An AE is defined as 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. 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

An AE is defined as 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. 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

Blood samples for hematology assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up. Hematology parameter: Total Neutrophil count was assessed for abnormal value of PCI. The range of PCI value was: \<0.83 x lower limit normal (LLN) with unit x10\^9 per liter

Blood samples for hematology assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Hematology parameters: Hematocrit (unit: ratio) and hemoglobin (unit: grams per liter \[g/L\]), were assessed for abnormal values of PCI. The PCI range for hematocrit was: \>0.075 decrease from Baseline (low), \>1.02 x upper limit normal (ULN) (high-male), \>1.17 x ULN (high-female). The PCI range for hemoglobin was: \>25 decrease from Baseline (low), \>1.03 x ULN (high-male), \>1.13 x ULN (high-female). Data has been presented for the number of participants with hematology data values high from the PCI range in a consolidated format.

Blood samples for chemistry assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up. Clinical chemistry parameter: Glucose (unit: millimoles per liter \[mmol/L\]) was assessed for abnormal high value of PCI. The normal range was 3.6 to 5.5 mmol/L

Blood samples for chemistry assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Clinical chemistry parameters: Aspartate amino transferase (unit: international unit per liter \[IU/L\]) and Total bilirubin (unit: micromoles per liter (µmol/L) were assessed for abnormal values of PCI. For aspartate aminotransferase the PCI range was \>=2 x ULN (high). For total bilirubin the PCI range was \>=1.5 x ULN (high).

Urinalysis parameters: Urine occult blood, Urine Glucose, Urine ketones and Urine protein were assessed for abnormal findings by dipstick analysis. The abnormalities were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome.

Urinalysis parameters: Urine occult blood, Urine glucose, Urine ketones, Urine protein, White blood cells were assessed for abnormal findings by dipstick analysis. The abnormal findings were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome.

Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urine albumin was assessed using quantitative analysis.

Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urine albumin was assessed using quantitative analysis.

Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral.

Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral.

Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine .

Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine .

Assessment of vital signs (including systolic, diastolic blood pressure and heart rate) was performed at one time point at Screening, at follow-up and pre-breakfast on Day -1. On Day 1, they were taken at pre-breakfast, 1 hour, 3, 4, 6, 10, 16 and 24 hours post-dose. Assessments were made in triplicate at the pre-breakfast time point, and single assessments were made at all other times. Assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. PCI value of systolic blood pressure: \<85 and \>160 millimeter of mercury (mmHg). PCI value of diastolic blood pressure: \<45 and \>100 mmHg. PCI value of heart rate: \<40 and \>110 beats per minute.

Assessment of vital signs (including systolic and diastolic blood pressure and heart rate) was performed at Screening, pre-breakfast on Days -1 to 14 in a fasting state early in the morning (prior to morning dosing on Days 1-14), and at Follow-up. On Days 1, 7 and 14, they were taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes.

ECGs were taken at Screening, pre-breakfast on Day -1, on Day 1 (pre-breakfast, 1 hour, 2, 3, 4, 6, 8, 13, 24hours post-dose), and at follow-up. Assessments were made in triplicate on Day 1 at the pre-breakfast time point, and single assessments were made at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS).

ECGs were taken at Screening, pre-breakfast on Day -1 and at Follow-up. On Days 1, 7 and 14 ECGs were taken pre-breakfast (fasting) and at 1, 2, 4, 6, 8, 12 and 24hours post-dose. Triplicate ECGs were taken at the pre-breakfast time point, and single assessments were taken at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS).

Blood samples for the determination of pharmacokinetics (PK) were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-last) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data.

Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only.

Outcome measure was added with caveat "as data permits". The data for CL/F was not collected.

Outcome measure was added with caveat "as data permits". The data for V/F was not collected.

Outcome measure was added with caveat "as data permits". The data for AUC (0-inf) was not collected.

Outcome measure was added with caveat "as data permits". The data for t1/2 was not collected.

Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data.

Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only.

Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-10) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

Outcome measure was added with caveat "as data permits". The data for T1/2 was not collected.

