This study is the first administration of GSK2983559, a selective receptor interacting protein 2 (RIP2) kinase inhibitor, to humans. This will be randomized, double-blinded (sponsor open) and two part study (A and B). Part A of the study is single ascending dose crossover design with two separate cohorts (1 and 2). In Part A, 9 single dose levels will be explored. In Cohort 1, 10 healthy subjects will randomized to receive single oral doses of either GSK2983559 or placebo in a ratio of 4:1 in 5 way cross-over design with 5 treatment periods. In Cohort 2, 8 healthy subjects will be randomized to receive single oral doses of either GSK2983559 or placebo in a ratio of 3:1 in 4 way cross-overs design with 4 treatment periods. In Cohort 2 there will be an additional period (period 5-open label) for assessing GSK2983559 under fed conditions. There will be 48 hours wash-out period between each dose escalation period. Part B is repeat ascending dose sequential group design. It will contain 4 Cohorts of and dosing will be done sequential dosing. Subjects in Part B will receive once daily (QD) dose or twice daily dose (will be decided based upon the pharmacokinetic, safety and tolerability observed in Part A). There will 58 subjects involved in this study. Total duration of Part A will be approximately for 11 Weeks and Part B will be approximately for 15 Weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
31
GSK2983559 will be available as oral capsules with dose strength of 2-45 milligram (mg), 100 and 114 mg.
Placebo oral capsules matching GSK2983559 will be available for subjects.
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom
Part A: Number of Participants With Non Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
An adverse event was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement.
Time frame: Up to 7 weeks
Part B: Number of Participants With Non-SAEs and SAEs
An adverse event was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-SAEs and SAEs were planned to be collected.
Time frame: Up to 11 weeks
Part A: Number of Participants With Worst Case Hematology Parameters of Potential Clinical Importance (PCI)
Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and white blood cells (WBCs) count. PCI ranges were: hematocrit (high: \>0.54 proportion of red blood cells in blood and low: change from baseline\<0.0075); hemoglobin (high: \>180 grams per liter \[g/L\] and low: change from baseline\<25 g/L); lymphocytes (low: \<0.8 Giga cells/L); platelet count (low: \<100 Giga cells/L and high: \>550 Giga cells/L); neutrophil count (low: \<1.5 Giga cells/L); white blood cell count (low: \<3 Giga cells/L and high: \>20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Only those hematology parameters with PCI values have been presented.
Time frame: Up to 7 weeks
Part B: Number of Participants With Worst Case Hematology Parameters of PCI
Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and WBC count. PCI ranges were: hematocrit (high: \>0.54 proportion of red blood cells in blood and low: change from baseline\<0.0075); hemoglobin (high: \>180 grams per liter \[g/L\] and low: change from baseline\<25 g/L); lymphocytes (low: \<0.8 Giga cells/L); platelet count (low: \<100 Giga cells/L and high: \>550 Giga cells/L); neutrophil count (low: \<1.5 Giga cells/L); white blood cell count (low: \<3 Giga cells/L and high: \>20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants with worst case hematology parameters of PCI were planned to be collected.
Time frame: Up to 11 weeks
Part A: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI
Clinical chemistry parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin (T.bil). PCI ranges were: ALT, AST, ALP (high): \>=2\*Upper limit of Normal(ULN) units per liter(U/L), albumin(low): 30 g/L, calcium: \<2(low) or \>2.75 millimoles per liter (mmol/L)(high), creatinine (high): increase from Baseline \>44.2 micromoles per liter(µmol/L), glucose: \<3(low) or \>9 mmol/L(high), potassium: \<3(low) or \>5.5 mmol/L(high), sodium: \<130(low) or \>150 mmol/L(high) and T.bil(high): \>=1.5\*ULN (µmol/L). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
Time frame: Up to 7 weeks
Part B: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI
Clinical chemistry parameters included ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were ALT(high): \>=2\*ULN U/L, albumin(low): 30 g/L, alkaline phosphatase(high): \>=2\*ULN U/L, AST(high): \>=2\*ULN U/L, calcium: \<2(low) or \>2.75 mmol/L (high), creatinine (high): increase from Baseline \>44.25 µmol/L, glucose: \<3(low) or \>9 mmol/L(high), potassium: \<3(low) or \>5.5 mmol/L(high), sodium: \<130(low) or \>150 mmol/L(high) and total bilirubin(high): \>=1.5\*ULN (µmol/L). Participants with worst case clinical chemistry parameters of PCI were planned to be collected.
Time frame: Up to 11 weeks
Part A: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Baseline was defined as latest predose (Day 1) assessment with a non-missing value.
Time frame: Up to 7 weeks
Part B: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine analysis included assessment of glucose, ketones, occult blood and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner. Baseline was defined as latest predose (Day 1) assessment with a non-missing value. Participants with worst case any increase in urinalysis results post-Baseline relative to Baseline were planned to be collected.
Time frame: Up to 11 weeks
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
12-lead ECGs were obtained using an ECG machine. Only those participants who had any abnormal ECG findings are presented. Abnormal ECG findings were categorized as clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24 and 48 hours post-dose
Part B: Number of Participants With Abnormal ECG Findings
12-lead ECGs were planned to be obtained using an ECG machine. Abnormal ECG findings were categorized as CS and NCS abnormal ECG findings. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Participants with any abnormal ECG findings were planned to be evaluated.
