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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-002664-40 | EudraCT Number |
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Terminated due to non clinical toxicology findings and reduced safety margins.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Cohort 1 | Experimental | Cohort 1 will be 5-way crossover with 5 treatment periods. Subjects will be randomized in the ratio 4:1 to receive either single dose of GSK2983559 or placebo. |
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| Part A: Cohort 2 fasting | Experimental | Cohort 2 will be 4-way crossover design with one additional period of open-label. Subjects will be randomized in the ratio 3:1 to receive either single dose of GSK2983559 or placebo in fasted conditions |
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| Part A: Cohort 2 fed | Experimental | In Cohort 2, treatment period 5 will be open-label period. This open-label period is to determine food effect and subjects will receive GSK2983559 under fed conditions. |
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| Part B | Experimental | Part B is repeat ascending dose sequential period. There will four cohorts (3-6) of 10 healthy subjects. In each cohort subjects will be randomized to receive GSK2983559 or placebo in ratio 4:1. Subjects will receive GSK2983559 or placebo QD and twice daily dose will be decided based upon the pharmacokinetic, safety and tolerability observed in Part A. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2983559 | Drug | GSK2983559 will be available as oral capsules with dose strength of 2-45 milligram (mg), 100 and 114 mg. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | Cambridgeshire | CB2 2GG | United Kingdom |
IPD for this study is available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
A total of 85 participants were screened, of them, 54 participants were screen failures and 31 participants were enrolled and received study treatment in Part A. The study was terminated during Cohort 2 of Part A, hence no participants were enrolled in period 3, 4 and 5 (Cohort 2) of Part A and in Part B.
This was a 2-part study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK2983559 in healthy participants. The study was terminated early due to non-clinical toxicology findings and reduced safety margins. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A-Cohort 1: Placebo/GSK 4mg/GSK 10mg/GSK 30mg/GSK 100mg | Participants (Par.) received oral single dose of placebo matching GSK2983559 (GSK) in treatment period 1 followed by 4 milligram (mg) GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up (FU) visit after 14 days of last period. |
| FG001 | Part A-Cohort 1: GSK 2mg/Placebo/GSK 10mg/GSK 30mg/GSK 100mg | Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by placebo matching GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. |
| FG002 | Part A-Cohort 1: GSK 2mg/GSK 4mg/Placebo/GSK 30mg/GSK 100mg | Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by placebo matching GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. |
| FG003 | Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/Placebo/GSK 100mg | Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by placebo matching GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. |
| FG004 | Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/GSK 30mg/Placebo | Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by placebo matching GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. |
| FG005 | Part A-Cohort 2: Placebo/GSK 400mg | Participants were administered oral single dose of placebo matching GSK2983559 in treatment period 1 followed by 400 mg GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2. |
| FG006 | Part A-Cohort 2: GSK 200mg/Placebo | Participants were administered oral single dose of 200 mg GSK2983559 in treatment period 1 followed by placebo matching GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2. |
| FG007 | Part A-Cohort 2: GSK 200mg/GSK 400mg | Participants were administered oral single dose of 200 mg GSK2983559 in treatment period 1 followed by 400 mg GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2. |
| FG008 | Part B: Placebo | Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins. |
| FG009 | Part B: GSK2983559 | Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P1:PartA-Cohort1(4days)+Washout(48hours) |
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| P2:PartA-Cohort1(4days)+Washout(48hours) |
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| P3:PartA-Cohort1(4days)+Washout(48hours) |
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| P4:PartA-Cohort1(4days)+Washout(48hours) |
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| P5:PartA-Cohort1(4days)+Followup(14days) |
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| P1:PartA-Cohort2(4days)+Washout(48hours) |
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| P2:PartA-Cohort2(4days)+Followup(14days) |
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| Part B: Overall Period (11 Weeks) |
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Only data for Part A is presented as study was terminated during Part A and hence Part B was not initiated.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A-Cohort 1: Placebo/GSK 4mg/GSK 10mg/GSK 30mg/GSK 100mg | Participants (Par.) received oral single dose of placebo matching GSK2983559 (GSK) in treatment period 1 followed by 4 milligram (mg) GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up (FU) visit after 14 days of last period. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Only data for Part A is presented as study was terminated during Part A and hence Part B was not initiated. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
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| Primary | 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. | Safety Population comprised of all randomized participants who received at least one dose of study treatment. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to 7 weeks |
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Non-SAEs and SAEs were reported from start of study treatment (Day 1) up to Week 7 for Part A
Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise. Data is presented for Part A only as data was not collected in Part B due to the study was terminated during Part A, and Part B was not initiated. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A: Placebo | All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 24, 2018 | Apr 30, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 25, 2019 | Apr 30, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| ID | Term |
