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Study of the Clinical Activity, Safety, and Tolerability of SRT2104 in Subjects With Moderate to Severe Plaque-Type Psoriasis

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ClinicalTrials.gov Identifier: NCT01154101
Recruitment Status : Completed
First Posted : June 30, 2010
Results First Posted : October 13, 2017
Last Update Posted : October 13, 2017
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline ( Sirtris, a GSK Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Psoriasis
Interventions Drug: Placebo
Drug: SRT2104
Enrollment 40
Recruitment Details A total of 40 participants with moderate to severe plaque-type psoriasis were enrolled. This study was conducted at eight centers in the United States: New York (2); Missouri (1); Oregon (1); Pennsylvania (1); Rhode Island (1); Texas (1); Washington (1), from 07 June 2010 to 09 November 2011.
Pre-assignment Details Participants were asked to sign the informed consent form (ICF) at the Screening Visit, which was conducted within 21 days prior to administration of the first dose of study drug on Day 1.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g No Treatment
Hide Arm/Group Description Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants received SRT2104 0.25 gram (g) capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants in this arm received no treatment. No treatment arm was used when participants were randomized but discontinued prior to dosing.
Period Title: Overall Study
Started 7 9 12 11 1
Completed 7 5 9 9 0
Not Completed 0 4 3 2 1
Reason Not Completed
Adverse Event             0             2             1             1             0
Lost to Follow-up             0             1             0             1             0
Withdrawal by Subject             0             1             2             0             1
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g No Treatment Total
Hide Arm/Group Description Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants received SRT2104 0.25 gram (g) capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants in this arm received no treatment. No treatment arm was used when participants were randomized but discontinued prior to dosing. Total of all reporting groups
Overall Number of Baseline Participants 7 9 12 11 1 40
Hide Baseline Analysis Population Description
Sex and Race assessments were performed for the entire population (40 participants). However, for Age only 39 participants were available (1 participant withdrew from the study from the 'No Treatment group') and hence data was not collected for that participant.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 9 participants 12 participants 11 participants 0 participants 39 participants
51.4  (14.88) 40.6  (16.05) 49.3  (14.41) 44.6  (13.58) 46.4  (14.63)
[1]
Measure Analysis Population Description: For the "no treatment" group: the single participant in this arm had withdrawn from the study, therefore the age data was not collected for this single participant in this arm.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 9 participants 12 participants 11 participants 1 participants 40 participants
Female
1
  14.3%
3
  33.3%
0
   0.0%
5
  45.5%
1
 100.0%
10
  25.0%
Male
6
  85.7%
6
  66.7%
12
 100.0%
6
  54.5%
0
   0.0%
30
  75.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 9 participants 12 participants 11 participants 1 participants 40 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
1
   2.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  14.3%
2
  22.2%
0
   0.0%
1
   9.1%
0
   0.0%
4
  10.0%
White
6
  85.7%
7
  77.8%
10
  83.3%
10
  90.9%
1
 100.0%
34
  85.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
1
   2.5%
1.Primary Outcome
Title Assessment of Clinical Activity by Improvement Score (Using Krueger Criteria): Number of Participants With Good or Excellent Improvement Score Based on Histological Assessments of Skin Biopsies After 12 Weeks of Exposure
Hide Description According to the Krueger criteria, improvement score is classified as Good improvement defined as reduction in epidermal thickness by at least 30% normalized keratinocyte differentiation but most keratinocytes still express K16. Excellent improvement defined as reduction in epidermal thickness to normal or almost normal normalized keratinocyte differentiation and absent keratinocyte expression of K16. No improvement defined as no improvement in epidermal thickness keratinocyte differentiation or K16 expression on keratinocytes. A binomial response was defined for each participant according to whether the participant had an improvement score of "good or excellent improvement" (response=1) or not (response=0). Number of participants with good or excellent improvement score are presented.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Analysis Set (EAS) population comprised of all randomized participants who took at least one dose of study medication, had at least one activity measurement at Baseline, at least one post-Baseline study visit. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 7 6 9 11
Measure Type: Count of Participants
Unit of Measure: Participants
1
  14.3%
3
  50.0%
4
  44.4%
2
  18.2%
2.Primary Outcome
Title Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is 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 or is medically significant. The AE category in the data table includes participants who experienced serious or non-serious adverse events or both.
Time Frame Up to Follow-up (Day 114)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAF) population which comprised of all participants who received at least one dose of study medication.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 7 9 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
AE
3
  42.9%
4
  44.4%
9
  75.0%
11
 100.0%
SAE
0
   0.0%
2
  22.2%
0
   0.0%
1
   9.1%
3.Primary Outcome
Title Number of Participants With Hematology and Coagulation Abnormalities of Potential Clinical Concern
Hide Description Hematology parameters included hemoglobin, hematocrit, red blood cell count, red cell distribution width, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, white blood cell count and complete white blood cell count differential. Coagulation parameters included activated partial thromboplastin time and prothrombin time/international normalized ratio. The potential clinical concern range for hematology parameters were: white blood cell count (low: <0.67x10^9/Liter x lower limit of normal [LLN] and high: >1.82x10^9/L x upper limit of normal [ULN]), neutrophil count: (low: <0.83x10^9/Liter x LLN), hemoglobin (low: <0.85 gram/Liter x LLN and high: >1.03 gram/Liter x ULN for males and >1.13 gram/Liter x ULN for females), hematocrit with units ratio (high: >1.02 x ULN for males and >1.17 x ULN for females), platelet count (low: <0.67x10^9/Liter x LLN and high >1.57x10^9/Liter x ULN) and lymphocytes (low: <0.81x10^9/Liter x LLN).
Time Frame Up to Follow-up (Day 114)
Hide Outcome Measure Data
Hide Analysis Population Description
SAF Population.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 7 9 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
1
   8.3%
2
  18.2%
4.Primary Outcome
Title Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
Hide Description The potential clinical concern range for clinical chemistry parameters were: Albumin:(low: <0.86 gram/Liter x LLN), Calcium:(low: <0.91 millimol/Liter [mmol/L] x LLN and high: >1.06 mmol/L x ULN), Creatinine: (high: >1.3 mmol /L x ULN), Glucose: (low: <0.71 mmol/L x LLN, high: >1.41 mmol/L x ULN), Magnesium: (low: <0.63 mmol/L x LLN, high: >1.03 mmol/L x ULN), Phosphorus: (low: <0.8 mmol/L x LLN, high: >1.14 mmol/L x ULN), Sodium: (low: <0.96 mmol/L x LLN, high: >1.03 mmol/L x ULN), Urea: (high: >1.5 mmol/L x ULN), Gamma glutamyl transferase: (high: >2 International units per L x ULN), Total bilirubin (high: 1.5 x ULN), both alanine amino transferase and aspartate amino transferase (high:≥ 2x ULN Units/L) and Bicarbonate: (low: <18 mmol/L and high: >32 mmol/L). Number of participants with clinical chemistry abnormalities of potential clinical importance are presented.
Time Frame Up to Follow-up (Day 114)
Hide Outcome Measure Data
Hide Analysis Population Description
SAF Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 7 9 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
4
  57.1%
3
  33.3%
5
  41.7%
5
  45.5%
5.Primary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Values
Hide Description 12-lead ECG was performed in the rested state with the participant in the supine position with ECG leads on for at least 5 minutes prior to ECG recording. ECGs included PR (PQ), QRS, QT and QT corrected by Bazett's formula (QTcB), QT corrected by Fridericia's formula (QTcF) intervals. Identification of any conduction abnormalities were recorded in the eCRF. If a participant's QTc intervals were prolonged, then the ECG was done in triplicate with results reported as an average of the three ECGs. Number of participants with abnormal electrocardiogram (ECG) values are presented.
Time Frame Up to Follow-up (Day 114)
Hide Outcome Measure Data
Hide Analysis Population Description
SAF Population.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 7 9 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
3
  42.9%
1
  11.1%
4
  33.3%
6
  54.5%
6.Primary Outcome
Title Number of Participants With Vital Signs of Potential Clinical Importance
Hide Description Vital sign assessments included measurements of resting heart rate and blood pressure. Potential clinical concern range for systolic blood pressure: <85 and >160 millimeter of mercury (mmHg), for diastolic: <45 and >100 mmHg and heart rate: <40 and >110 beats per minute. Number of participants with vital signs of potential clinical importance are presented.
Time Frame Up to Follow-up (Day 114)
Hide Outcome Measure Data
Hide Analysis Population Description
SAF Population.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 7 9 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2
  18.2%
7.Secondary Outcome
Title Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure
Hide Description PASI score was determined by evaluation of body surface area (BSA) covered by plaque psoriasis in 4 areas (head/neck, arms, trunk and legs with area score of 0.1, 0.2, 0.3 and 0.4 respectively). This test included combination of both degree of involvement (assessed as per the % of affected body area using a 7-point scale such that 0=0% involvement, 1=1-9%, 2=10-29%, 3=30-49%, 4=50-69%, 5=70-89% and 6=90-100%) and severity (evaluated individually using a 5-point scale that ranged as 0=No evidence of sign, 1=slight evidence, 2=moderate evidence, 3=marked evidence and 4=very marked, most severe evidence of sign) of erythema, induration and desquamation in each of the same 4 areas. PASI score ranges from 0 (no psoriasis) to 72 (worse psoriasis). Final PASI=(sum of severity score for each area)x(% body affected score x area score).
Time Frame Weeks 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set (EAS) population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 7 9 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
Week 4: 25% Improvement in PASI score from Day 1 Number Analyzed 7 participants 9 participants 12 participants 11 participants
2
  28.6%
1
  11.1%
3
  25.0%
7
  63.6%
Week 4: 50% Improvement in PASI score from Day 1 Number Analyzed 7 participants 9 participants 12 participants 11 participants
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
Week 4: 75% Improvement in PASI score from Day 1 Number Analyzed 7 participants 9 participants 12 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Week 8: 25% Improvement in PASI score from Day 1 Number Analyzed 7 participants 7 participants 11 participants 11 participants
2
  28.6%
2
  28.6%
5
  45.5%
8
  72.7%
Week 8: 50% Improvement in PASI score from Day 1 Number Analyzed 7 participants 7 participants 11 participants 11 participants
1
  14.3%
2
  28.6%
4
  36.4%
4
  36.4%
Week 8: 75% Improvement in PASI score from Day 1 Number Analyzed 7 participants 7 participants 11 participants 11 participants
0
   0.0%
1
  14.3%
2
  18.2%
0
   0.0%
Week 12: 25% Improvement in PASI score from Day 1 Number Analyzed 7 participants 6 participants 9 participants 11 participants
2
  28.6%
2
  33.3%
6
  66.7%
8
  72.7%
Week 12: 50% Improvement in PASI score from Day 1 Number Analyzed 7 participants 6 participants 9 participants 11 participants
2
  28.6%
2
  33.3%
3
  33.3%
4
  36.4%
Week 12: 75% Improvement in PASI score from Day 1 Number Analyzed 7 participants 6 participants 9 participants 11 participants
1
  14.3%
2
  33.3%
2
  22.2%
1
   9.1%
8.Secondary Outcome
Title Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure
Hide Description The severity of psoriatic lesions over the whole body were assessed by the investigator using the PGA scoring system. A 0 to 6 point rating scale was used, as follows: 0 = Clear (no signs of psoriasis), 1 = Almost clear (slight elevation, scale and/or erythema), 2 = Mild (mild plaque elevation, scale and/or erythema), 3 = Mild to moderate (mild plaque elevation with moderate erythema and/or scale), 4 = Moderate (moderate plaque elevation, scale and/or erythema), 5 = Moderate to severe (marked plaque elevation, scale and/or erythema), 6 = Severe (very marked plaque elevation, scale and/or erythema). Higher scores indicated worse psoriasis. Participants in the SRT2104 0.25 g dose group inadvertently used an incorrect version of the PGA scale and thus do not have PGA data available. Participants in the SRT2104 0.25 g dose group inadvertently used an incorrect version of the PGA scale and thus do not have PGA data available.
Time Frame Weeks 4, 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
EAS Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 7 0 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
Week 4: Very Severe Number Analyzed 5 participants 0 participants 12 participants 11 participants
1
  20.0%
0
   0.0%
0
   0.0%
Week 4: Severe Number Analyzed 5 participants 0 participants 12 participants 11 participants
1
  20.0%
2
  16.7%
1
   9.1%
Week 4: Moderate Number Analyzed 5 participants 0 participants 12 participants 11 participants
2
  40.0%
9
  75.0%
4
  36.4%
Week 4: Mild Number Analyzed 5 participants 0 participants 12 participants 11 participants
1
  20.0%
1
   8.3%
6
  54.5%
Week 4: Minimal Number Analyzed 5 participants 0 participants 12 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 4: Clear Number Analyzed 5 participants 0 participants 12 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 8: Very Severe Number Analyzed 5 participants 0 participants 11 participants 11 participants
1
  20.0%
0
   0.0%
0
   0.0%
Week 8: Severe Number Analyzed 5 participants 0 participants 11 participants 11 participants
1
  20.0%
1
   9.1%
0
   0.0%
Week 8: Moderate Number Analyzed 5 participants 0 participants 11 participants 11 participants
2
  40.0%
6
  54.5%
3
  27.3%
Week 8: Mild Number Analyzed 5 participants 0 participants 11 participants 11 participants
1
  20.0%
3
  27.3%
7
  63.6%
Week 8: Minimal Number Analyzed 5 participants 0 participants 11 participants 11 participants
0
   0.0%
1
   9.1%
1
   9.1%
Week 8: Clear Number Analyzed 5 participants 0 participants 11 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 12: Very Severe Number Analyzed 5 participants 0 participants 9 participants 11 participants
1
  20.0%
0
   0.0%
0
   0.0%
Week 12: Severe Number Analyzed 5 participants 0 participants 9 participants 11 participants
1
  20.0%
2
  22.2%
0
   0.0%
Week 12: Moderate Number Analyzed 5 participants 0 participants 9 participants 11 participants
2
  40.0%
2
  22.2%
5
  45.5%
Week 12: Mild Number Analyzed 5 participants 0 participants 9 participants 11 participants
1
  20.0%
3
  33.3%
3
  27.3%
Week 12: Minimal Number Analyzed 5 participants 0 participants 9 participants 11 participants
0
   0.0%
2
  22.2%
3
  27.3%
Week 12: Clear Number Analyzed 5 participants 0 participants 9 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
9.Secondary Outcome
Title Area Under Curve (AUC) of 12 Weeks of Dosing With 0.25 g, 0.5 g and 1.0 g SRT2104 in the Fed State in Participants
Hide Description A total of five blood samples (6 milliliter [mL] each) were obtained from each participant up to Week 12, for determination of SRT2104 plasma concentrations. No two samples were separated by less than an hour. One pre-dose sample was collected prior to taking study medication (30 minutes or less before dosing) at any Visit 4 (Week 4), Visit 6 (Week 8) or Visit 8 (Week 12). A single pharmacokinetic (PK) sample was collected in the time interval of 0.5 to 2 hours post-dose and also 3 to 6 hours post-dose at any Visit 4 (Week 4), Visit 6 (Week 8) or Visit 8 (Week 12). Two PK samples were collected in the time interval of 6 to 22 hours post dose at any Visit 4 (Week 4), Visit 6 (Week 8) or Visit 8 (Week 12).
Time Frame Pre-dose (30 minutes or less before dosing: 1 sample), 0.5 to 2 hours and 3 to 6 hours post-dose (1 sample), 6 to 22 hours post-dose (2 samples) up to Week 12
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Hide Analysis Population Description
PK population which comprised of all participants who received at least one dose of SRT2104 for whom a PK sample was obtained and analyzed.
Arm/Group Title SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 9 11 11
Mean (Standard Deviation)
Unit of Measure: Nanogram x hour/milliliter (ng*h/mL)
2148.08  (1247.182) 4189.46  (2143.021) 8358.45  (7466.966)
10.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of 12 Weeks of Dosing With 250 Milligrams (mg), 500 mg and 1000 mg SRT2104 in the Fed State in Participants
Hide Description A total of five blood samples (6 mL each) were obtained from each participant at any Visit 4 (Day 28 or Week 4), Visit 6 (Day 56 or Week 8) or Visit 8 (Day 84 or Week 12), for determination of SRT2104 plasma concentrations. No two samples were separated by less than an hour. One pre-dose sample was collected prior to taking study medication (30 minutes or less before dosing) at any Visit 4 (Day 28 or Week 4), Visit 6 (Day 56 or Week 8) or Visit 8 (Day 84 or Week 12). A single pharmacokinetic (PK) sample was collected in the time interval of 0.5 to 2 hours post-dose and also 3 to 6 hours post-dose at any Visit 4 (Day 28 or Week 4), Visit 6 (Day 56 or Week 8) or Visit 8 (Day 84 or Week 12). Two PK samples were collected in the time interval of 6 to 22 hours post dose at any Visit 4 (Day 28 or Week 4), Visit 6 (Day 56 or Week 8) or Visit 8 (Day 84 or Week 12).
Time Frame One sample: Pre-dose (30 minutes or less before dosing), One sample: 0.5 to 2 hours post-dose and 3 to 6 hours post-dose and 2 samples 6 to 22 hours post dose, at any Visit 4 (Day 28 or Week 4), Visit 6 (Day 56 or Week 8) or Visit 8 (Day 84 or Week 12)
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Hide Analysis Population Description
PK population.
Arm/Group Title SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Overall Number of Participants Analyzed 9 11 11
Mean (Standard Deviation)
Unit of Measure: ng/mL
261.64  (134.403) 406.67  (237.787) 1005.89  (813.346)
11.Secondary Outcome
Title Change From Baseline in Fibroblast Growth Factor 21 (FGF21) as an Indicator of the Pharmacodynamic Effects of SRT2104
Hide Description The pharmacodynamic effects of SRT2104 was measured by biomarkers of psoriatic disease activity and/or sirtuin pathway activation (hsCRP and FGF21) in blood samples. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Day 1) and Days 28, 56 and 84
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Hide Analysis Population Description
EAS population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 84 days.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 84 days.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 84 days.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 84 days.
Overall Number of Participants Analyzed 7 9 12 11
Mean (Standard Deviation)
Unit of Measure: Picogram per milliliter
Day 28 Number Analyzed 6 participants 6 participants 11 participants 9 participants
-61.67  (269.031) -94.53  (154.104) 56.93  (177.244) 329.82  (930.329)
Day 56 Number Analyzed 5 participants 5 participants 9 participants 9 participants
-67.04  (276.937) -72.72  (366.774) 148.93  (305.634) 268.39  (961.010)
Day 84 Number Analyzed 5 participants 4 participants 9 participants 9 participants
-86.12  (300.144) -189.60  (364.475) 58.31  (223.237) -673.32  (1590.594)
12.Secondary Outcome
Title Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) as an Indicator of the Pharmacodynamic Effects of SRT2104
Hide Description The pharmacodynamic effects of SRT2104 was measured by biomarkers of psoriatic disease activity and/or sirtuin pathway activation (hsCRP and FGF21) in blood samples. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.
Time Frame Baseline (Day 1) and Days 28, 56 and 84
Hide Outcome Measure Data
Hide Analysis Population Description
EAS population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description:
Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 84 days.
Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 84 days.
Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 84 days.
Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 84 days.
Overall Number of Participants Analyzed 7 9 12 11
Mean (Standard Deviation)
Unit of Measure: mg per Liter
Day 28 Number Analyzed 7 participants 8 participants 10 participants 10 participants
0.11  (2.330) -0.14  (1.148) 1.18  (1.954) -0.96  (2.211)
Day 56 Number Analyzed 7 participants 6 participants 7 participants 10 participants
0.59  (3.552) -0.18  (1.897) -1.31  (3.261) -0.48  (2.640)
Day 84 Number Analyzed 7 participants 5 participants 8 participants 10 participants
0.66  (3.895) -0.16  (1.055) -0.75  (3.159) 0.27  (1.351)
Time Frame Up to Follow-up (Day 114)
Adverse Event Reporting Description SAF Population was used.
 
Arm/Group Title Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Hide Arm/Group Description Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks. Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
All-Cause Mortality
Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)   0/9 (0.00%)   0/12 (0.00%)   0/11 (0.00%) 
Hide Serious Adverse Events
Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)   2/9 (22.22%)   0/12 (0.00%)   1/11 (9.09%) 
Gastrointestinal disorders         
Pancreatitis  1  0/7 (0.00%)  1/9 (11.11%)  0/12 (0.00%)  0/11 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Blood bilirubin increased  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Respiratory, thoracic and mediastinal disorders         
Pneumonitis  1  0/7 (0.00%)  1/9 (11.11%)  0/12 (0.00%)  0/11 (0.00%) 
1
Term from vocabulary, MedDRA 12.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo SRT2104 0.25 g SRT2104 0.5 g SRT2104 1.0 g
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/7 (42.86%)   3/9 (33.33%)   9/12 (75.00%)   11/11 (100.00%) 
Eye disorders         
Eye pain  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Gastrointestinal disorders         
Nausea  1  0/7 (0.00%)  1/9 (11.11%)  0/12 (0.00%)  1/11 (9.09%) 
Vomiting  1  0/7 (0.00%)  1/9 (11.11%)  0/12 (0.00%)  1/11 (9.09%) 
Abdominal pain upper  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  0/11 (0.00%) 
Constipation  1  1/7 (14.29%)  0/9 (0.00%)  0/12 (0.00%)  0/11 (0.00%) 
Diarrhoea  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Dyspepsia  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  0/11 (0.00%) 
Flatulence  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Food poisoning  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Toothache  1  0/7 (0.00%)  1/9 (11.11%)  0/12 (0.00%)  0/11 (0.00%) 
General disorders         
Fatigue  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  2/11 (18.18%) 
Pyrexia  1  1/7 (14.29%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Malaise  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Oedema peripheral  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  0/11 (0.00%) 
Infections and infestations         
Upper respiratory tract infection * 1  1/7 (14.29%)  0/9 (0.00%)  1/12 (8.33%)  1/11 (9.09%) 
Furuncle  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Influenza  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  0/11 (0.00%) 
Nasal abscess  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Pharyngitis  1  1/7 (14.29%)  0/9 (0.00%)  0/12 (0.00%)  0/11 (0.00%) 
Sinusitis  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  0/11 (0.00%) 
Skin infection  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  0/11 (0.00%) 
Urinary tract infection  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Viral infection  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Injury, poisoning and procedural complications         
Contusion  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Injury  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Joint sprain  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  0/11 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  2/11 (18.18%) 
Aspartate aminotransferase increased  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  2/11 (18.18%) 
Hepatic enzyme increased  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  1/11 (9.09%) 
Blood phosphorus decreased  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Blood potassium increased  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Metabolism and nutrition disorders         
Dehydration  1  0/7 (0.00%)  1/9 (11.11%)  0/12 (0.00%)  0/11 (0.00%) 
Diabetes mellitus  1  0/7 (0.00%)  1/9 (11.11%)  0/12 (0.00%)  0/11 (0.00%) 
Hypokalaemia  1  0/7 (0.00%)  1/9 (11.11%)  0/12 (0.00%)  0/11 (0.00%) 
Hyponatraemia  1  0/7 (0.00%)  1/9 (11.11%)  0/12 (0.00%)  0/11 (0.00%) 
Musculoskeletal and connective tissue disorders         
Psoriatic arthropathy  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  2/11 (18.18%) 
Pain in extremity  1  0/7 (0.00%)  0/9 (0.00%)  1/12 (8.33%)  1/11 (9.09%) 
Arthralgia  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Back pain  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Flank pain  1  1/7 (14.29%)  0/9 (0.00%)  0/12 (0.00%)  0/11 (0.00%) 
Myalgia  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Osteoarthritis  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Nervous system disorders         
Dizziness  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  3/11 (27.27%) 
Headache  1  0/7 (0.00%)  0/9 (0.00%)  2/12 (16.67%)  1/11 (9.09%) 
Disturbance in attention  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Paraesthesia  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Psychiatric disorders         
Depression  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Skin and subcutaneous tissue disorders         
Pruritus  1  1/7 (14.29%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Actinic keratosis  1  0/7 (0.00%)  0/9 (0.00%)  0/12 (0.00%)  1/11 (9.09%) 
Erythema annulare  1  1/7 (14.29%)  0/9 (0.00%)  0/12 (0.00%)  0/11 (0.00%) 
Ingrowing nail  1  1/7 (14.29%)  0/9 (0.00%)  0/12 (0.00%)  0/11 (0.00%) 
1
Term from vocabulary, MedDRA 12.0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline ( Sirtris, a GSK Company )
ClinicalTrials.gov Identifier: NCT01154101    
Other Study ID Numbers: 114296
First Submitted: April 22, 2010
First Posted: June 30, 2010
Results First Submitted: August 7, 2017
Results First Posted: October 13, 2017
Last Update Posted: October 13, 2017