Accumulation ratio (Ro) was derived as: Ro = Day 14 morning AUC(0-10)/Day 1 morning AUC(0-10) (for BID regimens only). Ro = Day 14 AUC(0-24)/Day 1 AUC(0-24) (for both BID and once daily regimens). Accumulation ratio (RCmax)= Day 14 Cmax/Day 1 Cmax. RCmax was not computed for each dosing period (morning and evening).

Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.

Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.

Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.

Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.

Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner.

Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner.

Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. Weighted mean were assessed for (0-12) and (0-24). AUC with respect to that time interval was calculated using the linear trapezoidal rule. The weighted mean was determined by dividing the AUC by the observed length of the collection interval (time of last assessment - time of first assessment in hours). In order for the AUC to be calculated, the first and last time points and at least one additional assessment falling between the two must be non-missing.

Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. AUC with respect to that time interval was calculated using the linear trapezoidal rule. The weighted mean was determined by dividing the AUC by the observed length of the collection interval (time of last assessment - time of first assessment in hours). In order for the AUC to be calculated, the first and last time points and at least one additional assessment falling between the two must be non-missing.

Data was not collected for this outcome measure.

An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell count (WBC; absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit, reticulocytes and basophils. It was assessed on Screening, Day -1, Day 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters (hemoglobin, high) for which at least one value of PCI was reported are summarized. Null data is not presented.

Clinical chemistry parameters included blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), total and direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, glucose fasting, gamma glutamyltransferase (GGT), albumin, sodium, magnesium, phosphorus inorganic, calcium, total carbon dioxide (CO2), alkaline phosphatase (ALP), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, free fatty acid (non-esterified fatty acids; \[NEFA\]), high-density lipoprotein (HDL) cholesterol and total protein. It was assessed on Screening, Day -1, Day 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented.

Twelve-lead ECGs was obtained in a supine position at each time point during the study using an ECG machine that automatically measured PR, QRS, QT and QTc intervals (QT duration corrected for heart rate by Bazett's formula \[QTcB\] and Fridericia's formula \[QTcF\]). Participants with abnormal clinically significant ECG findings is presented. It was assessed on Screening, Day 1 at pre-dose, 1, 2, 3, 4, 6, 10, 16, 24 hours and Follow-up (7 to 10 days after final discharge).

Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate measurements were recorded at each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Participants with abnormal clinically significant vital signs findings is presented. It was assessed on Screening, Day -1, 1, 2 (pre-dose, 1, 3, 4, 6, 10, 16 and 24 hours of each treatment period) and Follow-up (7 to10 days after final discharge).

The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. Blood samples for the determination of PKs was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours.

The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. Blood samples for the determination of PK was collected on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours.

The AUC 0-24 and AUC 0-t determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples for the determination of PK was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours.

An AE was defined as any untoward MO in a participant temporally associated with the use of a MP, whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

Hematology parameters included platelet count, RBC count, MCV, total neutrophils, WBC absolute, MCH, lymphocytes, MCHC, monocytes, hemoglobin, eosinophils, hematocrit, reticulocytes and basophils. It was assessed on Screening, Day -2 (can be non-fasting) and prior to breakfast (early in the morning, fasting) on Days 1, 7 and 14, and on Day 15 prior to checkout, (=24 hours post-dose) of each treatment period and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented.

Clinical chemistry parameters included BUN, potassium, AST, total and direct bilirubin, creatinine, chloride, ALT, uric acid, glucose fasting, GGT, albumin, sodium, magnesium, phosphorus inorganic, calcium, total CO2, ALP, triglycerides, total cholesterol, LDL cholesterol, free fatty acid (NEFA), HDL cholesterol and total protein. It was assessed on Screening, Day -2 (can be non-fasting) and prior to breakfast (early in the morning, fasting) on Days 1, 7 and 14, and on Day 15 prior to checkout, (=24 hours post-dose) of each treatment period and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented.

Twelve-lead ECGs was obtained in a supine position at each time point during the study using an ECG machine that automatically measured PR, QRS, QT and QTc intervals (QTcB and QTcF). Participants with abnormal clinically significant ECG findings is presented. It was assessed on Screening, on Day -1, 1, 7, 13 and 14 pre-breakfast dose (fasting) and at 1, 3, 6, 9, 12 and 24 hours of each treatment period and Follow-up (7 to 10 days after final discharge).

SBP, DBP and pulse rate measurements were recorded at each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Participants with abnormal clinically significant vital signs findings is presented. It was assessed on Screening, on Days -1 to 14 in a fasting state early in the morning (prior to morning dosing on days 1-14) and at Follow-up. On Days 1, 7, 13 and 14, it was also taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose each treatment period and Follow-up (7 to 10 days after final discharge).

The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.

The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.

The AUC0-10, AUC0-12 and AUC0-24 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For QD and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post- breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.

Ro was derived as follows: Ro = Day 13 (AUC0-24)/Day 1 (AUC0-24) for once daily dosing; Ro = Day 13 AM (AUC0-10)/Day 1 AM (AUC0-10) for BID dosing and Ro = Day 13 (AUC0-24)/Day 1 (AUC0-24) for BID dosing. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. Data presented for Day 13 and Day 14.

The AUC0-10 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post-breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.

The AUC0-24 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post-breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.

The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post-breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. Cmax for one participant from 50 BID x 14 day was not analyzed due to positive definite G Matrix.

Blood samples for the determination of insulin were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. The unit of measure is mL/min×1/micro international unit×10\^4 (mL/min×1/µIU×10\^4).

Blood samples for the determination of insulin were collected fasting pre-breakfast and then pre-morning dose (PD time 0) on Days -1, 13 and 14, and then at 10, 20, 30, 60, 90, 120, 180 min after eating the standardized breakfast meal tolerance test. For lunch (approximately 4 hour post-morning dose) samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hour post-morning dose), BID dosing groups followed the sequence of sampling, food and dosing as for breakfast (PD sample immediately before meal, eat and then dose), then 0.5, 1, 1.5, 2 and 3 hours post-dinner. A sample was also collected 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected (example: 24 hours post first-dose = pre-dose \[time 0\] for the second dose).

Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value from post-Baseline value. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated by multiplying insulin glucose index with insulin sensitivity index. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated as insulin/glucose ratio was calculated as insulin AUC(0-3\]/glucose AUC(0-3) during OGTT, while glucose/insulin ratio was calculated as glucose AUC(0-3)/insulin AUC(0-3) during OGTT. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated as insulin (30 min) - insulin (0 min)/glucose (30 min) - glucose (0 min). It was calculated as insulin (30 min) - insulin (0 min)/glucose (30 min) - glucose (0 min). The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated as 10,000/square root (\[mean plasma insulin × mean plasma glucose during OGTT or meal challenge\] × \[fasting plasma glucose × fasting plasma insulin\]). The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples were collected fasting pre-breakfast and pre-morning dose (PD time 0) on Days -1, 13 and 14 and then at 10, 20, 30, 60, 90, 120, 180 min after eating the standardized breakfast meal tolerance test. For lunch (4 hour post-morning dose) samples were collected just before the meal and after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (10 hour post-morning dose), BID dosing groups followed the sequence of sampling, food and dosing as for breakfast (PD sample immediately before meal, eat and then dose), then 0.5, 1, 1.5, 2 and 3 hours post-dinner. A sample was also collected 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value minus post-Baseline value. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.

Blood samples were collected fasting pre-breakfast and pre-morning dose (PD time 0) on Days -1, 13 and 14 and then at 10, 20, 30, 60, 90, 120, 180 min after eating the standardized breakfast meal tolerance test. For lunch (4 hour post-morning dose) samples were collected just before the meal and after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (10 hour post-morning dose), BID dosing groups followed the sequence of sampling, food and dosing as for breakfast (PD sample immediately before meal, eat and then dose), then 0.5, 1, 1.5, 2 and 3 hours post-dinner. A sample was also collected 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value minus post-Baseline value. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.