Trial Outcomes & Findings for Study of the Clinical Activity, Safety, and Tolerability of SRT2104 in Subjects With Moderate to Severe Plaque-Type Psoriasis (NCT NCT01154101)

NCT ID: NCT01154101

Last Updated: 2017-10-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2017-10-13

Participant Flow

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.

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.

Participant milestones

Measure	Placebo Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g Eligible participants received SRT2104 0.25 gram (g) capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	No Treatment Eligible participants in this arm received no treatment. No treatment arm was used when participants were randomized but discontinued prior to dosing.
Overall Study STARTED	7	9	12	11	1
Overall Study COMPLETED	7	5	9	9	0
Overall Study NOT COMPLETED	0	4	3	2	1

Reasons for withdrawal

Measure	Placebo Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g Eligible participants received SRT2104 0.25 gram (g) capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	No Treatment Eligible participants in this arm received no treatment. No treatment arm was used when participants were randomized but discontinued prior to dosing.
Overall Study Adverse Event	0	2	1	1	0
Overall Study Lost to Follow-up	0	1	0	1	0
Overall Study Withdrawal by Subject	0	1	2	0	1

Baseline Characteristics

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.

Baseline characteristics by cohort

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 Participants Eligible participants received SRT2104 0.25 gram (g) capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	No Treatment n=1 Participants Eligible participants in this arm received no treatment. No treatment arm was used when participants were randomized but discontinued prior to dosing.	Total n=40 Participants Total of all reporting groups
Age, Continuous	51.4 Years STANDARD_DEVIATION 14.88 • n=7 Participants • 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.	40.6 Years STANDARD_DEVIATION 16.05 • n=9 Participants • 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.	49.3 Years STANDARD_DEVIATION 14.41 • n=12 Participants • 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.	44.6 Years STANDARD_DEVIATION 13.58 • n=11 Participants • 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.	—	46.4 Years STANDARD_DEVIATION 14.63 • n=39 Participants • 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 Female	1 Participants n=7 Participants	3 Participants n=9 Participants	0 Participants n=12 Participants	5 Participants n=11 Participants	1 Participants n=1 Participants	10 Participants n=40 Participants
Sex: Female, Male Male	6 Participants n=7 Participants	6 Participants n=9 Participants	12 Participants n=12 Participants	6 Participants n=11 Participants	0 Participants n=1 Participants	30 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	0 Participants n=9 Participants	0 Participants n=12 Participants	0 Participants n=11 Participants	0 Participants n=1 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Asian	0 Participants n=7 Participants	0 Participants n=9 Participants	1 Participants n=12 Participants	0 Participants n=11 Participants	0 Participants n=1 Participants	1 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants	0 Participants n=9 Participants	0 Participants n=12 Participants	0 Participants n=11 Participants	0 Participants n=1 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	1 Participants n=7 Participants	2 Participants n=9 Participants	0 Participants n=12 Participants	1 Participants n=11 Participants	0 Participants n=1 Participants	4 Participants n=40 Participants
Race (NIH/OMB) White	6 Participants n=7 Participants	7 Participants n=9 Participants	10 Participants n=12 Participants	10 Participants n=11 Participants	1 Participants n=1 Participants	34 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	0 Participants n=9 Participants	0 Participants n=12 Participants	0 Participants n=11 Participants	0 Participants n=1 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=9 Participants	1 Participants n=12 Participants	0 Participants n=11 Participants	0 Participants n=1 Participants	1 Participants n=40 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: 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.

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.

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=6 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=9 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
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	1 Participants	3 Participants	4 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (Day 114)

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

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.

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE) AE	3 Participants	4 Participants	9 Participants	11 Participants
Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE) SAE	0 Participants	2 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (Day 114)

Population: SAF Population.

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).

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Number of Participants With Hematology and Coagulation Abnormalities of Potential Clinical Concern	0 Participants	0 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (Day 114)

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

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.

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance	4 Participants	3 Participants	5 Participants	5 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (Day 114)

Population: SAF Population.

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.

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Number of Participants With Abnormal Electrocardiogram (ECG) Values	3 Participants	1 Participants	4 Participants	6 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (Day 114)

Population: 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.

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Number of Participants With Vital Signs of Potential Clinical Importance	0 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

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

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).

