
|
0.01 Micromole (mmol) per liter
Standard Deviation 0.21
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Phosphate, Day 28
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.19
|
0.02 Micromole (mmol) per liter
Standard Deviation 0.18
|
-0.03 Micromole (mmol) per liter
Standard Deviation 0.22
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.16
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.20
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Phosphate, Day 35
|
-0.04 Micromole (mmol) per liter
Standard Deviation 0.18
|
-0.01 Micromole (mmol) per liter
Standard Deviation 0.14
|
-0.02 Micromole (mmol) per liter
Standard Deviation 0.23
|
0.04 Micromole (mmol) per liter
Standard Deviation 0.21
|
-0.00 Micromole (mmol) per liter
Standard Deviation 0.20
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Potassium, Day 8
|
0.11 Micromole (mmol) per liter
Standard Deviation 0.38
|
0.27 Micromole (mmol) per liter
Standard Deviation 0.45
|
0.24 Micromole (mmol) per liter
Standard Deviation 0.47
|
0.19 Micromole (mmol) per liter
Standard Deviation 0.42
|
0.29 Micromole (mmol) per liter
Standard Deviation 0.48
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Potassium, Day 15
|
0.16 Micromole (mmol) per liter
Standard Deviation 0.35
|
0.25 Micromole (mmol) per liter
Standard Deviation 0.41
|
0.34 Micromole (mmol) per liter
Standard Deviation 0.47
|
0.13 Micromole (mmol) per liter
Standard Deviation 0.35
|
0.23 Micromole (mmol) per liter
Standard Deviation 0.46
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Potassium, Day 22
|
0.13 Micromole (mmol) per liter
Standard Deviation 0.40
|
0.28 Micromole (mmol) per liter
Standard Deviation 0.41
|
0.31 Micromole (mmol) per liter
Standard Deviation 0.51
|
0.14 Micromole (mmol) per liter
Standard Deviation 0.40
|
0.19 Micromole (mmol) per liter
Standard Deviation 0.53
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Potassium, Day 28
|
-0.02 Micromole (mmol) per liter
Standard Deviation 0.52
|
0.07 Micromole (mmol) per liter
Standard Deviation 0.37
|
0.03 Micromole (mmol) per liter
Standard Deviation 0.48
|
-0.20 Micromole (mmol) per liter
Standard Deviation 0.31
|
0.00 Micromole (mmol) per liter
Standard Deviation 0.43
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Potassium, Day 35
|
0.07 Micromole (mmol) per liter
Standard Deviation 0.45
|
0.23 Micromole (mmol) per liter
Standard Deviation 0.35
|
0.20 Micromole (mmol) per liter
Standard Deviation 0.44
|
0.10 Micromole (mmol) per liter
Standard Deviation 0.42
|
0.25 Micromole (mmol) per liter
Standard Deviation 0.59
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Sodium, Day 8
|
-0.33 Micromole (mmol) per liter
Standard Deviation 2.72
|
0.29 Micromole (mmol) per liter
Standard Deviation 2.62
|
0.05 Micromole (mmol) per liter
Standard Deviation 2.93
|
-0.41 Micromole (mmol) per liter
Standard Deviation 2.74
|
0.05 Micromole (mmol) per liter
Standard Deviation 2.48
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Sodium, Day 15
|
-0.53 Micromole (mmol) per liter
Standard Deviation 2.69
|
-0.31 Micromole (mmol) per liter
Standard Deviation 2.57
|
0.80 Micromole (mmol) per liter
Standard Deviation 2.90
|
-0.59 Micromole (mmol) per liter
Standard Deviation 3.19
|
0.10 Micromole (mmol) per liter
Standard Deviation 3.08
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Sodium, Day 22
|
-0.46 Micromole (mmol) per liter
Standard Deviation 2.34
|
0.29 Micromole (mmol) per liter
Standard Deviation 2.80
|
1.03 Micromole (mmol) per liter
Standard Deviation 3.06
|
-0.63 Micromole (mmol) per liter
Standard Deviation 2.83
|
0.31 Micromole (mmol) per liter
Standard Deviation 2.42
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Sodium, Day 28
|
-0.11 Micromole (mmol) per liter
Standard Deviation 3.35
|
-0.15 Micromole (mmol) per liter
Standard Deviation 2.82
|
0.73 Micromole (mmol) per liter
Standard Deviation 2.67
|
-0.40 Micromole (mmol) per liter
Standard Deviation 3.09
|
0.07 Micromole (mmol) per liter
Standard Deviation 2.87
|
|
Change From Baseline in Chemistry Parameter of Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Magnesium, Phosphate, Potassium and Sodium Over Time
Sodium, Day 35
|
0.07 Micromole (mmol) per liter
Standard Deviation 2.78
|
0.57 Micromole (mmol) per liter
Standard Deviation 3.01
|
1.10 Micromole (mmol) per liter
Standard Deviation 2.33
|
0.24 Micromole (mmol) per liter
Standard Deviation 2.41
|
0.71 Micromole (mmol) per liter
Standard Deviation 2.94
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Total bilirubin, Day 35
|
-0.33 Micromole per liter
Standard Deviation 3.72
|
-0.32 Micromole per liter
Standard Deviation 3.39
|
-1.81 Micromole per liter
Standard Deviation 5.34
|
-1.39 Micromole per liter
Standard Deviation 3.28
|
-0.62 Micromole per liter
Standard Deviation 4.24
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Uric acid, Day 8
|
-8.66 Micromole per liter
Standard Deviation 55.20
|
-22.90 Micromole per liter
Standard Deviation 48.36
|
-20.95 Micromole per liter
Standard Deviation 61.72
|
-26.20 Micromole per liter
Standard Deviation 66.02
|
1.38 Micromole per liter
Standard Deviation 38.94
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Uric acid, Day 15
|
-13.19 Micromole per liter
Standard Deviation 54.16
|
-20.29 Micromole per liter
Standard Deviation 39.59
|
-11.13 Micromole per liter
Standard Deviation 74.79
|
-7.70 Micromole per liter
Standard Deviation 63.59
|
-5.95 Micromole per liter
Standard Deviation 59.07
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Uric acid, Day 22
|
-3.55 Micromole per liter
Standard Deviation 53.46
|
-21.63 Micromole per liter
Standard Deviation 52.20
|
-13.61 Micromole per liter
Standard Deviation 57.87
|
-13.88 Micromole per liter
Standard Deviation 70.17
|
-1.40 Micromole per liter
Standard Deviation 46.23
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Uric acid, Day 28
|
6.20 Micromole per liter
Standard Deviation 74.17
|
-10.73 Micromole per liter
Standard Deviation 41.62
|
-6.00 Micromole per liter
Standard Deviation 61.23
|
-18.05 Micromole per liter
Standard Deviation 82.41
|
5.69 Micromole per liter
Standard Deviation 50.16
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Uric acid, Day 35
|
-8.63 Micromole per liter
Standard Deviation 57.75
|
-4.51 Micromole per liter
Standard Deviation 56.60
|
12.03 Micromole per liter
Standard Deviation 59.59
|
-2.45 Micromole per liter
Standard Deviation 57.67
|
2.30 Micromole per liter
Standard Deviation 55.55
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Direct bilirubin, Day 8
|
0.26 Micromole per liter
Standard Deviation 0.78
|
0.27 Micromole per liter
Standard Deviation 0.65
|
0.13 Micromole per liter
Standard Deviation 0.55
|
0.30 Micromole per liter
Standard Deviation 0.88
|
-0.05 Micromole per liter
Standard Deviation 0.88
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Direct bilirubin, Day 15
|
0.19 Micromole per liter
Standard Deviation 0.60
|
0.13 Micromole per liter
