First Time in Human (FTIH) Safety and Pharmacokinetics (PK) Study of GSK3036656 in Healthy Subjects

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT03075410

Collaborator

(none)

Enrollment

Locations

Arms

4.1

Actual Duration (Months)

Patients Per Site

3.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

GSK3036656 is being developed by GSK for the treatment of tuberculosis (TB). This is the FTIH study for GSK3036656 to evaluate the safety, tolerability and PK of single ascending and repeat oral doses of GSK3036656 in healthy adult subjects. The results of this study are intended to be used to identify appropriate and well-tolerated doses of GSK3036656 to be used in further studies. A food effect assessment will also be undertaken to investigate the influence of food on the PK of GSK3036656. The study will be conducted in two parts: Part A (single dose) and Part B (repeat dose). Up to two cohorts will be included in Part A. 9 healthy adult subjects will be included in each cohort. Each cohort will participate in up to 4 treatment (dosing) periods including a food effect treatment period. During each treatment period, GSK3036656 will be administered to 6 subjects and placebo will be administered to 3 subjects. The starting dose in Part A will be 5 milligrams (mg), and the maximum dose will be 1500 mg. The two cohorts in Part A will be dosed sequentially (i.e., dosing in Cohort 2 starts after dosing in Cohort 1 is completed). Initially, there will be a 14 day wash out period for individual subjects between each dose level. Study progression to Part B from Part A will be based on an acceptable safety, tolerability and PK profile in Part A. Part B will comprise up to 4 cohorts (Cohorts 3, 4, 5, and 6) each containing 10 (8 active: 2 placebo) healthy adult subjects to examine the safety, tolerability and PK of a repeated daily dose of GSK3036656 over a period of up to 14 days. Appropriate doses and dose regimens for Part B will be selected based on available safety, tolerability and PK data from Part A and/or any preceding repeat dose cohorts from Part B. Dividing the total daily dose into 2 or 3 smaller doses may be done in both Part A and Part B. Up to 18 subjects will be enrolled into Part A and up to 40 subjects will be enrolled into Part B. The total duration of the study for each subject recruited into Part A and Part B will be approximately 12 weeks and 8 weeks, respectively.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Drug: GSK3036656 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Double Blind, Placebo-controlled First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of GSK3036656 in Healthy Adult Volunteers

Actual Study Start Date :

Apr 2, 2017

Actual Primary Completion Date :

Aug 4, 2017

Actual Study Completion Date :