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure Week 4: 25% Improvement in PASI score from Day 1	2 Participants	1 Participants	3 Participants	7 Participants
Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure Week 4: 50% Improvement in PASI score from Day 1	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure Week 4: 75% Improvement in PASI score from Day 1	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure Week 8: 25% Improvement in PASI score from Day 1	2 Participants	2 Participants	5 Participants	8 Participants
Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure Week 8: 50% Improvement in PASI score from Day 1	1 Participants	2 Participants	4 Participants	4 Participants
Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure Week 8: 75% Improvement in PASI score from Day 1	0 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure Week 12: 25% Improvement in PASI score from Day 1	2 Participants	2 Participants	6 Participants	8 Participants
Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure Week 12: 50% Improvement in PASI score from Day 1	2 Participants	2 Participants	3 Participants	4 Participants
Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure Week 12: 75% Improvement in PASI score from Day 1	1 Participants	2 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

Population: 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.

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 4: Very Severe	1 Participants	—	0 Participants	0 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 4: Severe	1 Participants	—	2 Participants	1 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 4: Moderate	2 Participants	—	9 Participants	4 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 4: Mild	1 Participants	—	1 Participants	6 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 4: Minimal	0 Participants	—	0 Participants	0 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 4: Clear	0 Participants	—	0 Participants	0 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 8: Very Severe	1 Participants	—	0 Participants	0 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 8: Severe	1 Participants	—	1 Participants	0 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 8: Moderate	2 Participants	—	6 Participants	3 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 8: Mild	1 Participants	—	3 Participants	7 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 8: Minimal	0 Participants	—	1 Participants	1 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 8: Clear	0 Participants	—	0 Participants	0 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 12: Very Severe	1 Participants	—	0 Participants	0 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 12: Severe	1 Participants	—	2 Participants	0 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 12: Moderate	2 Participants	—	2 Participants	5 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 12: Mild	1 Participants	—	3 Participants	3 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 12: Minimal	0 Participants	—	2 Participants	3 Participants
Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure Week 12: Clear	0 Participants	—	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Population: 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 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).

Outcome measures

Measure	Placebo n=9 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=11 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=11 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
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	2148.08 Nanogram x hour/milliliter (ng*h/mL) Standard Deviation 1247.182	4189.46 Nanogram x hour/milliliter (ng*h/mL) Standard Deviation 2143.021	8358.45 Nanogram x hour/milliliter (ng*h/mL) Standard Deviation 7466.966	—

SECONDARY outcome

Timeframe: 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)

Population: PK population.

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).

Outcome measures

Measure	Placebo n=9 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=11 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=11 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
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	261.64 ng/mL Standard Deviation 134.403	406.67 ng/mL Standard Deviation 237.787	1005.89 ng/mL Standard Deviation 813.346	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Days 28, 56 and 84

Population: 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.

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Change From Baseline in Fibroblast Growth Factor 21 (FGF21) as an Indicator of the Pharmacodynamic Effects of SRT2104 Day 28	-61.67 Picogram per milliliter Standard Deviation 269.031	-94.53 Picogram per milliliter Standard Deviation 154.104	56.93 Picogram per milliliter Standard Deviation 177.244	329.82 Picogram per milliliter Standard Deviation 930.329
Change From Baseline in Fibroblast Growth Factor 21 (FGF21) as an Indicator of the Pharmacodynamic Effects of SRT2104 Day 56	-67.04 Picogram per milliliter Standard Deviation 276.937	-72.72 Picogram per milliliter Standard Deviation 366.774	148.93 Picogram per milliliter Standard Deviation 305.634	268.39 Picogram per milliliter Standard Deviation 961.010
Change From Baseline in Fibroblast Growth Factor 21 (FGF21) as an Indicator of the Pharmacodynamic Effects of SRT2104 Day 84	-86.12 Picogram per milliliter Standard Deviation 300.144	-189.60 Picogram per milliliter Standard Deviation 364.475	58.31 Picogram per milliliter Standard Deviation 223.237	-673.32 Picogram per milliliter Standard Deviation 1590.594

SECONDARY outcome

Timeframe: Baseline (Day 1) and Days 28, 56 and 84

Population: 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.