Standard Deviation 0.52
|
-0.06 Micromole per liter
Standard Deviation 0.44
|
0.43 Micromole per liter
Standard Deviation 0.90
|
0.11 Micromole per liter
Standard Deviation 0.68
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Direct bilirubin, Day 22
|
0.10 Micromole per liter
Standard Deviation 0.70
|
0.08 Micromole per liter
Standard Deviation 0.35
|
0.03 Micromole per liter
Standard Deviation 0.74
|
0.21 Micromole per liter
Standard Deviation 0.58
|
0.19 Micromole per liter
Standard Deviation 0.70
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Direct bilirubin, Day 28
|
0.07 Micromole per liter
Standard Deviation 0.38
|
0.19 Micromole per liter
Standard Deviation 0.74
|
-0.11 Micromole per liter
Standard Deviation 0.50
|
0.26 Micromole per liter
Standard Deviation 0.85
|
-0.08 Micromole per liter
Standard Deviation 0.59
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Direct bilirubin, Day 35
|
-0.06 Micromole per liter
Standard Deviation 0.60
|
-0.05 Micromole per liter
Standard Deviation 0.32
|
-0.25 Micromole per liter
Standard Deviation 0.67
|
0.00 Micromole per liter
Standard Deviation 0.53
|
-0.06 Micromole per liter
Standard Deviation 0.92
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Indirect bilirubin, Day 8
|
1.06 Micromole per liter
Standard Deviation 3.31
|
1.49 Micromole per liter
Standard Deviation 3.52
|
0.91 Micromole per liter
Standard Deviation 3.32
|
1.22 Micromole per liter
Standard Deviation 4.36
|
-0.30 Micromole per liter
Standard Deviation 3.02
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Indirect bilirubin, Day 15
|
0.71 Micromole per liter
Standard Deviation 4.03
|
0.56 Micromole per liter
Standard Deviation 2.55
|
0.52 Micromole per liter
Standard Deviation 3.37
|
1.22 Micromole per liter
Standard Deviation 2.90
|
0.31 Micromole per liter
Standard Deviation 2.47
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Indirect bilirubin, Day 22
|
0.61 Micromole per liter
Standard Deviation 3.04
|
0.62 Micromole per liter
Standard Deviation 3.27
|
1.09 Micromole per liter
Standard Deviation 3.37
|
0.39 Micromole per liter
Standard Deviation 2.69
|
0.70 Micromole per liter
Standard Deviation 3.44
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Indirect bilirubin, Day 28
|
0.04 Micromole per liter
Standard Deviation 3.21
|
0.38 Micromole per liter
Standard Deviation 2.69
|
-0.36 Micromole per liter
Standard Deviation 2.68
|
-0.37 Micromole per liter
Standard Deviation 3.53
|
-0.58 Micromole per liter
Standard Deviation 3.59
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Indirect bilirubin, Day 35
|
-0.38 Micromole per liter
Standard Deviation 3.56
|
-0.08 Micromole per liter
Standard Deviation 2.95
|
-1.63 Micromole per liter
Standard Deviation 3.90
|
-1.24 Micromole per liter
Standard Deviation 2.78
|
-0.38 Micromole per liter
Standard Deviation 3.37
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Serum creatinine, Day 8
|
1.68 Micromole per liter
Standard Deviation 8.98
|
4.27 Micromole per liter
Standard Deviation 8.20
|
5.26 Micromole per liter
Standard Deviation 9.20
|
7.15 Micromole per liter
Standard Deviation 10.89
|
0.31 Micromole per liter
Standard Deviation 6.78
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Serum creatinine, Day 15
|
1.00 Micromole per liter
Standard Deviation 8.91
|
2.21 Micromole per liter
Standard Deviation 6.97
|
2.45 Micromole per liter
Standard Deviation 8.30
|
5.83 Micromole per liter
Standard Deviation 10.15
|
-1.05 Micromole per liter
Standard Deviation 6.80
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Serum creatinine, Day 22
|
1.13 Micromole per liter
Standard Deviation 10.01
|
2.57 Micromole per liter
Standard Deviation 7.17
|
2.61 Micromole per liter
Standard Deviation 9.49
|
5.50 Micromole per liter
Standard Deviation 8.23
|
-0.74 Micromole per liter
Standard Deviation 6.97
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Serum creatinine, Day 28
|
1.09 Micromole per liter
Standard Deviation 9.24
|
1.85 Micromole per liter
Standard Deviation 9.47
|
1.03 Micromole per liter
Standard Deviation 6.89
|
2.78 Micromole per liter
Standard Deviation 9.16
|
-1.12 Micromole per liter
Standard Deviation 7.38
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Serum creatinine, Day 35
|
0.07 Micromole per liter
Standard Deviation 9.91
|
0.93 Micromole per liter
Standard Deviation 6.87
|
-1.46 Micromole per liter
Standard Deviation 6.89
|
0.40 Micromole per liter
Standard Deviation 8.00
|
-0.75 Micromole per liter
Standard Deviation 7.50
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Total bilirubin, Day 8
|
1.24 Micromole per liter
Standard Deviation 3.73
|
1.77 Micromole per liter
Standard Deviation 4.13
|
1.39 Micromole per liter
Standard Deviation 3.78
|
2.08 Micromole per liter
Standard Deviation 6.16
|
-0.49 Micromole per liter
Standard Deviation 3.72
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Total bilirubin, Day 15
|
1.25 Micromole per liter
Standard Deviation 4.16
|
0.73 Micromole per liter
Standard Deviation 2.95
|
1.68 Micromole per liter
Standard Deviation 4.87
|
1.95 Micromole per liter
Standard Deviation 4.42
|
0.44 Micromole per liter
Standard Deviation 3.16
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Total bilirubin, Day 22
|
1.05 Micromole per liter
Standard Deviation 3.38
|
0.83 Micromole per liter
Standard Deviation 3.41
|
1.76 Micromole per liter
Standard Deviation 3.97
|
1.21 Micromole per liter
Standard Deviation 4.57
|
0.98 Micromole per liter
Standard Deviation 3.75
|
|
Change From Baseline in Chemistry Parameter of Direct Bilirubin, Indirect Bilirubin, Serum Creatinine, Total Bilirubin and Uric Acid Over Time
Total bilirubin, Day 28
|
0.17 Micromole per liter
Standard Deviation 3.46
|
0.90 Micromole per liter
Standard Deviation 3.39
|
0.30 Micromole per liter
Standard Deviation 4.22
|
-0.03 Micromole per liter
Standard Deviation 5.22
|
-0.64 Micromole per liter
Standard Deviation 4.17
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
HDL, Day 8
|
0.01 mmol per liter
Standard Deviation 0.19
|
0.02 mmol per liter
Standard Deviation 0.19
|
0.05 mmol per liter
Standard Deviation 0.18
|
-0.03 mmol per liter
Standard Deviation 0.17
|
-0.02 mmol per liter
Standard Deviation 0.14
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
HDL, Day 15
|
0.01 mmol per liter
Standard Deviation 0.17
|
-0.01 mmol per liter
Standard Deviation 0.20
|
0.08 mmol per liter
Standard Deviation 0.21
|
-0.03 mmol per liter
Standard Deviation 0.16
|
-0.02 mmol per liter
Standard Deviation 0.21
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
HDL, Day 22
|
0.02 mmol per liter
Standard Deviation 0.23
|
0.02 mmol per liter
Standard Deviation 0.19
|
0.05 mmol per liter
Standard Deviation 0.14
|
-0.04 mmol per liter
Standard Deviation 0.18
|
-0.03 mmol per liter
Standard Deviation 0.21
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
HDL, Day 28
|
-0.02 mmol per liter
Standard Deviation 0.20
|
-0.04 mmol per liter
Standard Deviation 0.20