Aug 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1- GSK3036656 in Part A During Part A (Cohort 1), Subjects will receive a single dose of GSK3036656 in the morning on Day 1 in each of the 4 treatment (dosing) periods after an overnight fast of at least 8 hours. Dosing with food may also be done in Part A once results from the food effect analysis are available. The total daily dose for the treatment (dosing) period may also be divided into 2 or 3 smaller doses administered within 24 hours on discretion of the GSK study team and the principal investigator. The starting dose in Part A will be 5 mg and will then be escalated up to a dose no higher than 1500 mg. One of the 4 dosing periods will be food effect group which will be determined based on from previous cohorts. For the food effect assessment, the selected dose will be given with a high fat meal. There will be a 2 week washout between doses initially but the washout period may be modified depending on emerging data from previous cohorts. Subjects will be followed up to 2 weeks from the last dose.	Drug: GSK3036656 GSK3036656 is available as capsules (for oral administration) containing 5 mg, 25 mg or 100 mg of GSK3036656 as free base equivalent.
Placebo Comparator: Cohort 1- Placebo in Part A During Part A (Cohort 1), Subjects will receive a single matching placebo in morning on Day 1 in each of the 4 treatment (dosing) periods after an overnight fast of at least 8 hours. Dosing with food may also be done in Part A once results from the food effect analysis are available. Placebo for the treatment (dosing) period may also be divided into 2 or 3 smaller doses administered within 24 hours in a similar manner if divided for subjects receiving active treatment in the same period. One of the 4 dosing periods will be food effect group which will be determined based on from previous cohorts. For the food effect assessment, placebo will be given with a high fat meal. There will be a 2 week washout between doses initially but the washout period may be modified depending on emerging data from previous cohorts. Subjects will be followed up to 2 weeks from the last dose.	Drug: Placebo Placebo is a matching capsule containing Avicel PH (Suitable for Pharmaceutical Use) 102, for oral administration.
Experimental: Cohort 2- GSK3036656 in Part A During Part A (Cohort 2), Subjects will receive a single dose of GSK3036656 in morning on Day 1 in each period after an overnight fast of at least 8 hours. Dosing with food may also be done once results from the food effect analysis are available. The total dose for the treatment period may also be divided into 2 or 3 smaller doses administered within 24 hours on discretion of the GSK study team and the principal investigator. The dose will be selected on basis of safety, tolerability and PK data from the previous treatment period or cohort and will then be escalated up to a dose no higher than 1500 mg. One of the 4 dosing periods will be food effect group, determined based on from previous cohorts, where the selected dose will be given with a high fat meal. There will be a 2 week washout between doses initially but the washout period may be modified depending on emerging data from previous cohorts. Subjects will be followed up to 2 weeks from the last dose.	Drug: GSK3036656 GSK3036656 is available as capsules (for oral administration) containing 5 mg, 25 mg or 100 mg of GSK3036656 as free base equivalent.
Placebo Comparator: Cohort 2- Placebo in Part A During Part A (Cohort 2), Subjects will receive a single matching placebo in morning on Day 1 in each of the 4 treatment (dosing) periods after an overnight fast of at least 8 hours. Dosing with food may also be done once results from the food effect analysis are available. Placebo for the treatment period may also be divided into 2 or 3 smaller doses administered within 24 hours in a similar manner if divided for subjects receiving active treatment in the same period. One of the 4 dosing periods will be food effect group, determined based on from previous cohorts, where the placebo will be given with a high fat meal. There will be a 2 week washout between doses initially but the washout period may be modified depending on emerging data from previous cohorts. Subjects will be followed up to 2 weeks from the last dose.	Drug: Placebo Placebo is a matching capsule containing Avicel PH (Suitable for Pharmaceutical Use) 102, for oral administration.
Experimental: Cohort 3- GSK3036656 in Part B During Part B (Cohort 3), Subjects will receive a single dose of GSK3036656 once daily in morning on Day 1 after an overnight fast of at least 8 hours. Subjects will receive repeat single dose of GSK3036656 once daily over a period of 14 days. Dosing with food may also be done if there are PK or tolerability reasons making it preferable to dose in a fed state (dose will be given with a high fat meal.). The total dose may also be divided into 2 or 3 smaller doses administered within 24 hours on discretion of the GSK study team and the principal investigator. Appropriate dose and dose regimen will be selected on available safety, tolerability and PK data from Part A. Subjects will be followed up to 2 weeks from the last dose.	Drug: GSK3036656 GSK3036656 is available as capsules (for oral administration) containing 5 mg, 25 mg or 100 mg of GSK3036656 as free base equivalent.
Placebo Comparator: Cohort 3- Placebo in Part B During Part B (Cohort 3), Subjects will receive a single matching placebo once daily in morning on Day 1 after an overnight fast of at least 8 hours. Subjects will receive a placebo once daily over a period of 14 days. Dosing with food may also be done if the active treatment is given in a fed state (dose will be given with a high fat meal.). The total dose may also be divided into 2 or 3 smaller doses administered within 24 hours in a similar manner if divided for subjects receiving active treatment in the same cohort. Subjects will be followed up to 2 weeks from the last dose.	Drug: Placebo Placebo is a matching capsule containing Avicel PH (Suitable for Pharmaceutical Use) 102, for oral administration.
Experimental: Cohort 4- GSK3036656 in Part B During Part B (Cohort 4), Subjects will receive a single dose of GSK3036656 once daily in morning on Day 1 after an overnight fast of at least 8 hours. Subjects will receive repeat single dose of GSK3036656 once daily over a period of 14 days. Dosing with food may also be done if there are PK or tolerability reasons making it preferable to dose in a fed state (dose will be given with a high fat meal.). The total dose may also be divided into 2 or 3 smaller doses administered within 24 hours on discretion of the GSK study team and the principal investigator. Appropriate dose and dose regimen will be selected on available safety, tolerability and PK data from preceding repeat dose cohorts from Part B. Subjects will be followed up to 2 weeks from the last dose.	Drug: GSK3036656 GSK3036656 is available as capsules (for oral administration) containing 5 mg, 25 mg or 100 mg of GSK3036656 as free base equivalent.
Placebo Comparator: Cohort 4- Placebo in Part B During Part B (Cohort 4), Subjects will receive a single matching placebo once daily in morning on Day 1 after an overnight fast of at least 8 hours. Subjects will receive a placebo once daily over a period of 14 days. Dosing with food may also be done if the active treatment is given in a fed state (dose will be given with a high fat meal.). The total dose may also be divided into 2 or 3 smaller doses administered within 24 hours in a similar manner if divided for subjects receiving active treatment in the same cohort. Subjects will be followed up to 2 weeks from the last dose.	Drug: Placebo Placebo is a matching capsule containing Avicel PH (Suitable for Pharmaceutical Use) 102, for oral administration.
Experimental: Cohort 5- GSK3036656 in Part B During Part B (Cohort 5), Subjects will receive a single dose of GSK3036656 once daily in morning on Day 1 after an overnight fast of at least 8 hours. Subjects will receive repeat single dose of GSK3036656 once daily over a period of 14 days. Dosing with food may also be done if there are PK or tolerability reasons making it preferable to dose in a fed state (dose will be given with a high fat meal.). The total dose may also be divided into 2 or 3 smaller doses administered within 24 hours on discretion of the GSK study team and the principal investigator. Appropriate dose and dose regimen will be selected on available safety, tolerability and PK data from preceding repeat dose cohorts from Part B. Subjects will be followed up to 2 weeks from the last dose.	Drug: GSK3036656 GSK3036656 is available as capsules (for oral administration) containing 5 mg, 25 mg or 100 mg of GSK3036656 as free base equivalent.
Placebo Comparator: Cohort 5- Placebo in Part B During Part B (Cohort 5), Subjects will receive a single matching placebo once daily in morning on Day 1 after an overnight fast of at least 8 hours. Subjects will receive a placebo once daily over a period of 14 days. Dosing with food may also be done if the active treatment is given in a fed state (dose will be given with a high fat meal.). The total dose may also be divided into 2 or 3 smaller doses administered within 24 hours in a similar manner if divided for subjects receiving active treatment in the same cohort. Subjects will be followed up to 2 weeks from the last dose.	Drug: Placebo Placebo is a matching capsule containing Avicel PH (Suitable for Pharmaceutical Use) 102, for oral administration.
Experimental: Cohort 6- GSK3036656 in Part B During Part B (Cohort 6), Subjects will receive a single dose of GSK3036656 once daily in morning on Day 1 after an overnight fast of at least 8 hours. Subjects will receive repeat single dose of GSK3036656 once daily over a period of 14 days. Dosing with food may also be done if there are PK or tolerability reasons making it preferable to dose in a fed state (dose will be given with a high fat meal.). The total dose may also be divided into 2 or 3 smaller doses administered within 24 hours on discretion of the GSK study team and the principal investigator. Appropriate dose and dose regimen will be selected on available safety, tolerability and PK data from preceding repeat dose cohorts from Part B. Subjects will be followed up to 2 weeks from the last dose.	Drug: GSK3036656 GSK3036656 is available as capsules (for oral administration) containing 5 mg, 25 mg or 100 mg of GSK3036656 as free base equivalent.
Placebo Comparator: Cohort 6- Placebo in Part B During Part B (Cohort 6), Subjects will receive a single matching placebo once daily in morning on Day 1 after an overnight fast of at least 8 hours. Subjects will receive a placebo once daily over a period of 14 days. Dosing with food may also be done if the active treatment is given in a fed state (dose will be given with a high fat meal.). The total dose may also be divided into 2 or 3 smaller doses administered within 24 hours in a similar manner if divided for subjects receiving active treatment in the same cohort. Subjects will be followed up to 2 weeks from the last dose.	Drug: Placebo Placebo is a matching capsule containing Avicel PH (Suitable for Pharmaceutical Use) 102, for oral administration.