|---|---|
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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| Placebo | Drug | Placebo oral capsules matching GSK2983559 will be available for subjects. |
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| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline and Up to 11 weeks |
| 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. | 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. | 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. | 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. | 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 GSK2983559 | Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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 |
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| BG001 | Part A-Cohort 1: GSK 2mg/Placebo/GSK 10mg/GSK 30mg/GSK 100mg | Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by placebo matching GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. |
| BG002 | Part A-Cohort 1: GSK 2mg/GSK 4mg/Placebo/GSK 30mg/GSK 100mg | Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by placebo matching GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. |
| BG003 | Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/Placebo/GSK 100mg | Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by placebo matching GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. |
| BG004 | Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/GSK 30mg/Placebo | Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by placebo matching GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. |
| BG005 | Part A-Cohort 2: Placebo/GSK 400mg | Participants were administered oral single dose of placebo matching GSK2983559 in treatment period 1 followed by 400 mg GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2. |
| BG006 | Part A-Cohort 2: GSK 200mg/ Placebo | Participants were administered oral single dose of 200 mg GSK2983559 in treatment period 1 followed by placebo matching GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2. |
| BG007 | Part A-Cohort 2: GSK 200mg/GSK 400mg | Participants were administered oral single dose of 200 mg GSK2983559 in treatment period 1 followed by 400 mg GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2. |
| BG008 | Part B: Placebo | Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins. |
| BG009 | Part B: GSK2983559 | Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins. |
| BG010 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Only data for Part A is presented as study was terminated during Part A and hence Part B was not initiated. | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Only data for Part A is presented as study was terminated during Part A and hence Part B was not initiated. | Count of Participants | Participants |
|
All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule. |
| OG001 | Part A-Cohort 1: GSK2983559 2 mg | All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. |
| OG002 | Part A-Cohort 1: GSK2983559 4 mg | All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. |
| OG003 | Part A-Cohort 1: GSK2983559 10 mg | All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. |
| OG004 | Part A-Cohort 1: GSK2983559 30 mg | All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. |
| OG005 | Part A-Cohort 1: GSK2983559 100 mg | All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. |
| OG006 | Part A-Cohort 2: GSK2983559 200 mg | All participants received single oral dose of 200 mg GSK2983559 in Period 1. |
| OG007 | Part A-Cohort 2: GSK2983559 400 mg | All participants received single oral dose of 400 mg GSK2983559 in Period 2. |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to 7 weeks |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. Data is presented treatment-wise. Only those clinical chemistry parameters with PCI values have been presented. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to 7 weeks |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to 7 weeks |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24 and 48 hours post-dose |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to 7 weeks |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to 7 weeks |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to 7 weeks |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to 7 weeks |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. This analysis was not planned and data was not collected and not captured in the database. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to 7 weeks |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Up to 11 weeks |
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| Primary | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Mean | Standard Deviation | Seconds | Baseline (Day 1, Pre-dose), 24 and 48 hours post-dose |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Baseline and Up to 11 weeks |
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| Primary | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Mean | Standard Deviation | Ratio | Baseline (Day 1, Pre-dose), 24 and 48 hours |
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| Primary | 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. | Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | Baseline and Up to 11 weeks |
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| Secondary | 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. | Pharmacokinetic Population comprised of all participants in the safety population who had at least 1 non-missing pharmacokinetic assessment. Only those participants with data available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | 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 |
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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | 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 |
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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | 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 |
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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter | 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 |
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| Secondary | 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. | Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms per milliliter | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms per milliliter | 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 |