Time frame: Up to 11 weeks
Part A: Number of Participants With Worst Case Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Values of PCI
DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: \<45 millimeters of mercury (mmHg) (lower) and \>100 mmHg (higher) and SBP: \<85 mmHg (lower) and \>160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
Time frame: Up to 7 weeks
Part B: Number of Participants With Worst Case DBP and SBP Values of PCI
DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: \<45 mmHg (lower) and \>100 mmHg (higher) and SBP: \<85 mmHg (lower) and \>160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants with worst case DBP and SBP values of PCI were planned to be evaluated.
Time frame: Up to 11 weeks
Part A: Number of Participants With Worst Case Respiration Rate Values of PCI
Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included \<=8 breaths per minute (lower) and \>=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
Time frame: Up to 7 weeks
Part B: Number of Participants With Worst Case Respiration Rate Values of PCI
Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included \<=8 breaths per minute (lower) and \>=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants with worst case respiratory rate values of PCI were planned to be evaluated.
Time frame: Up to 11 weeks
Part A: Number of Participants With Worst Case Heart Rate Values of PCI
Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included \<40 beats per minute (lower) and \>110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
Time frame: Up to 7 weeks
Part B: Number of Participants With Worst Case Heart Rate Values of PCI
Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included \<40 beats per minute (lower) and \>110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants with worst case heart rate values of PCI were planned to be evaluated.
Time frame: Up to 11 weeks
Part A: Number of Participants With Worst Case Body Temperature Values of PCI
Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included \<=35.5 degrees Celsius (lower) and \>=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
Time frame: Up to 7 weeks
Part B: Number of Participants With Worst Case Body Temperature Values of PCI
Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included \<=35.5 degrees Celsius (lower) and \>=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants with worst case body temperature values of PCI were planned to be evaluated.
Time frame: Up to 11 weeks
Part A: Number of Participants With Abnormal Findings in Physical Examination
Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. This analysis was not planned and data was not collected and not captured in the database.
Time frame: Up to 7 weeks
Part B: Number of Participants With Abnormal Findings in Physical Examination
Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. Data was not collected and not captured in the database.
Time frame: Up to 11 weeks
Part A: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points
Blood samples were collected to evaluate activated partial thromboplastin time (APTT) and prothrombin time (PT) at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1, Pre-dose), 24 and 48 hours post-dose
Part B: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points
Blood samples were planned to be collected to evaluate PTT and PT at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline and Up to 11 weeks
Part A: Change From Baseline in International Normalized Ratio at Indicated Time Points
Blood samples were collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1, Pre-dose), 24 and 48 hours
Part B: Change From Baseline in International Normalized Ratio at Indicated Time Points
Blood samples were planned to be collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline and Up to 11 weeks
Part A (Cohort 1): Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2983559
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-t) for GSK2983559
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): AUC From Time Zero to Infinity (AUC[0-inf]) for GSK2983559
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
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Part A (Cohort 2): AUC(0-inf) for GSK2983559
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Maximum Plasma Concentration (Cmax) for GSK2983559
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Cmax for GSK2983559
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Cmax for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Terminal Elimination Half-life (T1/2) for GSK2983559
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): T1/2 for GSK2983559
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): T1/2 for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Time to Cmax (Tmax) for GSK2983559
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Tmax for GSK2983559
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Tmax for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC(0-t) for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-t) for GSK2983559 on Day 14
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC From 0 Hours to the Time of Next Dosing AUC(0-tau) for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-tau) for GSK2983559 on Day 14
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Cmax for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure Cmax at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Cmax for GSK2983559 on Day 14
Blood samples were planned to be collected to measure Cmax at indicated time-points.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure Cmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure Cmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Tmax for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure Tmax at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Tmax for GSK2983559 on Day 14
Blood samples were planned to be collected to measure Tmax at indicated time-points.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure Tmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure Tmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: T1/2 for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure T1/2 at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: T1/2 for GSK2983559 on Day 14
Blood samples were planned to be collected to measure T1/2 at indicated time-points.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure T1/2 at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure T1/2 at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Accumulation Ratio of GSK2983559
Blood samples were planned to be collected to measure accumulation ratio at indicated time-points. Accumulation ratio was to be calculated as ratio of AUC(0-tau) at Day 14 to AUC(0-tau) at Day 1.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Accumulation Ratio of GSK2668176 (Active Moiety of GSK2983559)
Blood samples were planned to be collected to measure accumulation ratio at indicated time-points. Accumulation ratio was to be calculated as ratio of AUC(0-tau) at Day 14 to AUC(0-tau) at Day 1. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC (0-t) for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure AUC(0-t) in fasted condition (Period 4) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): AUC(0-t) for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure AUC(0-t) in fed condition (Period 5) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure AUC(0-t) in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure AUC(0-t) in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): AUC(0-inf) for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure AUC(0-inf) in fasted condition (Period 4) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): AUC(0-inf) for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure AUC(0-inf) in fed condition (Period 5) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure AUC(0-inf) in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure AUC(0-inf) in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): Cmax for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure Cmax in fasted condition (Period 4) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): Cmax for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure Cmax in fed condition (Period 5) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure Cmax in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure Cmax in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): Tmax for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure Tmax in fasted condition (Period 4) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): Tmax for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure Tmax in fed condition (Period 5) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure Tmax in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure Tmax in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): T1/2 for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure T1/2 in fasted condition (Period 4) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): T1/2 for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure T1/2 in fed condition (Period 5) at indicated time-points.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure T1/2 in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure T1/2 in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5