Outcome Measures

Primary Outcome Measures

Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A [Up to 12 weeks]
An AE is 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. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above. Safety Population comprised of all randomized participants who received at least one dose of study medication.
Number of Participants With nSAE and SAEs for Part B [Up to 8 weeks]
An AE is 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. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A [Up to 6 weeks]
12-lead ECGs were collected during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) intervals. At each time point at which triplicate ECGs were required, three individual ECG tracings were obtained as closely as possible in succession, but no more than 2 to 5 minutes apart. ECG findings were categorized as normal, abnormal not clinically significant (A-NCS) and abnormal clinically significant (A-CS). Only A-NCS and A-CS worst case post-Baseline values have been presented. Only those participants with data available at the indicated time point were analyzed.
Number of Subjects With Clinically Relevant Changes in ECG in Part B [Up to 8 weeks]
12-lead ECGs were collected during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT interval and QTcF intervals. At each time point at which triplicate ECGs were required, three individual ECG tracings were obtained as closely as possible in succession, but no more than 2 to 5 minutes apart. ECG findings were categorized as normal, A-NCS and A-CS. Only A-NCS and A-CS worst case post-Baseline values have been presented.
Number of Participants With Abnormal Cardiac Telemetry Findings for Part A [25 hours for each period]
Continuous cardiac telemetry was performed from approximately 1 hour pre-dose to 24 hours post dosing . Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented.
Number of Participants With Abnormal Cardiac Telemetry Findings for Part B [25 hours for each period]
Continuous cardiac telemetry was performed from approximately 1 hour pre-dose to 24 hours post dosing . Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented.
Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A [Up to 6 weeks]
SBP and DBP were assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for SBP was less than 85 mmHg (lower) and greater than 160 mmHg (upper) while that for DBP was less than 45 mmHg (lower) and greater than 100 mmHg (upper).
Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B [Up to 8 weeks]
SBP and DBP were assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for SBP was less than 85 mmHg (lower) and greater than 160 mmHg (upper) while that for DBP was less than 45 mmHg (lower) and greater than 100 mmHg (upper).
Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part A [Up to 6 weeks]
Heart rate was assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for heart was less than 40 bpm (lower) and greater than 110 bpm (upper).
Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part B [Up to 8 weeks]
Heart rate was assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for heart was less than 40 bpm (lower) and greater than 110 bpm (upper).
Number of Participants With Vital Sign Parameter Temperature of PCI for Part A [Up to 6 weeks]
Number of participants with temperature data of PCI have been presented.
Number of Participants With Vital Sign Parameter Temperature of PCI for Part B [Up to 8 weeks]
Number of participants with temperature data of PCI have been presented.
Number of Participants With Clinical Chemistry Parameters of PCI for Part A [Up to 12 weeks]
Blood samples were collected for the assessment of clinical chemistry parameters namely blood urea nitrogen (BUN), creatinine, glucose, cholesterol, potassium, sodium, calcium, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, triglycerides, total and direct bilirubin, total protein, albumin and troponin. Only categories with PCI values have been presented, therefore only AST is presented.
Number of Participants With Clinical Chemistry Parameters of PCI for Part B [Up to 8 weeks]
Blood samples were collected for the assessment of clinical chemistry parameters namely BUN, creatinine, glucose, cholesterol, potassium, sodium, calcium, AST, ALT, alkaline phosphatase, triglycerides, total and direct bilirubin, total protein, albumin and troponin. Only categories with PCI values have been presented.
Number of Participants With Hematology Parameters of PCI for Part A [Up to 12 weeks]
Blood samples were collected for the assessment of hematology parameters platelet count, red blood cell count, hemoglobin, hematocrit, reticulocytes, mean corpuscle volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, basophils and eosinophils. Only categories with PCI values have been presented.
Number of Participants With Hematology Parameters of PCI for Part B [Up to 8 weeks]
Blood samples were collected for the assessment of hematology parameters platelet count, red blood cell count, hemoglobin, hematocrit, reticulocytes, mean corpuscle volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, basophils and eosinophils. Only categories with PCI values have been presented.
Number of Participants With Abnormal Urinalysis Parameters for Part A [Up to 72 hours post-dose]
Urinalysis included dipstick urine test which was used to screen for glucose, ketones, occult blood and protein up to 72 hours post dose. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, ketones, occult blood and protein can be read as negative, trace, trace-intact, trace-lysed,1+ and 2+ indicating proportional concentrations in the urine sample. Only categories with non-negative values have been presented. Only those participants with data available the indicated time points were analyzed.
Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A [Up to 72 hours post-dose]
Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 72 hours in Part A. Only those participants with data available at the indicated time points were analyzed.
Number of Participants With Abnormal Urinalysis Parameters for Part B [Up to 8 weeks]
Urinalysis included dipstick urine test which was used to screen for glucose, ketones, occult blood and protein up to 14 days post dose The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, ketones, occult blood and protein can be read as negative, trace, trace-intact, trace-lysed, 1+ and 2+ indicating proportional concentrations in the urine sample. Only categories with non-negative values have been presented. Only those participants available at the specified time points were analyzed represented by n=x in the category titles. Period 1 = Cohort 1 in Part B, Period 2 = Cohort 2 in Part B.
Urine pH Analysis by Dipstick Method for Part B [Up to 8 weeks]
Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 8 weeks in Part B. Only those participants available at the specified time points were analyzed represented by n=x in the category titles. Period 1 = Cohort 1 in Part B, Period 2 = Cohort 2 in Part B.
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) Following Single Dose Administration of GSK3036656 for Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 Ethylenediaminetetraacetic acid (EDTA) tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. PK population comprised of participants in the Safety population who administered at least one dose of active treatment and had at least one evaluable PK sample.
AUC From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3036656 Following Single Dose Administration for Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Cmax will be derived from the PK samples collected at the indicated time points Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Maximum Observed Plasma Drug Concentration (Cmax) of GSK3036656 Following Single Dose Administration for Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3036656 Following Single Dose Administration for Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Apparent Terminal Half-life (t1/2) of GSK3036656 Following Single Dose Administration for Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
AUC[0-t] Following Repeated Dose Administration of GSK3036656 for Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1. The actual date and time of each blood sample collection was recorded. Results presented are for Day 1.
AUC From Time Zero During a Dosing Interval of Duration Tau (AUC[0-tau]) of GSK3036656 Following Repeated Dose Administration for Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14The actual date and time of each blood sample collection was recorded. Results presented are for Day 14.
Cmax of GSK3036656 Following Repeated Dose Administration for Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. The actual date and time of each blood sample collection was recorded.
Tmax of GSK3036656 Following Repeat Dose Administration for Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. The actual date and time of each blood sample collection was recorded.
t1/2 of GSK3036656 Following Repeated Dose Administration for Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14.]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14. The actual date and time of each blood sample collection was recorded. Results presented are for Day 14.