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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms per milliliter | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms per milliliter | 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 |
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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
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| Secondary | 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. | Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. | Posted | Median | Full Range | Hours | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Median | Full Range | Hours | 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 |
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| Secondary | 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. | Pharmacokinetic Population | Posted | Median | Full Range | Hours | 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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| Secondary | 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. | Pharmacokinetic Population | Posted | Median | Full Range | Hours | 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 |
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| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
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| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
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| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | Part B: Cmax for GSK2983559 on Day 14 | Blood samples were planned to be collected to measure Cmax at indicated time-points. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | Part B: Tmax for GSK2983559 on Day 14 | Blood samples were planned to be collected to measure Tmax at indicated time-points. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | Part B: T1/2 for GSK2983559 on Day 14 | Blood samples were planned to be collected to measure T1/2 at indicated time-points. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| Secondary | 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. | Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A. | Posted | 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 |
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| 6 |
| 16 |
| EG001 | Part A-Cohort 1: GSK2983559 2 mg | All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. | 0 | 8 | 0 | 8 | 2 | 8 |
| EG002 | Part A-Cohort 1: GSK2983559 4 mg | All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. | 0 | 8 | 0 | 8 | 2 | 8 |
| EG003 | Part A-Cohort 1: GSK2983559 10 mg | All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. | 0 | 8 | 0 | 8 | 1 | 8 |
| EG004 | Part A-Cohort 1: GSK2983559 30 mg | All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. | 0 | 8 | 0 | 8 | 1 | 8 |
| EG005 | Part A-Cohort 1: GSK2983559 100 mg | All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule. | 0 | 8 | 0 | 8 | 2 | 8 |
| EG006 | Part A-Cohort 2: GSK2983559 200 mg | All participants received single oral dose of 200 mg GSK2983559 in Period 1. | 0 | 9 | 0 | 9 | 4 | 9 |
| EG007 | Part A-Cohort 2: GSK2983559 400 mg | All participants received single oral dose of 400 mg GSK2983559 in Period 2. | 0 | 9 | 0 | 9 | 4 | 9 |
| Tooth abscess | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Respiratory tract irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Capillaritis | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Catheter site erythema | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Vessel puncture site pain | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Liver function test increased | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
|
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
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.
| Hematocrit, To within range or no change |
|
| Hematocrit, To high |
|
| Hemoglobin, To low |
|
| Hemoglobin, To within range or no change |
|
| Hemoglobin, To high |
|
| Lymphocytes, To low |
|
| Lymphocytes, To within range or no change |
|
| Lymphocytes, To high |
|
| Platelet count, To low |
|
| Platelet count, To within range or no change |
|
| Platelet count, To high |
|
| Total Neutrophils, To low |
|
| Total Neutrophils, To within range or no change |
|
| Total Neutrophils, To high |
|
| WBC count, To low |
|
| WBC count, To within range or no change |
|
| WBC count, To high |
|
| ALT, To within range or no change |
|
| ALT, To high |
|
| Albumin, To low |
|
| Albumin, To within range or no change |
|
| Albumin, To high |
|
| ALP, To low |
|
| ALP, To within range or no change |
|
| ALP, To high |
|
| AST, To low |
|
| AST, To within range or no change |
|
| AST, To high |
|
| Calcium, To low |
|
| Calcium, To within range or no change |
|
| Calcium, To high |
|
| Creatinine, To low |
|
| Creatinine, To within range or no change |
|
| Creatinine, To high |
|
| Glucose, To low |
|
| Glucose, To within range or no change |
|
| Glucose, To high |
|
| Potassium, To low |
|
| Potassium, To within range or no change |
|
| Potassium, To high |
|
| Sodium, To low |
|
| Sodium, To within range or no change |
|
| Sodium, To high |
|
| T.bil, To low |
|
| T.bil, To within range or no change |
|
| T.bil, To high |
|
|
| Abnormal CS, 1.5 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal NCS, 2 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal CS, 2 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal NCS, 2.5 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal CS, 2.5 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal NCS, 3 hours, n=6,0,0,0,0,0,9,9 |
|
|
| Abnormal CS, 3 hours, n=6,0,0,0,0,0,9,9 |
|
|
| Abnormal NCS, 4 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal CS, 4 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal NCS, 5 hours, n=6,0,0,0,0,0,9,9 |
|
|
| Abnormal CS, 5 hours, n=6,0,0,0,0,0,9,9 |
|
|
| Abnormal NCS, 8 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal CS, 8 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal NCS, 12 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal CS, 12 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal NCS, 24 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal CS, 24 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal NCS, 48 hours, n=16,8,8,8,8,8,9,9 |
|
|
| Abnormal CS, 48 hours, n=16,8,8,8,8,8,9,9 |
|
|
| DBP, To within range or no change |
|
| DBP, To high |
|
| SBP, To low |
|
| SBP, To within range or no change |
|
| SBP, To high |
|
| To within range or no change |
|
| To high |
|
| To within range or no change |
|
| To high |
|
| To within range or no change |
|
| To high |
|
|
| APTT, 48 hours, n=16,8,8,8,8,8,8,9 |
|
|
| PT, 24 hours, n=16,8,8,7,8,8,9,9 |
|
|
| PT, 48 hours, n=16,8,8,8,8,8,8,9 |
|
|
|
| 48 hours, n=16,8,8,8,8,8,8,9 |
|
|