Outcome measures

Measure	Placebo n=7 Participants Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 Participants Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 Participants Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 Participants Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) as an Indicator of the Pharmacodynamic Effects of SRT2104 Day 28	0.11 mg per Liter Standard Deviation 2.330	-0.14 mg per Liter Standard Deviation 1.148	1.18 mg per Liter Standard Deviation 1.954	-0.96 mg per Liter Standard Deviation 2.211
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) as an Indicator of the Pharmacodynamic Effects of SRT2104 Day 56	0.59 mg per Liter Standard Deviation 3.552	-0.18 mg per Liter Standard Deviation 1.897	-1.31 mg per Liter Standard Deviation 3.261	-0.48 mg per Liter Standard Deviation 2.640
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) as an Indicator of the Pharmacodynamic Effects of SRT2104 Day 84	0.66 mg per Liter Standard Deviation 3.895	-0.16 mg per Liter Standard Deviation 1.055	-0.75 mg per Liter Standard Deviation 3.159	0.27 mg per Liter Standard Deviation 1.351

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

SRT2104 0.25 g

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

SRT2104 0.5 g

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

SRT2104 1.0 g

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=7 participants at risk Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 participants at risk Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 participants at risk Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 participants at risk Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Gastrointestinal disorders Pancreatitis	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	11.1% 1/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Investigations Alanine aminotransferase increased	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Investigations Blood bilirubin increased	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	11.1% 1/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.

Other adverse events

Measure	Placebo n=7 participants at risk Eligible participants received SRT2104 matching placebo capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.25 g n=9 participants at risk Eligible participants received SRT2104 0.25 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 0.5 g n=12 participants at risk Eligible participants received SRT2104 0.5 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.	SRT2104 1.0 g n=11 participants at risk Eligible participants received SRT2104 1.0 g capsules, orally, once daily after meal (at the same time every dosing day) for 12 weeks.
Infections and infestations Upper respiratory tract infection	14.3% 1/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Infections and infestations Furuncle	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Infections and infestations Influenza	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Infections and infestations Nasal abscess	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Infections and infestations Pharyngitis	14.3% 1/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Infections and infestations Sinusitis	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Infections and infestations Skin infection	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Infections and infestations Urinary tract infection	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Infections and infestations Viral infection	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Gastrointestinal disorders Nausea	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	11.1% 1/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Gastrointestinal disorders Vomiting	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	11.1% 1/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Gastrointestinal disorders Constipation	14.3% 1/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Gastrointestinal disorders Diarrhoea	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Gastrointestinal disorders Dyspepsia	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Gastrointestinal disorders Flatulence	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Gastrointestinal disorders Food poisoning	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Gastrointestinal disorders Toothache	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	11.1% 1/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	18.2% 2/11 • Up to Follow-up (Day 114) SAF Population was used.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Musculoskeletal and connective tissue disorders Flank pain	14.3% 1/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Nervous system disorders Dizziness	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	27.3% 3/11 • Up to Follow-up (Day 114) SAF Population was used.
Nervous system disorders Headache	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	16.7% 2/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Nervous system disorders Disturbance in attention	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Nervous system disorders Paraesthesia	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Investigations Alanine aminotransferase increased	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	18.2% 2/11 • Up to Follow-up (Day 114) SAF Population was used.
Investigations Aspartate aminotransferase increased	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	18.2% 2/11 • Up to Follow-up (Day 114) SAF Population was used.
Investigations Hepatic enzyme increased	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Investigations Blood phosphorus decreased	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Investigations Blood potassium increased	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Skin and subcutaneous tissue disorders Pruritus	14.3% 1/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Skin and subcutaneous tissue disorders Erythema annulare	14.3% 1/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Skin and subcutaneous tissue disorders Ingrowing nail	14.3% 1/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
General disorders Fatigue	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	18.2% 2/11 • Up to Follow-up (Day 114) SAF Population was used.
General disorders Pyrexia	14.3% 1/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
General disorders Malaise	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
General disorders Oedema peripheral	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Injury, poisoning and procedural complications Contusion	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Injury, poisoning and procedural complications Injury	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Injury, poisoning and procedural complications Joint sprain	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	8.3% 1/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Metabolism and nutrition disorders Dehydration	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	11.1% 1/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	11.1% 1/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	11.1% 1/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	11.1% 1/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/11 • Up to Follow-up (Day 114) SAF Population was used.
Eye disorders Eye pain	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF Population was used.
Psychiatric disorders Depression	0.00% 0/7 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/9 • Up to Follow-up (Day 114) SAF Population was used.	0.00% 0/12 • Up to Follow-up (Day 114) SAF Population was used.	9.1% 1/11 • Up to Follow-up (Day 114) SAF 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