Secondary Outcome Measures

AUC (0-t) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
AUC (0-infinity) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Cmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
t1/2 of GSK3036656 Following Single Dose Administration in Fed Condition in Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Tmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Observed Accumulation Ratio Based on AUC (AUC [Ro]) of GSK3036656 in Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14]
AUC Ro was calculated as Day 14 AUC(0-tau)/Day 1 AUC(0-t), where t and tau= 24 hours.
Observed Accumulation Ratio Based on Cmax (RCmax) of GSK3036656 in Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14]
Rcmax was calculated as Day 14 Cmax/Day 1 Cmax. Statistics has been presented on geometric least square means.
Steady State Ratio (Rss) of GSK3036656 in Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14]
Rss was calculated as Day 14 AUC (0-tau)/Day 1 AUC (0-inf). It was not possible to calculate AUC(0-inf) on Day 1 for the repeat dosing period, therefore it was not possible to calculate the (Rss).Na indicates data was not available.
Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B [Day 1 (24 hours), Day 12 (Pre-dose ), Day 13 (Pre-dose ), Day 14 (Pre-dose), Day 14 (24 hours)]
Blood samples for the analysis of Ctau were collected at Day 1 (24 hours), Day 12 (Pre-dose ), Day 13 (Pre-dose ), Day 14 (Pre-dose), Day 14 (24 hours). Ctau samples collected were used to assess attainment of steady state. Statistics has been presented on geometric least square means.
AUC (0-infinity) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for the analysis of AUC (0-infinity) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. AUC(0-infinity) following single doses was used for assessment of dose proportionality.
AUC (0-t) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for the analysis of AUC (0-t) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. AUC(0-t) following single doses was used for assessment of dose proportionality.
Cmax as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period]
Blood samples for the analysis of Cmax were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. Cmax following single doses was used for assessment of dose proportionality.
AUC (0-tau) as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13]
Blood samples for the assessment of AUC (0-tau) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. AUC (0-tau) following repeat doses was used for assessment of dose proportionality.
Cmax as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B [Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13]
Blood samples for the assessment of Cmax were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. Cmax following repeat doses was used for assessment of dose proportionality.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied, may be included only if the investigator in consultation with the medical monitor, if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight >=60 kilograms (kg) and body mass index (BMI) within the range 19 to 29.9 kg/meter^2 inclusive.
Male
Female subjects of non-child bearing potential are eligible to participate. Non-child bearing potential is defined as:
Pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or documented bilateral salpingectomy; hysterectomy; documented bilateral oophorectomy.
Postmenopausal defined as 12 months of spontaneous amenorrhea. Post-menopausal status will be confirmed by a simultaneous follicle stimulating hormone (FSH) and estradiol levels test.
Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 90 days after the last dose of study treatment (i.e. one sperm cycle).
Vasectomy with documentation of azoospermia.
Male condom plus partner use of one of the contraceptive options as follows: contraceptive subdermal implant; intrauterine device or intrauterine system; highly effective oral contraceptive, either combined or progestogen alone (provided it is associated with inhibition of ovulation); injectable progestogen; contraceptive vaginal ring; percutaneous contraceptive patches.
These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion criteria:

Alanine aminotransferase (ALT) and bilirubin >1.5 times of upper limit of normal (ULN) (isolated bilirubin >1.5 times of ULN may be acceptable, after consultation with the GlaxoSmithKline (GSK) medical monitor, if bilirubin is fractionated and direct bilirubin <35 percent)
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
QTcF >450 milliseconds.
Presence of moderate or severe valve disorder or any other clinically significant abnormality.
Subjects with a history of photosensitivity.
Females of non-childbearing potential who are susceptible to heavy periods or vaginal bleeding or spotting.
Pregnant females. A human chorionic gonadotrophin (hCG) test will be performed on Day -1 of each treatment (dosing) period in Part A and Part B for women for whom post-menopausal status has not been confirmed by FSH/estradiol testing. No pregnancy tests will be required for female subjects confirmed as post-menopausal by FSH/estradiol testing.
Lactating females.
Use of prescription or non-prescription drugs, including high-dose vitamins, herbal and dietary supplements (including Saint John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator and sponsor, the medication will not interfere with the study procedures or compromise subject safety. Paracetamol for mild analgesia will be permitted.
Breath carbon monoxide test indicative of smoking or history of current use of tobacco- or nicotine-containing products.
Current regular alcohol consumption defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
Subjects must not sunbathe or use a tanning device whilst taking the study medication and until at least 2 weeks after their last dose. Subjects are to be advised that they should wear protective clothing (e.g. sun hat, long sleeves) and use a broad spectrum ultraviolet A/ ultraviolet B sunscreen (sun protection factor >=30) when outdoors.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
A positive test for human immunodeficiency virus (HIV) antibody.
A positive pre-study drug/alcohol screen.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	London		United Kingdom	NW10 7EW
2	GSK Investigational Site	London		United Kingdom	NW10 7

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Director: GSK Clinical Trials, GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT03075410

Other Study ID Numbers:

201040
2015-003654-41

First Posted:

Mar 9, 2017

Last Update Posted:

Apr 19, 2019

Last Verified:

Jan 1, 2019

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by GlaxoSmithKline

Additional relevant MeSH terms:

Tuberculosis

GSK656

Study Results

Participant Flow

Recruitment Details	This was a double blind, placebo-controlled study to evaluate the safety, tolerability and pharmacokinetics (PK) of single and repeat doses of GSK3036656 in healthy adult participants. The study was conducted at 1 center in United Kingdom from 02-April-2017 to 04-August-2017. Part A was a crossover design, Part B was a parallel group design..
Pre-assignment Detail	20 participants screened, 8 were screen failures (SF). 9 were randomized at the beginning of Part A. During Part A, 2 of the 3 participants who withdrew were replaced, hence 11 randomized. 30 participants screened, 7 were SF, 4 passed screening but were kept in reserve, hence 19 randomized in Part B.

Arm/Group Title	PartA - Placebo/15 mg/25 mg/5 mg (Fed)	PartA - Placebo/15 mg/25 mg/Placebo	PartA - 5 mg/Placebo/25 mg/5 mg (Fed)	PartA - 5 mg/Placebo/25 mg/Placebo	PartA - 5 mg/15 mg/Placebo/5 mg (Fed)	PartA - 5 mg/15 mg/Placebo/Placebo	Part B-Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to GSK3036656 5 milligrams (mg) followed by GSK3036656 15 mg followed by GSK3036656 25 mg followed by GSK3036656 5 mg (fed) capsules orally for 14 Days.	Participants received matching placebo to GSK3036656 5 mg followed by GSK3036656 15 mg followed by GSK3036656 25 mg followed by matching placebo to GSK3036656 5 mg capsules orally for 14 Days.	Participants received SK3036656 5 mg followed by matching placebo to GSK3036656 5 mg followed by GSK3036656 25 mg followed by GSK3036656 5 mg (fed) capsules orally for 14 Days.	Participants received SK3036656 5 mg followed by matching placebo to GSK3036656 5 mg followed by GSK3036656 25 mg followed by matching placebo to GSK3036656 5 mg capsules orally for 14 Days.	Participants received GSK3036656 5 mg followed by GSK3036656 15 mg followed by matching placebo to GSK3036656 5 mg followed by GSK3036656 5 mg (fed) capsules orally for 14 Days.	Participants received GSK3036656 5 mg followed by GSK3036656 15 mg followed by matching placebo to GSK3036656 5 mg followed by matching placebo to GSK3036656 5 mg capsules orally for 14 Days.	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Period Title: Part A-Period 1 (14 Days)
STARTED	2	1	2	1	2	1	0	0	0
COMPLETED	2	1	2	1	2	1	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Part A-Period 1 (14 Days)
STARTED	2	1	2	1	2	1	0	0	0
COMPLETED	2	1	2	1	2	1	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Part A-Period 1 (14 Days)
STARTED	2	1	2	1	2	1	0	0	0
COMPLETED	1	1	1	1	2	1	0	0	0
NOT COMPLETED	1	0	1	0	0	0	0	0	0
Period Title: Part A-Period 1 (14 Days)
STARTED	1	1	1	1	2	1	0	0	0
COMPLETED	1	1	1	1	2	1	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Part A-Period 1 (14 Days)
STARTED	2	1	2	1	2	1	0	0	0
COMPLETED	1	1	2	1	2	1	0	0	0
NOT COMPLETED	1	0	0	0	0	0	0	0	0
Period Title: Part A-Period 1 (14 Days)
STARTED	1	1	2	1	2	1	0	0	0
COMPLETED	1	1	2	1	2	1	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Part A-Period 1 (14 Days)
STARTED	1	1	2	1	2	1	0	0	0
COMPLETED	1	1	2	1	2	1	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Part A-Period 1 (14 Days)
STARTED	0	0	0	0	0	0	4	7	8
COMPLETED	0	0	0	0	0	0	4	7	8
NOT COMPLETED	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part A - Placebo/15 mg/25 mg/5 mg (Fed)	Part A - Placebo/15 mg/25 mg/Placebo	Part A - 5 mg/Placebo/25 mg/5 mg (Fed)	Part A - 5 mg/Placebo/25 mg/Placebo	Part A - 5 mg/15 mg/Placebo/5 mg (Fed)	Part A - 5 mg/15 mg/Placebo/Placebo	Part B-Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg	Total
Arm/Group Description	Participants received matching placebo to GSK3036656 5 mg followed by GSK3036656 15 mg followed by GSK3036656 25 mg followed by GSK3036656 5 mg (fed) capsules orally for 14 Days.	Participants received matching placebo to GSK3036656 5 mg followed by GSK3036656 15 mg followed by GSK3036656 25 mg followed by matching placebo to GSK3036656 5 mg capsules orally for 14 Days.	Participants received SK3036656 5 mg followed by matching placebo to GSK3036656 5 mg followed by GSK3036656 25 mg followed by GSK3036656 5 mg (fed) capsules orally for 14 Days.	Participants received SK3036656 5 mg followed by matching placebo to GSK3036656 5 mg followed by GSK3036656 25 mg followed by matching placebo to GSK3036656 5 mg capsules orally for 14 Days.	Participants received GSK3036656 5 mg followed by GSK3036656 15 mg followed by matching placebo to GSK3036656 5 mg followed by GSK3036656 5 mg (fed) capsules orally for 14 Days.	Participants received GSK3036656 5 mg followed by GSK3036656 15 mg followed by matching placebo to GSK3036656 5 mg followed by matching placebo to GSK3036656 5 mg capsules orally for 14 Days.	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.	Total of all reporting groups
Overall Participants	3	1	3	1	2	1	4	7	8	30
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	33.7 (5.03)	25 (NA)	26.3 (2.52)	28.0 (NA)	34.0 (1.41)	50.0 (NA)	30.3 (9.43)	31.9 (6.26)	35.1 (7.88)	32.5 (7.39)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	1 100%	0 0%	0 0%	0 0%	1 3.3%
Male	3 100%	1 100%	3 100%	1 100%	2 100%	0 0%	4 100%	7 100%	8 100%	29 96.7%
Race/Ethnicity, Customized (Count of Participants)
American Indian/Alaskan Native	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 3.3%
Asian-South Asian Heritage	0 0%	0 0%	0 0%	0 0%	1 50%	0 0%	1 25%	0 0%	0 0%	2 6.7%
Black/ African American	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	0 0%	2 6.7%
White-White/Caucasian/European Heritage	1 33.3%	1 100%	3 100%	1 100%	1 50%	1 100%	2 50%	5 71.4%	8 100%	23 76.7%
Unknown	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	1 14.3%	0 0%	2 6.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Non-serious Adverse Events (nSAE) and Serious Adverse Events (SAEs) for Part A
Description	An AE is 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. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above. Safety Population comprised of all randomized participants who received at least one dose of study medication.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part A

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
nSAE	1 33.3%	1 100%	1 33.3%	3 300%	1 50%
SAE	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With nSAE and SAEs for Part B
Description	An AE is 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. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part B

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
nSAE	0 0%	2 200%	1 33.3%
SAE	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings for Part A
Description	12-lead ECGs were collected during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) intervals. At each time point at which triplicate ECGs were required, three individual ECG tracings were obtained as closely as possible in succession, but no more than 2 to 5 minutes apart. ECG findings were categorized as normal, abnormal not clinically significant (A-NCS) and abnormal clinically significant (A-CS). Only A-NCS and A-CS worst case post-Baseline values have been presented. Only those participants with data available at the indicated time point were analyzed.
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
A-NCS	2 66.7%	1 100%	0 0%	0 0%	0 0%
A-CS	0 0%	0 0%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Number of Subjects With Clinically Relevant Changes in ECG in Part B
Description	12-lead ECGs were collected during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT interval and QTcF intervals. At each time point at which triplicate ECGs were required, three individual ECG tracings were obtained as closely as possible in succession, but no more than 2 to 5 minutes apart. ECG findings were categorized as normal, A-NCS and A-CS. Only A-NCS and A-CS worst case post-Baseline values have been presented.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part A

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
A-NCS	1 33.3%	3 300%	3 100%
A-CS	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Participants With Abnormal Cardiac Telemetry Findings for Part A
Description	Continuous cardiac telemetry was performed from approximately 1 hour pre-dose to 24 hours post dosing . Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented.
Time Frame	25 hours for each period

