An Adaptive Phase II Study to Evaluate the Efficacy, Pharmacodynamics, Safety and Tolerability of GSK2586184

Percentage Inhibition from Baseline of interferon (IFN) Transcriptional Biomarkers at Week 2

Mean reduction (40%) from Baseline of the IFN transcriptional signature biomarker was monitored at Week 2. Percentage (Per) inhibition (=\[(Day x-Baseline)/Baseline\]\*-100), was the Per reduction from Baseline (Day1) and evaluated in any pre-designated panels of genes i.e. Addenbrookes 1, Addenbrookes 2, JAK439, PD, Panel Stripping, Flare and Transcription. Analysis was performed using a repeated measures model with covariates of treatment, baseline, Day, Day by baseline and Day by treatment interactions. Only those Par available at the specified time points were analysed (n=X,X,X,X,X). Different Par may have been analysed at different time points, so the overall number of Par analysed reflects everyone in the Intent To Treat (ITT) Population i.e. Par randomised to treatment, received \>=1 dose of study medication and had \>=1 valid post dose assessment

Time frame: Baseline(Day1) and Week 2

Change from Baseline of SELENA SLEDAI score at indicated time points up to Week 16

The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is a validated index for assessing SLE disease activity. It is a weighted index in which signs and symptoms, laboratory tests, and physician's assessment for each of 9 organ systems are given a weighted score and summed, if present at the time of the visit or in the preceding 10 days. Modified version of SLEDAI is Safety of Estrogen in Lupus National Assessment (SELENA) SLEDAI where the maximum theoretical score for the SELENA SLEDAI was 105 with 0 indicating inactive disease. Baseline value is defined as Day 1 (pre-dose) SELENA SLEDAI score.

Time frame: Baseline(Day1), Weeks 2, 4, 6, 8, 10, 12 and 16

Change from Baseline in systolic blood pressure and diastolic blood pressure at the indicated time points up to Week 16

Change from Baseline in systolic blood pressure (BP) and diastolic BP is summarized for each post-Baseline assessment up to Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day1), Weeks 2, 4, 6, 8, 10, 12 and 16

Change from Baseline in heart rate at the indicated time points up to Week 16

Change from Baseline in sitting and supine heart rate is summarized for each post-Baseline assessment up to Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last pre-treatment value observed.

Time frame: Baseline (Day 1), Weeks 2, 4, 6, 8, 10, 12 and 16

Change from Baseline in temperature at the indicated time points up to Week 16

Change from Baseline in temperature is summarized for each post-Baseline assessment up to Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline (Day 1), Weeks 2, 4, 6, 8, 10, 12 and 16

Change from Baseline in albumin, globulin and protein at the indicated time points up to Week 16

Change from Baseline in the albumin, globulin and protein values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline (Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from baseline in alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase, gamma glutamyl transferase and lactate dehydrogenase at the indicated time points up to Week 16

Change from Baseline in the alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), creatine kinase (CK), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in anion gap, calcium, cholesterol, chloride, carbon dioxide, glucose, HDL cholesterol, potassium, LDL cholesterol, magnesium, phosphate, soidium, triglycerides, urea, VLDL cholesterol at the indicated time points up to Week 16

Change from Baseline in the anion gap, calcium, ionised calcium, cholesterol, chloride, carbon dioxide, glucose, high density lipoprotein (HDL) cholesterol (fasted and not fasted), potassium, low density lipoprotein (LDL) cholesterol (fasted and not fasted), magnesium, phosphate, sodium, triglycerides (fasted and not fasted), urea and very low density lipoprotein (VLDL) cholesterol values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline (Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in bilirubin, creatinine, iron binding capacity, iron and urate at the indicated time points up to Week 16

Change from Baseline in the bilirubin, direct and indirect bilirubin, creatinine, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), iron and uric acid values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in albumin/globulin, BUN/creatinine and transferrin saturation at the indicated time points up to Week 16

Change from baseline in the albumin/globulin, blood urea nitrogen (BUN)/creatinine and transferrin saturation values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in creatinine clearance at the indicated time points up to Week 16

Change from Baseline in the Creatinine Clearance values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline (Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, neutrophils segmented (SG), platelets and leukocytes at the indicated time points up to Week 16

Change from Baseline in the basophils, eosinophils, lymphocytes, monocytes, neutrophils, neutrophils segmented (SG), platelets and leukocytes values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes, neutrophils SG/leukocytes and erythrocyte distribution width (EDW) at the indicated time points up to Week 16

Change from Baseline in the basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes, neutrophils segmented (SG)/leukocytes and erythrocyte distribution width (EDW) values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in erythrocytes and reticulocytes at the indicated time points up to Week 16

Change from Baseline in the erythrocyte and reticulocyte values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline (Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in hemoglobin and erythrocyte mean corpuscular hemoglobin concentration (EMCHC) at the indicated time points up to Week 16

Change from Baseline in the hemoglobin and erythrocyte mean corpuscular hemoglobin concentration (EMCHC) values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in erythrocyte mean corpuscular hemoglobin (EMCH) at the indicated time points up to Week 16

Change from Baseline in the hemoglobin and erythrocyte mean corpuscular hemoglobin (EMCH) values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in erythrocyte mean corpuscular volume (EMCV) and mean platelet volume (MPV) at the indicated time points up to Week 16

Change from Baseline in the erythrocyte mean corpuscular volume (EMCV) and mean platelet volume (MPV) values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in hematocrit and reticulocytes/erythrocytes at the indicated time points up to Week 16

Change from Baseline in the hematocrit and reticulocytes/erythrocytes values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16

Number of participants with urinalysis data at the indicated time points up to Week 16

Number of participants with negative and positives (trace, +, ++ and +++) data for urine glucose (UGLU), urine ketones (UKET) and urine occult blood (UOB) are summarized for each post-Baseline assessment until Week 16. Urinalysis was performed by dipstick method. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in urine protein at the indicated time points up to Week 16

Change from Baseline in the urine protein values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16

Change from Baseline in urine protein/creatinine at the indicated time points up to Week 16

Change from Baseline in the urine protein/creatinine values are summarized for each post-Baseline assessment until Week 16. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Time frame: Baseline(Day 1), Weeks 2, 3, 4, 5, 6, 8, 10, 12 and 16

Number of participants with any adverse events (AEs) and any serious adverse events (SAEs) up to Week 16

An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An 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. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect, important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

Time frame: Up to Week 16

Number of participants with severity Grade 1, 2, 3, 4 and 5 adverse events (AEs)

The Common Terminology Criteria for Adverse Events (CTCAE, Version 4) has categorised AEs in five grades. Grade refers to the severity of the AE. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

Time frame: Up to 16 Weeks