|
0.01 mmol per liter
Standard Deviation 0.18
|
-0.05 mmol per liter
Standard Deviation 0.20
|
-0.04 mmol per liter
Standard Deviation 0.24
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
HDL, Day 35
|
0.00 mmol per liter
Standard Deviation 0.17
|
-0.01 mmol per liter
Standard Deviation 0.22
|
0.05 mmol per liter
Standard Deviation 0.15
|
-0.01 mmol per liter
Standard Deviation 0.18
|
-0.03 mmol per liter
Standard Deviation 0.22
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
LDL, Day 8
|
-0.27 mmol per liter
Standard Deviation 0.76
|
-0.16 mmol per liter
Standard Deviation 0.57
|
-0.19 mmol per liter
Standard Deviation 0.45
|
-0.20 mmol per liter
Standard Deviation 0.51
|
-0.10 mmol per liter
Standard Deviation 0.57
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
LDL, Day 15
|
-0.26 mmol per liter
Standard Deviation 0.83
|
-0.23 mmol per liter
Standard Deviation 0.76
|
-0.22 mmol per liter
Standard Deviation 0.61
|
-0.26 mmol per liter
Standard Deviation 0.59
|
-0.07 mmol per liter
Standard Deviation 0.53
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
LDL, Day 22
|
-0.34 mmol per liter
Standard Deviation 0.67
|
-0.14 mmol per liter
Standard Deviation 0.88
|
-0.23 mmol per liter
Standard Deviation 0.52
|
-0.17 mmol per liter
Standard Deviation 0.74
|
-0.02 mmol per liter
Standard Deviation 0.68
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
LDL, Day 28
|
-0.17 mmol per liter
Standard Deviation 0.77
|
-0.29 mmol per liter
Standard Deviation 0.75
|
-0.28 mmol per liter
Standard Deviation 0.59
|
-0.22 mmol per liter
Standard Deviation 0.86
|
-0.07 mmol per liter
Standard Deviation 0.69
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
LDL, Day 35
|
-0.30 mmol per liter
Standard Deviation 0.83
|
-0.14 mmol per liter
Standard Deviation 0.77
|
-0.15 mmol per liter
Standard Deviation 0.50
|
-0.07 mmol per liter
Standard Deviation 0.86
|
-0.08 mmol per liter
Standard Deviation 0.71
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Total cholesterol, Day 8
|
-0.33 mmol per liter
Standard Deviation 0.89
|
-0.27 mmol per liter
Standard Deviation 0.72
|
-0.38 mmol per liter
Standard Deviation 0.50
|
-0.27 mmol per liter
Standard Deviation 0.59
|
-0.16 mmol per liter
Standard Deviation 0.62
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Total cholesterol, Day 15
|
-0.38 mmol per liter
Standard Deviation 0.97
|
-0.27 mmol per liter
Standard Deviation 0.98
|
-0.35 mmol per liter
Standard Deviation 0.82
|
-0.27 mmol per liter
Standard Deviation 0.72
|
-0.09 mmol per liter
Standard Deviation 0.71
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Total cholesterol, Day 22
|
-0.46 mmol per liter
Standard Deviation 0.81
|
-0.16 mmol per liter
Standard Deviation 1.06
|
-0.49 mmol per liter
Standard Deviation 0.81
|
-0.20 mmol per liter
Standard Deviation 0.88
|
-0.09 mmol per liter
Standard Deviation 0.92
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Total cholesterol, Day 28
|
-0.23 mmol per liter
Standard Deviation 0.93
|
-0.25 mmol per liter
Standard Deviation 0.89
|
-0.55 mmol per liter
Standard Deviation 0.81
|
-0.23 mmol per liter
Standard Deviation 0.92
|
-0.15 mmol per liter
Standard Deviation 0.97
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Total cholesterol, Day 35
|
-0.47 mmol per liter
Standard Deviation 0.88
|
-0.22 mmol per liter
Standard Deviation 1.07
|
-0.41 mmol per liter
Standard Deviation 0.93
|
-0.11 mmol per liter
Standard Deviation 1.04
|
-0.11 mmol per liter
Standard Deviation 0.98
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Triglycerides, Day 8
|
-0.14 mmol per liter
Standard Deviation 1.12
|
-0.22 mmol per liter
Standard Deviation 0.76
|
-0.66 mmol per liter
Standard Deviation 1.33
|
-0.13 mmol per liter
Standard Deviation 0.63
|
-0.15 mmol per liter
Standard Deviation 0.93
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Triglycerides, Day 15
|
-0.34 mmol per liter
Standard Deviation 1.36
|
0.02 mmol per liter
Standard Deviation 1.23
|
-0.50 mmol per liter
Standard Deviation 0.97
|
0.07 mmol per liter
Standard Deviation 1.02
|
0.04 mmol per liter
Standard Deviation 1.05
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Triglycerides, Day 22
|
-0.36 mmol per liter
Standard Deviation 1.30
|
-0.02 mmol per liter
Standard Deviation 0.97
|
-0.83 mmol per liter
Standard Deviation 1.89
|
0.08 mmol per liter
Standard Deviation 1.32
|
-0.08 mmol per liter
Standard Deviation 1.03
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Triglycerides, Day 28
|
-0.09 mmol per liter
Standard Deviation 1.60
|
0.22 mmol per liter
Standard Deviation 0.95
|
-0.75 mmol per liter
Standard Deviation 1.91
|
0.03 mmol per liter
Standard Deviation 1.51
|
-0.08 mmol per liter
Standard Deviation 1.06
|
|
Change From Baseline in Chemistry Parameter of Lipid Profile Over Time
Triglycerides, Day 35
|
-0.30 mmol per liter
Standard Deviation 0.81
|
-0.32 mmol per liter
Standard Deviation 3.03
|
-0.90 mmol per liter
Standard Deviation 2.29
|
-0.19 mmol per liter
Standard Deviation 0.88
|
-0.02 mmol per liter
Standard Deviation 0.83
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Albumin, Day 8
|
0.80 Gram per liter
Standard Deviation 2.40
|
0.78 Gram per liter
Standard Deviation 2.72
|
0.64 Gram per liter
Standard Deviation 2.05
|
1.02 Gram per liter
Standard Deviation 1.93
|
0.29 Gram per liter
Standard Deviation 2.03
|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Albumin, Day 15
|
1.05 Gram per liter
Standard Deviation 2.39
|
0.29 Gram per liter
Standard Deviation 2.39
|
0.13 Gram per liter
Standard Deviation 2.24
|
0.53 Gram per liter
Standard Deviation 2.06
|
0.80 Gram per liter
Standard Deviation 2.44
|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Albumin, Day 22
|
0.82 Gram per liter
Standard Deviation 2.46
|
0.10 Gram per liter
Standard Deviation 2.34
|
0.55 Gram per liter
Standard Deviation 2.37
|
0.40 Gram per liter
Standard Deviation 2.02
|
0.67 Gram per liter
Standard Deviation 1.91
|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Albumin, Day 28
|
0.00 Gram per liter
Standard Deviation 2.45
|
-0.63 Gram per liter
Standard Deviation 2.79
|
-0.32 Gram per liter
Standard Deviation 2.24
|
-0.53 Gram per liter
Standard Deviation 2.40
|
0.45 Gram per liter
Standard Deviation 2.15
|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Albumin, Day 35
|
-0.07 Gram per liter
Standard Deviation 2.08
|
-0.17 Gram per liter
Standard Deviation 2.56
|
-0.16 Gram per liter
Standard Deviation 2.48
|
-0.21 Gram per liter
Standard Deviation 2.31
|
-0.02 Gram per liter
Standard Deviation 2.59
|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Total protein, Day 8
|
1.24 Gram per liter
Standard Deviation 4.39
|
0.23 Gram per liter
Standard Deviation 4.29
|
0.21 Gram per liter
Standard Deviation 3.15
|
1.24 Gram per liter
Standard Deviation 4.16
|
-0.24 Gram per liter
Standard Deviation 3.33
|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Total protein, Day 15
|
0.67 Gram per liter