Outcome Measure Data

Analysis Population Description
Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Number of Participants With Abnormal Cardiac Telemetry Findings for Part B
Description	Continuous cardiac telemetry was performed from approximately 1 hour pre-dose to 24 hours post dosing . Number of participants who had abnormal findings upon cardiac telemetry assessment have been presented.
Time Frame	25 hours for each period

Outcome Measure Data

Analysis Population Description
Safety Population for Part B

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
Count of Participants [Participants]	0 0%	0 0%	0 0%

7. Primary Outcome

Title	Number of Participants With Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance (PCI) for Part A
Description	SBP and DBP were assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for SBP was less than 85 mmHg (lower) and greater than 160 mmHg (upper) while that for DBP was less than 45 mmHg (lower) and greater than 100 mmHg (upper).
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
SBP	0 0%	0 0%	0 0%	0 0%	0 0%
DBP	0 0%	0 0%	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Number of Participants With Vital Sign Parameters SBP and DBP of PCI for Part B
Description	SBP and DBP were assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for SBP was less than 85 mmHg (lower) and greater than 160 mmHg (upper) while that for DBP was less than 45 mmHg (lower) and greater than 100 mmHg (upper).
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part B

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
SBP	0 0%	0 0%	0 0%
DBP	0 0%	0 0%	1 33.3%

9. Primary Outcome

Title	Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part A
Description	Heart rate was assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for heart was less than 40 bpm (lower) and greater than 110 bpm (upper).
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

10. Primary Outcome

Title	Number of Participants With Vital Sign Parameter Heart Rate of PCI for Part B
Description	Heart rate was assessed in supine position with a completely automated device. Measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). The PCI range for heart was less than 40 bpm (lower) and greater than 110 bpm (upper).
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part B

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
Count of Participants [Participants]	0 0%	0 0%	0 0%

11. Primary Outcome

Title	Number of Participants With Vital Sign Parameter Temperature of PCI for Part A
Description	Number of participants with temperature data of PCI have been presented.
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

12. Primary Outcome

Title	Number of Participants With Vital Sign Parameter Temperature of PCI for Part B
Description	Number of participants with temperature data of PCI have been presented.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part B

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
Count of Participants [Participants]	0 0%	0 0%	0 0%

13. Primary Outcome

Title	Number of Participants With Clinical Chemistry Parameters of PCI for Part A
Description	Blood samples were collected for the assessment of clinical chemistry parameters namely blood urea nitrogen (BUN), creatinine, glucose, cholesterol, potassium, sodium, calcium, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, triglycerides, total and direct bilirubin, total protein, albumin and troponin. Only categories with PCI values have been presented, therefore only AST is presented.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	1 50%

14. Primary Outcome

Title	Number of Participants With Clinical Chemistry Parameters of PCI for Part B
Description	Blood samples were collected for the assessment of clinical chemistry parameters namely BUN, creatinine, glucose, cholesterol, potassium, sodium, calcium, AST, ALT, alkaline phosphatase, triglycerides, total and direct bilirubin, total protein, albumin and troponin. Only categories with PCI values have been presented.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part B

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
ALT	0 0%	1 100%	0 0%
AST	0 0%	1 100%	0 0%

15. Primary Outcome

Title	Number of Participants With Hematology Parameters of PCI for Part A
Description	Blood samples were collected for the assessment of hematology parameters platelet count, red blood cell count, hemoglobin, hematocrit, reticulocytes, mean corpuscle volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, basophils and eosinophils. Only categories with PCI values have been presented.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

16. Primary Outcome

Title	Number of Participants With Hematology Parameters of PCI for Part B
Description	Blood samples were collected for the assessment of hematology parameters platelet count, red blood cell count, hemoglobin, hematocrit, reticulocytes, mean corpuscle volume, mean corpuscular hemoglobin, neutrophils, lymphocytes, monocytes, basophils and eosinophils. Only categories with PCI values have been presented.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part B

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
Leukocytes	0 0%	1 100%	0 0%
Neutrophils	0 0%	1 100%	1 33.3%

17. Primary Outcome

Title	Number of Participants With Abnormal Urinalysis Parameters for Part A
Description	Urinalysis included dipstick urine test which was used to screen for glucose, ketones, occult blood and protein up to 72 hours post dose. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, ketones, occult blood and protein can be read as negative, trace, trace-intact, trace-lysed,1+ and 2+ indicating proportional concentrations in the urine sample. Only categories with non-negative values have been presented. Only those participants with data available the indicated time points were analyzed.
Time Frame	Up to 72 hours post-dose

Outcome Measure Data

Analysis Population Description
Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
Day -1, Ketone, Trace	1 33.3%	0 0%	1 33.3%	0 0%	0 0%
Day -1, Occult blood, 1+	0 0%	0 0%	0 0%	0 0%	1 50%
Day -1, Occult blood, 2+	0 0%	0 0%	1 33.3%	0 0%	0 0%
Day -1, Occult blood, trace-intact	1 33.3%	0 0%	0 0%	0 0%	0 0%
Day -1, Occult blood, trace-lysed	1 33.3%	0 0%	0 0%	0 0%	0 0%
Day -1, Protein, Trace	1 33.3%	0 0%	2 66.7%	0 0%	1 50%
24 hours, Ketones, 2+	1 33.3%	0 0%	0 0%	0 0%	0 0%
24 hours, Occult blood, 2+	0 0%	0 0%	1 33.3%	0 0%	0 0%
24 hours, Occult blood, trace-intact	1 33.3%	0 0%	0 0%	0 0%	0 0%
24 hours, Occult blood, trace-lysed	1 33.3%	0 0%	0 0%	0 0%	0 0%
72 hours, Ketone, Trace	0 0%	0 0%	1 33.3%	0 0%	0 0%
72 hours, Occult blood, 1+	1 33.3%	0 0%	1 33.3%	0 0%	0 0%
72 hours, Occult blood, trace-intact	0 0%	0 0%	0 0%	0 0%	1 50%
72 hours, Occult blood, trace-lysed	0 0%	0 0%	0 0%	1 100%	0 0%
72 hours, Protein, Trace	2 66.7%	0 0%	0 0%	0 0%	0 0%

18. Primary Outcome

Title	Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part A
Description	Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 72 hours in Part A. Only those participants with data available at the indicated time points were analyzed.
Time Frame	Up to 72 hours post-dose

Outcome Measure Data

Analysis Population Description
Safety Population for Part A. For arm Part A-Matching Placebo 3 of the 9 placebo participants received placebo twice, therefore they had these measures done in 2 different treatment periods, so N=9 but number of units analyzed=12.

Arm/Group Title	Part A-Matching Placebo	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	9	6	6	6	5
pH at Day -1	6.08 (0.469)	6.00 (0.548)	5.50 (0.548)	5.92 (0.492)	6.70 (1.483)
pH at 24 hours	6.04 (0.498)	6.50 (0.447)	5.83 (0.258)	6.08 (0.204)	6.80 (1.095)
pH at 72 hours	6.46 (0.753)	6.00 (1.095)	5.92 (0.492)	6.42 (0.665)	7.30 (0.671)

19. Primary Outcome

Title	Number of Participants With Abnormal Urinalysis Parameters for Part B
Description	Urinalysis included dipstick urine test which was used to screen for glucose, ketones, occult blood and protein up to 14 days post dose The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, ketones, occult blood and protein can be read as negative, trace, trace-intact, trace-lysed, 1+ and 2+ indicating proportional concentrations in the urine sample. Only categories with non-negative values have been presented. Only those participants available at the specified time points were analyzed represented by n=x in the category titles. Period 1 = Cohort 1 in Part B, Period 2 = Cohort 2 in Part B.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part B

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
Day -1, Ketones, Trace,n=2,7,0	0 0%	1 100%
Day -1, Occult blood,Trace-intact,n=2,7,0	1 33.3%	0 0%
Day 14, Ketones, Trace,n=2,7,0	0 0%	1 100%
Day 14, protein, 1+,n=2,7,0	0 0%	1 100%
Day -1,Occult blood,Trace-intact,n=2,0,8	1 33.3%	2 200%
Day 6,Occult blood,Trace-intact,n=2,0,8	0 0%	1 100%
Day 6,Occult blood,Trace-lysed,n=2,0,8	0 0%	2 200%
Day 10, Ketones, Trace,n=2,0,8	0 0%	1 100%
Day 14, Protein, 2+,n=2,0,8	0 0%	1 100%
Follow-up (week 8), Ketones, n=4,7,8	0 0%	0 0%	1 33.3%
Follow up (week 8), Occult blood, n=4,7,8	1 33.3%	0 0%	1 33.3%
Follow-up(week 8),Occult blood,Trace-lysed,n=4,7,8	0 0%	0 0%	2 66.7%

20. Primary Outcome

Title	Urine pH Analysis by Dipstick Method for Part B
Description	Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 8 weeks in Part B. Only those participants available at the specified time points were analyzed represented by n=x in the category titles. Period 1 = Cohort 1 in Part B, Period 2 = Cohort 2 in Part B.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description
Safety Population for Part B

Arm/Group Title	Part B-Matching Placebo	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	4	7	8
pH, Period 1, Day -1, n=2, 7, 0	6.25 (0.354)	6.71 (0.906)
pH, Period 1, Day 4, n= 2, 7, 0	6.25 (0.354)	5.79 (0.393)
pH, Period 1, Day 6, n=2, 7, 0	6.25 (0.354)	6.43 (0.535)
pH, Period 1, Day 10, n=2, 7, 0	6.25 (0.354)	6.14 (0.244)
pH, Period 1, Day 14, n=2, 7, 0	6.75 (0.354)	7.00 (0.957)
pH, Period 2, Day -1, n=2, 0, 8	6.50 (0.707)	6.81 (0.594)
pH, Period 2, Day 4, n=2, 0, 8	5.50 (0.707)	6.25 (0.378)
pH, Period 2, Day 6, n=2, 0, 8	6.50 (0.000)	6.69 (0.458)
pH, Period 2, Day 10, n=2, 0, 8	6.00 (0.000)	6.38 (0.354)
pH, Period 2, Day 14, n=2, 0, 8	6.00 (0.000)	6.38 (0.582)
pH, Follow-up (week 8), n=4, 7, 8	6.63 (0.750)	6.29 (0.488)	6.88 (0.744)

21. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]) Following Single Dose Administration of GSK3036656 for Part A
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 Ethylenediaminetetraacetic acid (EDTA) tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. PK population comprised of participants in the Safety population who administered at least one dose of active treatment and had at least one evaluable PK sample.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hour*nanograms/milliliter]	771.0468 (26.0)	3252.9152 (24.1)	5686.4151 (11.4)	782.7766 (18.1)

22. Primary Outcome

Title	AUC From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3036656 Following Single Dose Administration for Part A
Description	Cmax will be derived from the PK samples collected at the indicated time points Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hour*nanograms/milliliter]	1404.5416 (29.9)	3796.1488 (19.8)	6557.7764 (13.8)	1450.7468 (9.4)

23. Primary Outcome

Title	Maximum Observed Plasma Drug Concentration (Cmax) of GSK3036656 Following Single Dose Administration for Part A
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter]	49.06 (30.5)	177.61 (23.1)	207.38 (18.5)	47.37 (23.5)

24. Primary Outcome

Title	Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3036656 Following Single Dose Administration for Part A
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Median (Full Range) [hours]	1.250	1.000	0.875	2.000

25. Primary Outcome

Title	Apparent Terminal Half-life (t1/2) of GSK3036656 Following Single Dose Administration for Part A
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Median (Full Range) [hours]	38.3230	28.4128	47.9680	32.4248

26. Primary Outcome

Title	AUC[0-t] Following Repeated Dose Administration of GSK3036656 for Part B
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1. The actual date and time of each blood sample collection was recorded. Results presented are for Day 1.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Geometric Mean (Geometric Coefficient of Variation) [hour*nanograms/milliliter]	485.5625 (12.3)	1891.0416 (9.9)

27. Primary Outcome

Title	AUC From Time Zero During a Dosing Interval of Duration Tau (AUC[0-tau]) of GSK3036656 Following Repeated Dose Administration for Part B
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14The actual date and time of each blood sample collection was recorded. Results presented are for Day 14.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Geometric Mean (Geometric Coefficient of Variation) [hour*nanograms/milliliter]	1392.2221 (12.5)	4461.2565 (23.7)

28. Primary Outcome

Title	Cmax of GSK3036656 Following Repeated Dose Administration for Part B
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. The actual date and time of each blood sample collection was recorded.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Day 1	48.40 (33.6)	178.79 (32.8)
Day 14	97.04 (19.8)	309.55 (20.2)

29. Primary Outcome

Title	Tmax of GSK3036656 Following Repeat Dose Administration for Part B
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. The actual date and time of each blood sample collection was recorded.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Day 1	1.0000	0.7500
Day 14	0.7500	0.7500

30. Primary Outcome

Title	t1/2 of GSK3036656 Following Repeated Dose Administration for Part B
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14. The actual date and time of each blood sample collection was recorded. Results presented are for Day 14.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14.

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Median (Full Range) [hours]	40.1802	34.5109

31. Secondary Outcome

Title	AUC (0-t) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hours*nanograms/milliliter]	771.0468 (26.0)	3252.9152 (24.1)	5686.4151 (11.4)	782.7766 (18.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 25 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 90% 0.87 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mixed Effect Model has been used to assess Food Effect for the log transformed parameter AUC(0-t). Treatment in the fed/fasted state is fitted as Fixed Effect. Participant is fitted as Random Effect. Variance Components covariance structure is used.

32. Secondary Outcome

Title	AUC (0-infinity) of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hours*nanograms/milliliter]	1404.5416 (29.9)	3796.1488 (19.8)	6557.7764 (13.8)	1450.7468 (9.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 25 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 90% 0.71 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mixed Effect Model has been used to assess Food Effect for the log transformed parameter AUC(0-inf). Treatment in the fed/fasted state is fitted as Fixed Effect. Participant is fitted as Random Effect. Variance Components covariance structure is use

33. Secondary Outcome

Title	Cmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter]	49.06 (30.5)	177.61 (23.1)	207.38 (18.5)	35.54 (23.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 25 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 90% 0.76 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mixed Effect Model has been used to assess Food Effect for the log transformed parameter Cmax. Treatment in the fed/fasted state is fitted as Fixed Effect. Participant is fitted as Random Effect. Variance Components covariance structure is used.

34. Secondary Outcome

Title	t1/2 of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Median (Full Range) [hours]	38.3230	28.4128	47.9680	32.4248

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 25 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 90% 0.64 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Fixed Effect Model has been used to assess Food Effect for the log transformed parameter t1/2 Treatment in the fed/fasted state is fitted as Fixed Effect.

35. Secondary Outcome

Title	Tmax of GSK3036656 Following Single Dose Administration in Fed Condition in Part A
Description	Blood samples for plasma PK analysis of GSK3036656 was collected into K3 EDTA tubes at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. The actual date and time of each blood sample collection was recorded. For the food effect assessment, the selected dose was given with a high fat meal.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Median (Full Range) [hours]	1.250	1.000	0.875	2.000

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 25 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 90% -0.50 to 2.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hodges-Lehmann estimation is used to calculate the 90% confidence interval.

36. Secondary Outcome

Title	Observed Accumulation Ratio Based on AUC (AUC [Ro]) of GSK3036656 in Part B
Description	AUC Ro was calculated as Day 14 AUC(0-tau)/Day 1 AUC(0-t), where t and tau= 24 hours.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Geometric Mean (Geometric Coefficient of Variation) [Ratio of AUC]	2.8672 (9.1)	2.3592 (21.6)

37. Secondary Outcome

Title	Observed Accumulation Ratio Based on Cmax (RCmax) of GSK3036656 in Part B
Description	Rcmax was calculated as Day 14 Cmax/Day 1 Cmax. Statistics has been presented on geometric least square means.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Geometric Mean (Geometric Coefficient of Variation) [Ratio of Cmax]	2.0052 (24.3)	1.7313 (26.7)

38. Secondary Outcome

Title	Steady State Ratio (Rss) of GSK3036656 in Part B
Description	Rss was calculated as Day 14 AUC (0-tau)/Day 1 AUC (0-inf). It was not possible to calculate AUC(0-inf) on Day 1 for the repeat dosing period, therefore it was not possible to calculate the (Rss).Na indicates data was not available.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Geometric Mean (Geometric Coefficient of Variation) [Ratio of AUC]	NA (NA)	NA (NA)

39. Secondary Outcome

Title	Trough Plasma Concentrations at the End of the Dosing Interval (Ctau) of GSK3036656 Following Repeat Dose Administrations in Part B
Description	Blood samples for the analysis of Ctau were collected at Day 1 (24 hours), Day 12 (Pre-dose ), Day 13 (Pre-dose ), Day 14 (Pre-dose), Day 14 (24 hours). Ctau samples collected were used to assess attainment of steady state. Statistics has been presented on geometric least square means.
Time Frame	Day 1 (24 hours), Day 12 (Pre-dose ), Day 13 (Pre-dose ), Day 14 (Pre-dose), Day 14 (24 hours)

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Day 1, 24 hours	14.32 (10.8)	57.69 (10.5)
Day 12, Pre-dose	38.31 (20.8)	139.14 (21.6)
Day 13, Pre-dose	41.78 (14.5)	131.77 (28.8)
Day 14, Pre-dose	43.66 (15.1)	139.54 (32.5)
Day 14, 24 hours	44.34 (14.8)	139.25 (28.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo
	Comments	Repeat GSK3036656 5mg Day 1-14
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 90% 1.09 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mixed Effect Model has been used to assess Steady State. Day is fitted as a Fixed Effect. Participant is fitted as Random Effect Variance Components covariance structure is used.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A-GSK3036656 5 mg
	Comments	Repeat GSK3036656 15mg Day 1-14
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 90% 1.07 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mixed Effect Model has been used to assess Steady State. Day is fitted as a Fixed Effect. Participant is fitted as Random Effect Variance Components covariance structure is used.

40. Secondary Outcome

Title	AUC (0-infinity) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A
Description	Blood samples for the analysis of AUC (0-infinity) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. AUC(0-infinity) following single doses was used for assessment of dose proportionality.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hours*nanograms/milliliter]	1404.5416 (29.9)	3796.1488 (19.8)	6557.7764 (13.8)	1450.7468 (9.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 90% 0.82 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	A slope of 1 indicates the pharmacokinetics are dose proportional. A slope greater than 1 indicates the increase in PK is greater than proportional to dose.

Other Statistical Analysis		Power Model has been used to assess Dose Proportionality. Log-e(dose) is fitted as Fixed Effect and Participant is fitted as Random Effect. An Unstructured covariance structure is used.

41. Secondary Outcome

Title	AUC (0-t) as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A
Description	Blood samples for the analysis of AUC (0-t) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. AUC(0-t) following single doses was used for assessment of dose proportionality.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hours*nanograms/milliliter]	771.0468 (26.0)	3252.9152 (24.1)	5686.4151 (11.4)	782.7766 (18.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 90% 1.24 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Power Model has been used to assess Dose Proportionality. