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.

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.

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.

Safety Analysis Set (SAF) population which comprised of all participants who received at least one dose of study medication.

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).

SAF Population.

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.

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

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.

SAF Population.

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.

SAF Population.

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).

Efficacy Analysis Set (EAS) population. Only those participants available at the specified time points were analyzed.

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.

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

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).

PK population which comprised of all participants who received at least one dose of SRT2104 for whom a PK sample was obtained and analyzed.

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).

PK population.

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.

EAS population. Only those participants available at the specified time points were analyzed.

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.

EAS population. Only those participants available at the specified time points were analyzed.