Standard Deviation 4.68
|
0.63 Gram per liter
Standard Deviation 4.92
|
-1.24 Gram per liter
Standard Deviation 4.28
|
-0.03 Gram per liter
Standard Deviation 4.38
|
0.44 Gram per liter
Standard Deviation 4.43
|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Total protein, Day 22
|
1.29 Gram per liter
Standard Deviation 5.54
|
0.49 Gram per liter
Standard Deviation 4.90
|
0.18 Gram per liter
Standard Deviation 3.81
|
-0.03 Gram per liter
Standard Deviation 3.88
|
0.48 Gram per liter
Standard Deviation 3.21
|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Total protein, Day 28
|
0.06 Gram per liter
Standard Deviation 5.17
|
-1.10 Gram per liter
Standard Deviation 5.45
|
-0.63 Gram per liter
Standard Deviation 3.76
|
-1.49 Gram per liter
Standard Deviation 4.48
|
0.21 Gram per liter
Standard Deviation 3.76
|
|
Change From Baseline in Chemistry Parameter of Albumin and Total Protein Over Time
Total protein, Day 35
|
-0.61 Gram per liter
Standard Deviation 3.94
|
-0.07 Gram per liter
Standard Deviation 4.66
|
-0.95 Gram per liter
Standard Deviation 4.16
|
-1.57 Gram per liter
Standard Deviation 4.80
|
-0.05 Gram per liter
Standard Deviation 4.03
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Urinalysis Parameter of Specific Gravity Over Time
Day 8
|
-0.00 Ratio
Standard Deviation 0.01
|
0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
|
Change From Baseline in Urinalysis Parameter of Specific Gravity Over Time
Day 15
|
-0.00 Ratio
Standard Deviation 0.00
|
-0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
|
Change From Baseline in Urinalysis Parameter of Specific Gravity Over Time
Day 22
|
-0.00 Ratio
Standard Deviation 0.01
|
0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
|
Change From Baseline in Urinalysis Parameter of Specific Gravity Over Time
Day 28
|
-0.00 Ratio
Standard Deviation 0.01
|
0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
0.00 Ratio
Standard Deviation 0.01
|
0.00 Ratio
Standard Deviation 0.01
|
|
Change From Baseline in Urinalysis Parameter of Specific Gravity Over Time
Day 35
|
-0.00 Ratio
Standard Deviation 0.01
|
0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
-0.00 Ratio
Standard Deviation 0.01
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: Safety Analysis Set Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=43 Participants
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.
|
SRT2104 0.5 g/Day
n=44 Participants
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.
|
SRT2104 1.0 g/Day
n=42 Participants
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.
|
SRT2104 2.0 g/Day
n=43 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Urinalysis Parameter of pH Over Time
Day 8
|
-0.05 Points on scale
Standard Deviation 0.38
|
-0.02 Points on scale
Standard Deviation 0.35
|
0.00 Points on scale
Standard Deviation 0.43
|
0.10 Points on scale
Standard Deviation 0.51
|
0.05 Points on scale
Standard Deviation 0.34
|
|
Change From Baseline in Urinalysis Parameter of pH Over Time
Day 15
|
-0.04 Points on scale
Standard Deviation 0.45
|
-0.05 Points on scale
Standard Deviation 0.57
|
0.11 Points on scale
Standard Deviation 0.47
|
0.08 Points on scale
Standard Deviation 0.62
|
0.05 Points on scale
Standard Deviation 0.35
|
|
Change From Baseline in Urinalysis Parameter of pH Over Time
Day 22
|
-0.03 Points on scale
Standard Deviation 0.50
|
0.01 Points on scale
Standard Deviation 0.55
|
0.05 Points on scale
Standard Deviation 0.40
|
-0.03 Points on scale
Standard Deviation 0.48
|
0.14 Points on scale
Standard Deviation 0.41
|
|
Change From Baseline in Urinalysis Parameter of pH Over Time
Day 28
|
-0.09 Points on scale
Standard Deviation 0.43
|
0.00 Points on scale
Standard Deviation 0.59
|
0.03 Points on scale
Standard Deviation 0.37
|
0.04 Points on scale
Standard Deviation 0.63
|
0.28 Points on scale
Standard Deviation 0.66
|
|
Change From Baseline in Urinalysis Parameter of pH Over Time
Day 35
|
-0.15 Points on scale
Standard Deviation 0.37
|
-0.12 Points on scale
Standard Deviation 0.55
|
0.01 Points on scale
Standard Deviation 0.38
|
0.07 Points on scale
Standard Deviation 0.52
|
0.06 Points on scale
Standard Deviation 0.48
|
PRIMARY outcome
Timeframe: 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)Population: 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.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=44 Participants
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.
|
SRT2104 0.5 g/Day
n=42 Participants
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.
|
SRT2104 1.0 g/Day
n=43 Participants
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.
|
SRT2104 2.0 g/Day
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
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, AUC 0-t
|
2153.0075 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 1835.6039
|
2375.3150 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 2285.7123
|
2859.5465 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 2916.4783
|
—
|
1045.8420 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 978.3355
|
|
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 28, AUC 0-t
|
2731.6308 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 2337.0839
|
3109.8747 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 2948.2780
|
4380.2204 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 4476.9484
|
—
|
1549.6139 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 1450.1354
|
|
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, AUC 0-infinity
|
2797.6930 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 2287.3141
|
3080.6902 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 2532.8224
|
3837.1384 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 4078.6970
|
—
|
1564.4905 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 1119.3480
|
|
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 28, AUC 0-infinity
|
4634.3397 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 5387.2429
|
4960.3422 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 3914.0260
|
8159.4534 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 7592.2760
|
—
|
2289.6858 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 1876.6537
|
|
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 28, AUC 0-τ
|
2731.6231 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 2337.0919
|
3212.6640 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 2924.1860
|
4584.5679 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 4502.8752
|
—
|
1620.5989 Nanogram (ng)*hour/milliliter (mL)
Standard Deviation 1431.4150
|
PRIMARY outcome
Timeframe: 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)Population: PK Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=44 Participants
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.
|
SRT2104 0.5 g/Day
n=42 Participants
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.
|
SRT2104 1.0 g/Day
n=43 Participants
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.
|
SRT2104 2.0 g/Day
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Observed Maximum Plasma Concentration (Cmax) of SRT2104 at Day 1 and Day 28
Day 1
|
366.694 ng/mL
Standard Deviation 322.951
|
336.562 ng/mL
Standard Deviation 298.042
|
417.832 ng/mL
Standard Deviation 470.048
|
—
|
178.729 ng/mL
Standard Deviation 179.982
|
|
Observed Maximum Plasma Concentration (Cmax) of SRT2104 at Day 1 and Day 28
Day 28
|
329.973 ng/mL
Standard Deviation 266.174
|
375.395 ng/mL
Standard Deviation 333.188
|
433.650 ng/mL
Standard Deviation 461.441
|
—
|
185.418 ng/mL
Standard Deviation 162.500
|
PRIMARY outcome
Timeframe: 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)Population: PK Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=44 Participants
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.
|
SRT2104 0.5 g/Day
n=42 Participants
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.
|
SRT2104 1.0 g/Day
n=43 Participants
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.
|
SRT2104 2.0 g/Day
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Time to Cmax (Tmax) at Day 1 and Day 28
Day 1
|
3.000 hour
Interval 1.0 to 24.0
|
3.000 hour
Interval 2.0 to 8.0
|
4.000 hour
Interval 0.25 to 12.0
|
—
|
3.000 hour
Interval 2.0 to 8.0
|
|
Time to Cmax (Tmax) at Day 1 and Day 28
Day 28
|
3.000 hour
Interval 0.0 to 12.0
|
3.000 hour
Interval 0.0 to 24.0
|
3.000 hour
Interval 0.0 to 12.0
|
—
|
3.000 hour
Interval 0.0 to 24.0
|
PRIMARY outcome
Timeframe: 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)Population: PK Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=44 Participants
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.
|
SRT2104 0.5 g/Day
n=42 Participants
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.
|
SRT2104 1.0 g/Day
n=43 Participants
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.
|
SRT2104 2.0 g/Day
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Terminal Elimination Half Life (T1/2) of SRT2104 at Day 1 and Day 28
Day 1
|
12.1669 hour
Interval 6.1089 to 40.6904
|
13.3434 hour
Interval 6.4721 to 54.7509
|
9.7846 hour
Interval 3.81 to 24.2013
|
—
|
13.4184 hour
Interval 4.0113 to 33.0069
|
|
Terminal Elimination Half Life (T1/2) of SRT2104 at Day 1 and Day 28
Day 28
|
20.3500 hour
Interval 7.3262 to 66.2388
|
18.9258 hour
Interval 7.6823 to 42.6557
|
17.4548 hour
Interval 9.0649 to 42.0806
|
—
|
18.0115 hour
Interval 7.1058 to 31.3329
|
PRIMARY outcome
Timeframe: 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)Population: PK Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=44 Participants
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.
|
SRT2104 0.5 g/Day
n=42 Participants
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.
|
SRT2104 1.0 g/Day
n=43 Participants
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.
|
SRT2104 2.0 g/Day
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Apparent Total Clearance of SRT2104 From Plasma After Oral Administration (CL/F) on Day 1 and Day 28
Day 1
|
621.3930 Liter/hour
Standard Deviation 948.1533
|
1582.0131 Liter/hour
Standard Deviation 2707.3466
|
2181.8596 Liter/hour
Standard Deviation 2959.1044
|
—
|
494.0236 Liter/hour
Standard Deviation 625.5532
|
|
Apparent Total Clearance of SRT2104 From Plasma After Oral Administration (CL/F) on Day 1 and Day 28
Day 28
|
956.6848 Liter/hour
Standard Deviation 2117.3623
|
1420.2734 Liter/hour
Standard Deviation 2128.7769
|
1887.2455 Liter/hour
Standard Deviation 2883.3080
|
—
|
631.5519 Liter/hour
Standard Deviation 900.3648
|
PRIMARY outcome
Timeframe: 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)Population: PK Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=44 Participants
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.
|
SRT2104 0.5 g/Day
n=42 Participants
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.
|
SRT2104 1.0 g/Day
n=43 Participants
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.
|
SRT2104 2.0 g/Day
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Apparent Volume of Distribution After Oral Administration (Vd/F) at Day 1 and Day 28
Day 1
|
15767.2219 mL/kg
Standard Deviation 29059.7570
|
38320.97415 mL/kg
Standard Deviation 77339.06047
|
32262.5089 mL/kg
Standard Deviation 45180.0346
|
—
|
12921.7880 mL/kg
Standard Deviation 19802.8598
|
|
Apparent Volume of Distribution After Oral Administration (Vd/F) at Day 1 and Day 28
Day 28
|
48475.7739 mL/kg
Standard Deviation 150725.4900
|
56531.7676 mL/kg
Standard Deviation 108327.3925
|
51594.5474 mL/kg
Standard Deviation 93165.0710
|
—
|
17509.8071 mL/kg
Standard Deviation 27627.2504
|
SECONDARY outcome
Timeframe: Up to Day 35Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Mean Fasting Plasma Glucose (FPG) Levels Over Time
Day 8
|
10.33 mmol per liter
Standard Deviation 2.30
|
11.10 mmol per liter
Standard Deviation 2.33
|
10.67 mmol per liter
Standard Deviation 2.19
|
10.37 mmol per liter
Standard Deviation 2.81
|
10.46 mmol per liter
Standard Deviation 2.60
|
|
Mean Fasting Plasma Glucose (FPG) Levels Over Time
Day 15
|
10.52 mmol per liter
Standard Deviation 2.40
|
10.51 mmol per liter
Standard Deviation 2.39
|
10.37 mmol per liter
Standard Deviation 2.30
|
10.41 mmol per liter
Standard Deviation 2.81
|
10.08 mmol per liter
Standard Deviation 2.46
|
|
Mean Fasting Plasma Glucose (FPG) Levels Over Time
Day 22
|
10.31 mmol per liter
Standard Deviation 2.66
|
11.24 mmol per liter
Standard Deviation 2.17
|
10.59 mmol per liter
Standard Deviation 2.35
|
10.56 mmol per liter
Standard Deviation 2.84
|
10.03 mmol per liter
Standard Deviation 2.03
|
|
Mean Fasting Plasma Glucose (FPG) Levels Over Time
Day 28
|
10.21 mmol per liter
Standard Deviation 2.12
|
10.49 mmol per liter
Standard Deviation 2.22
|
10.32 mmol per liter
Standard Deviation 2.16
|
10.05 mmol per liter
Standard Deviation 2.38
|
9.60 mmol per liter
Standard Deviation 2.02
|
|
Mean Fasting Plasma Glucose (FPG) Levels Over Time
Day 35
|
10.10 mmol per liter
Standard Deviation 2.21
|
9.92 mmol per liter
Standard Deviation 2.04
|
9.51 mmol per liter
Standard Deviation 2.62
|
9.03 mmol per liter
Standard Deviation 1.98
|
10.10 mmol per liter
Standard Deviation 2.41
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in FPG Levels Over Time
Day 8
|
-1.00 mmol per liter
Standard Deviation 3.23
|
0.16 mmol per liter
Standard Deviation 2.06
|
-0.41 mmol per liter
Standard Deviation 2.77
|
0.17 mmol per liter
Standard Deviation 2.05
|
-0.30 mmol per liter
Standard Deviation 2.20
|
|
Change From Baseline in FPG Levels Over Time
Day 15
|
-0.91 mmol per liter
Standard Deviation 2.61
|
-0.41 mmol per liter
Standard Deviation 2.35
|
-0.64 mmol per liter
Standard Deviation 2.78
|
0.17 mmol per liter
Standard Deviation 2.72
|
-0.72 mmol per liter
Standard Deviation 2.45
|
|
Change From Baseline in FPG Levels Over Time
Day 22
|
-1.06 mmol per liter
Standard Deviation 3.63
|
0.28 mmol per liter
Standard Deviation 2.79
|
-0.47 mmol per liter
Standard Deviation 2.90
|
0.40 mmol per liter
Standard Deviation 2.71
|
-0.74 mmol per liter
Standard Deviation 2.48
|
|
Change From Baseline in FPG Levels Over Time
Day 28
|
-1.11 mmol per liter
Standard Deviation 3.45
|
-0.52 mmol per liter
Standard Deviation 2.60
|
-0.97 mmol per liter
Standard Deviation 2.83
|
-0.15 mmol per liter
Standard Deviation 2.38
|
-1.17 mmol per liter
Standard Deviation 2.42
|
|
Change From Baseline in FPG Levels Over Time
Day 35
|
-0.94 mmol per liter
Standard Deviation 2.47
|
-1.24 mmol per liter
Standard Deviation 3.07
|
-1.52 mmol per liter
Standard Deviation 3.29
|
-1.14 mmol per liter
Standard Deviation 2.37
|
-0.73 mmol per liter
Standard Deviation 2.70
|
SECONDARY outcome
Timeframe: Up to Day 35Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Mean Fasting Plasma Insulin (FPI) Levels Over Time
Day 8
|
92.3 mmol per liter
Standard Deviation 95.57
|
83.8 mmol per liter
Standard Deviation 52.19
|
74.5 mmol per liter
Standard Deviation 61.77
|
74.4 mmol per liter
Standard Deviation 51.36
|
89.9 mmol per liter
Standard Deviation 59.63
|
|
Mean Fasting Plasma Insulin (FPI) Levels Over Time
Day 15
|
78.4 mmol per liter
Standard Deviation 93.50
|
80.4 mmol per liter
Standard Deviation 45.86
|
80.5 mmol per liter
Standard Deviation 76.39
|
79.3 mmol per liter
Standard Deviation 89.05
|
90.0 mmol per liter
Standard Deviation 70.89
|
|
Mean Fasting Plasma Insulin (FPI) Levels Over Time
Day 22
|
74.3 mmol per liter
Standard Deviation 93.51
|
81.8 mmol per liter
Standard Deviation 47.79
|
78.8 mmol per liter
Standard Deviation 65.46
|
76.8 mmol per liter
Standard Deviation 57.34
|
98.7 mmol per liter
Standard Deviation 98.55
|
|
Mean Fasting Plasma Insulin (FPI) Levels Over Time
Day 28
|
91.7 mmol per liter
Standard Deviation 118.05
|
63.7 mmol per liter
Standard Deviation 44.87
|
63.3 mmol per liter
Standard Deviation 55.69
|
89.2 mmol per liter
Standard Deviation 134.56
|
82.4 mmol per liter
Standard Deviation 56.91
|
|
Mean Fasting Plasma Insulin (FPI) Levels Over Time
Day 35
|
110.5 mmol per liter
Standard Deviation 157.53
|
87.1 mmol per liter
Standard Deviation 56.22
|
84.0 mmol per liter
Standard Deviation 78.95
|
115.3 mmol per liter
Standard Deviation 213.37
|
101.6 mmol per liter
Standard Deviation 70.49
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and up to Day 35Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in FPI Over Time
Day 8
|
12.2 mmol per liter
Standard Deviation 80.20
|
12.3 mmol per liter
Standard Deviation 49.91
|
12.9 mmol per liter
Standard Deviation 63.97
|
4.7 mmol per liter
Standard Deviation 37.72
|
7.2 mmol per liter
Standard Deviation 66.75
|
|
Change From Baseline in FPI Over Time
Day 15
|
-6.5 mmol per liter
Standard Deviation 48.51
|
8.1 mmol per liter
Standard Deviation 45.43
|
18.8 mmol per liter
Standard Deviation 88.06
|
8.3 mmol per liter
Standard Deviation 96.60
|
10.8 mmol per liter
Standard Deviation 77.13
|
|
Change From Baseline in FPI Over Time
Day 22
|
-4.6 mmol per liter
Standard Deviation 55.62
|
10.6 mmol per liter
Standard Deviation 56.34
|
20.2 mmol per liter
Standard Deviation 75.69
|
0.3 mmol per liter
Standard Deviation 49.95
|
17.6 mmol per liter
Standard Deviation 90.89
|
|
Change From Baseline in FPI Over Time
Day 28
|
8.9 mmol per liter
Standard Deviation 95.04
|
-6.9 mmol per liter
Standard Deviation 41.45
|
4.1 mmol per liter
Standard Deviation 57.16
|
15.2 mmol per liter
Standard Deviation 138.79
|
1.0 mmol per liter
Standard Deviation 51.66
|
|
Change From Baseline in FPI Over Time
Day 35
|
30.7 mmol per liter
Standard Deviation 103.55
|
13.7 mmol per liter
Standard Deviation 47.92
|
22.3 mmol per liter
Standard Deviation 79.42
|
48.0 mmol per liter
Standard Deviation 216.64
|
20.4 mmol per liter
Standard Deviation 80.92
|
SECONDARY outcome
Timeframe: Day 28Population: ITT Population. Only those participants available at the specified time points were analyzed.
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).
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Mean Post-prandial Glucose (PPG) and Post-prandial Insulin (PPI) Levels at Day 28
PPG, 30 minutes
|
12.95 mmol per liter
Standard Deviation 2.66
|
13.58 mmol per liter
Standard Deviation 3.05
|
13.12 mmol per liter
Standard Deviation 2.90
|
11.41 mmol per liter
Standard Deviation 2.77
|
12.91 mmol per liter
Standard Deviation 2.94
|
|
Mean Post-prandial Glucose (PPG) and Post-prandial Insulin (PPI) Levels at Day 28
PPG, 60 minutes
|
14.05 mmol per liter
Standard Deviation 3.57
|
15.44 mmol per liter
Standard Deviation 3.05
|
14.77 mmol per liter
Standard Deviation 3.16
|
13.08 mmol per liter
Standard Deviation 3.70
|
14.05 mmol per liter
Standard Deviation 3.13
|
|
Mean Post-prandial Glucose (PPG) and Post-prandial Insulin (PPI) Levels at Day 28
PPG, 2 hour
|
13.15 mmol per liter
Standard Deviation 3.55
|
14.74 mmol per liter
Standard Deviation 3.15
|
13.90 mmol per liter
Standard Deviation 3.60
|
13.61 mmol per liter
Standard Deviation 4.43
|
13.16 mmol per liter
Standard Deviation 4.26
|
|
Mean Post-prandial Glucose (PPG) and Post-prandial Insulin (PPI) Levels at Day 28
PPI, 30 minutes
|
217.2 mmol per liter
Standard Deviation 198.91
|
188.3 mmol per liter
Standard Deviation 172.53
|
160.2 mmol per liter
Standard Deviation 153.46
|
163.0 mmol per liter
Standard Deviation 179.83
|
237.6 mmol per liter
Standard Deviation 222.95
|
|
Mean Post-prandial Glucose (PPG) and Post-prandial Insulin (PPI) Levels at Day 28
PPI, 60 minutes
|
285.4 mmol per liter
Standard Deviation 339.90
|
223.0 mmol per liter
Standard Deviation 167.72
|
189.2 mmol per liter
Standard Deviation 145.83
|
226.6 mmol per liter
Standard Deviation 200.82
|
298.1 mmol per liter
Standard Deviation 232.43
|
|
Mean Post-prandial Glucose (PPG) and Post-prandial Insulin (PPI) Levels at Day 28
PPI, 2 hour
|
215.0 mmol per liter
Standard Deviation 309.78
|
192.5 mmol per liter
Standard Deviation 132.93
|
183.8 mmol per liter
Standard Deviation 160.20
|
206.4 mmol per liter
Standard Deviation 202.40
|
224.4 mmol per liter
Standard Deviation 129.69
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Day 28Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in PPG and PPI Levels at Day 28
PPG, 30 minutes
|
2.82 mmol per liter
Standard Deviation 2.40
|
3.40 mmol per liter
Standard Deviation 2.52
|
3.14 mmol per liter
Standard Deviation 1.75
|
2.00 mmol per liter
Standard Deviation 2.17
|
3.38 mmol per liter
Standard Deviation 2.85
|
|
Change From Baseline in PPG and PPI Levels at Day 28
PPG, 60 minutes
|
3.92 mmol per liter
Standard Deviation 3.55
|
5.12 mmol per liter
Standard Deviation 2.57
|
4.74 mmol per liter
Standard Deviation 2.34
|
3.68 mmol per liter
Standard Deviation 3.08
|
4.53 mmol per liter
Standard Deviation 2.86
|
|
Change From Baseline in PPG and PPI Levels at Day 28
PPG, 2 hour
|
2.93 mmol per liter
Standard Deviation 3.33
|
4.23 mmol per liter
Standard Deviation 2.88
|
3.66 mmol per liter
Standard Deviation 2.54
|
3.47 mmol per liter
Standard Deviation 3.44
|
3.56 mmol per liter
Standard Deviation 3.37
|
|
Change From Baseline in PPG and PPI Levels at Day 28
PPI, 30 minutes
|
108.7 mmol per liter
Standard Deviation 136.13
|
119.2 mmol per liter
Standard Deviation 157.32
|
94.9 mmol per liter
Standard Deviation 109.96
|
57.4 mmol per liter
Standard Deviation 73.07
|
162.4 mmol per liter
Standard Deviation 204.29
|
|
Change From Baseline in PPG and PPI Levels at Day 28
PPI, 60 minutes
|
176.9 mmol per liter
Standard Deviation 278.91
|
153.9 mmol per liter
Standard Deviation 146.74
|
128.4 mmol per liter
Standard Deviation 105.95
|
121.0 mmol per liter
Standard Deviation 95.22
|
222.9 mmol per liter
Standard Deviation 206.99
|
|
Change From Baseline in PPG and PPI Levels at Day 28
PPI, 2 hour
|
123.3 mmol per liter
Standard Deviation 253.84
|
128.7 mmol per liter
Standard Deviation 106.87
|
120.5 mmol per liter
Standard Deviation 129.95
|
117.3 mmol per liter
Standard Deviation 127.26
|
142.0 mmol per liter
Standard Deviation 113.58
|
SECONDARY outcome
Timeframe: Day 28Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=36 Participants
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.
|
SRT2104 0.5 g/Day
n=42 Participants
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.
|
SRT2104 1.0 g/Day
n=40 Participants
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.
|
SRT2104 2.0 g/Day
n=40 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Mean Glycosylated Hemoglobin A (HbA1c) Levels on Day 28
|
8.66 Percentage of HbA1c
Standard Deviation 1.00
|
8.64 Percentage of HbA1c
Standard Deviation 0.93
|
8.54 Percentage of HbA1c
Standard Deviation 1.16
|
8.29 Percentage of HbA1c
Standard Deviation 0.90
|
8.18 Percentage of HbA1c
Standard Deviation 0.95
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Day 28Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=35 Participants
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.
|
SRT2104 0.5 g/Day
n=42 Participants
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.
|
SRT2104 1.0 g/Day
n=38 Participants
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.
|
SRT2104 2.0 g/Day
n=40 Participants
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.
|
Placebo
n=43 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in HbA1c Levels at Day 28
|
-0.23 Percentage of HbA1c
Standard Deviation 0.68
|
-0.05 Percentage of HbA1c
Standard Deviation 0.52
|
0.01 Percentage of HbA1c
Standard Deviation 0.78
|
-0.10 Percentage of HbA1c
Standard Deviation 0.71
|
-0.31 Percentage of HbA1c
Standard Deviation 0.55
|
SECONDARY outcome
Timeframe: Day 1 (30 minutes, 60 minutes and 2 hour) and Day 28 (30 minutes, 60 minutes and 2 hour)Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=31 Participants
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.
|
SRT2104 0.5 g/Day
n=32 Participants
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.
|
SRT2104 1.0 g/Day
n=31 Participants
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.
|
SRT2104 2.0 g/Day
n=30 Participants
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.
|
Placebo
n=30 Participants
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.
|
|---|---|---|---|---|---|
|
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, AUC 0-1, PPG
|
14.08 mmol*hour per liter
Standard Deviation 3.40
|
14.28 mmol*hour per liter
Standard Deviation 3.50
|
14.43 mmol*hour per liter
Standard Deviation 4.18
|
12.68 mmol*hour per liter
Standard Deviation 2.73
|
13.10 mmol*hour per liter
Standard Deviation 2.69
|
|
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 28, AUC 0-1, PPG
|
12.52 mmol*hour per liter
Standard Deviation 2.41
|
13.25 mmol*hour per liter
Standard Deviation 2.58
|
12.92 mmol*hour per liter
Standard Deviation 2.27
|
11.33 mmol*hour per liter
Standard Deviation 2.63
|
12.35 mmol*hour per liter
Standard Deviation 2.45
|
|
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, AUC 0-2, PPG
|
29.35 mmol*hour per liter
Standard Deviation 7.64
|
29.87 mmol*hour per liter
Standard Deviation 7.20
|
29.95 mmol*hour per liter
Standard Deviation 9.34
|
26.07 mmol*hour per liter
Standard Deviation 5.99
|
27.39 mmol*hour per liter
Standard Deviation 5.72
|
|
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 28, AUC 0-2, PPG
|
25.98 mmol*hour per liter
Standard Deviation 5.64
|
28.30 mmol*hour per liter
Standard Deviation 5.51
|
27.01 mmol*hour per liter
Standard Deviation 5.11
|
24.14 mmol*hour per liter
Standard Deviation 6.40
|
25.89 mmol*hour per liter
Standard Deviation 5.84
|
|
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, AUC 0-1, PPI
|
211.1 mmol*hour per liter
Standard Deviation 245.53
|
176.6 mmol*hour per liter
Standard Deviation 105.51
|
168.3 mmol*hour per liter
Standard Deviation 123.33
|
186.0 mmol*hour per liter
Standard Deviation 92.55
|
192.4 mmol*hour per liter
Standard Deviation 121.08
|
|
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 28, AUC 0-1, PPI
|
207.1 mmol*hour per liter
Standard Deviation 202.43
|
168.1 mmol*hour per liter
Standard Deviation 135.71
|
138.8 mmol*hour per liter
Standard Deviation 120.34
|
164.6 mmol*hour per liter
Standard Deviation 175.64
|
212.1 mmol*hour per liter
Standard Deviation 176.25
|
|
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, AUC 0-2, PPI
|
478.8 mmol*hour per liter
Standard Deviation 584.46
|
418.4 mmol*hour per liter
Standard Deviation 251.25
|
377.6 mmol*hour per liter
Standard Deviation 297.27
|
385.8 mmol*hour per liter
Standard Deviation 167.81
|
423.8 mmol*hour per liter
Standard Deviation 289.68
|
|
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 28, AUC 0-2, PPI
|
477.7 mmol*hour per liter
Standard Deviation 538.49
|
394.5 mmol*hour per liter
Standard Deviation 276.65
|
334.7 mmol*hour per liter
Standard Deviation 256.51
|
381.3 mmol*hour per liter
Standard Deviation 378.70
|
444.8 mmol*hour per liter
Standard Deviation 332.82
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: ITT Population.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Mean Fructosamine Levels at Day 1 and Day 28
Day 1
|
320.38 mmol/L
Standard Deviation 49.20
|
319.82 mmol/L
Standard Deviation 56.73
|
328.44 mmol/L
Standard Deviation 62.90
|
296.00 mmol/L
Standard Deviation 41.86
|
320.07 mmol/L
Standard Deviation 61.28
|
|
Mean Fructosamine Levels at Day 1 and Day 28
Day 28
|
315.97 mmol/L
Standard Deviation 60.46
|
330.15 mmol/L
Standard Deviation 61.32
|
318.63 mmol/L
Standard Deviation 50.90
|
285.28 mmol/L
Standard Deviation 57.45
|
305.70 mmol/L
Standard Deviation 56.04
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Day 28Population: ITT Population.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in Fructosamine Levels at Day 28
|
-6.67 mmol per liter
Standard Deviation 40.27
|
9.76 mmol per liter
Standard Deviation 62.77
|
-4.68 mmol per liter
Standard Deviation 44.64
|
-2.14 mmol per liter
Standard Deviation 48.83
|
-14.37 mmol per liter
Standard Deviation 41.18
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Mean Homeostatic Model Assessment-insulin Resistance (HOMA-IR) at Day 1 and Day 28
Day 1
|
5.7 mU*mmol per liter^2
Standard Deviation 5.45
|
5.2 mU*mmol per liter^2
Standard Deviation 5.20
|
4.1 mU*mmol per liter^2
Standard Deviation 3.31
|
5.0 mU*mmol per liter^2
Standard Deviation 3.75
|
5.4 mU*mmol per liter^2
Standard Deviation 3.98
|
|
Mean Homeostatic Model Assessment-insulin Resistance (HOMA-IR) at Day 1 and Day 28
Day 28
|
5.9 mU*mmol per liter^2
Standard Deviation 7.28
|
3.9 mU*mmol per liter^2
Standard Deviation 2.55
|
4.0 mU*mmol per liter^2
Standard Deviation 3.66
|
5.9 mU*mmol per liter^2
Standard Deviation 10.10
|
4.9 mU*mmol per liter^2
Standard Deviation 3.56
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Day 28Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=34 Participants
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.
|
SRT2104 0.5 g/Day
n=39 Participants
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.
|
SRT2104 1.0 g/Day
n=35 Participants
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.
|
SRT2104 2.0 g/Day
n=35 Participants
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.
|
Placebo
n=41 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in HOMA-IR at Day 28
|
0.0 mU*mmol per liter^2
Standard Deviation 7.26
|
-0.9 mU*mmol per liter^2
Standard Deviation 3.47
|
-0.1 mU*mmol per liter^2
Standard Deviation 3.83
|
1.0 mU*mmol per liter^2
Standard Deviation 10.17
|
-0.4 mU*mmol per liter^2
Standard Deviation 3.61
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=45 Participants
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.
|
SRT2104 0.5 g/Day
n=46 Participants
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.
|
SRT2104 1.0 g/Day
n=45 Participants
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.
|
SRT2104 2.0 g/Day
n=45 Participants
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.
|
Placebo
n=46 Participants
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.
|
|---|---|---|---|---|---|
|
Mean HOMA-percentage Cell Beta Function at Day 1 and Day 28
Day 1
|
31.8 Percentage of beta cell function
Standard Deviation 46.38
|
31.2 Percentage of beta cell function
Standard Deviation 35.46
|
27.2 Percentage of beta cell function
Standard Deviation 21.39
|
30.2 Percentage of beta cell function
Standard Deviation 23.03
|
38.3 Percentage of beta cell function
Standard Deviation 38.15
|
|
Mean HOMA-percentage Cell Beta Function at Day 1 and Day 28
Day 28
|
42.9 Percentage of beta cell function
Standard Deviation 57.90
|
32.6 Percentage of beta cell function
Standard Deviation 34.57
|
28.4 Percentage of beta cell function
Standard Deviation 26.48
|
40.9 Percentage of beta cell function
Standard Deviation 48.31
|
42.9 Percentage of beta cell function
Standard Deviation 34.71
|
SECONDARY outcome
Timeframe: Baseline (Day 1) and Day 28Population: ITT Population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
SRT2104 0.25 g/Day
n=34 Participants
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.
|
SRT2104 0.5 g/Day
n=39 Participants
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.
|
SRT2104 1.0 g/Day
n=35 Participants
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.
|
SRT2104 2.0 g/Day
n=35 Participants
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.
|
Placebo
n=41 Participants
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.
|
|---|---|---|---|---|---|
|
Change From Baseline in HOMA-percentage of Beta Cell Function at Day 28
|
8.5 Percentage of beta cell function
Standard Deviation 42.09
|
2.3 Percentage of beta cell function
Standard Deviation 17.87
|
3.1 Percentage of beta cell function
Standard Deviation 26.45
|
7.6 Percentage of beta cell function
Standard Deviation 51.96
|
5.8 Percentage of beta cell function
Standard Deviation 34.02
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
SRT2104 0.25 g/Day
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
SRT2104 0.5 g/Day
Serious events: 1 serious events
Other events: 12 other events
Deaths: 1 deaths
SRT2104 1.0 g/Day
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
SRT2104 2.0 g/Day
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=43 participants at risk
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.
|
SRT2104 0.25 g/Day
n=43 participants at risk
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.
|
SRT2104 0.5 g/Day
n=44 participants at risk
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.
|
SRT2104 1.0 g/Day
n=42 participants at risk
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.
|
SRT2104 2.0 g/Day
n=43 participants at risk
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.
|
|---|---|---|---|---|---|
|
Infections and infestations
Sepsis
|
0.00%
0/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
2.3%
1/44 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/42 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
|
Infections and infestations
Wound infection
|
0.00%
0/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
2.3%
1/44 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/42 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
2.3%
1/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/44 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/42 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
Other adverse events
| Measure |
Placebo
n=43 participants at risk
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.
|
SRT2104 0.25 g/Day
n=43 participants at risk
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.
|
SRT2104 0.5 g/Day
n=44 participants at risk
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.
|
SRT2104 1.0 g/Day
n=42 participants at risk
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.
|
SRT2104 2.0 g/Day
n=43 participants at risk
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.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
4.7%
2/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
2.3%
1/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
9.1%
4/44 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
2.4%
1/42 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
4.7%
2/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
|
Gastrointestinal disorders
Nausea
|
4.7%
2/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
7.0%
3/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
9.1%
4/44 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
2.4%
1/42 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
4.7%
2/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
|
General disorders
Asthenia
|
2.3%
1/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
2.3%
1/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
9.1%
4/44 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/42 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
0.00%
0/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.0%
3/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
2.3%
1/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
6.8%
3/44 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
9.5%
4/42 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
9.3%
4/43 • AE's and SAE's were collected from the start of study medication (Day 1) up to Follow-up (58 days)
Safety Analysis Set Population was used.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER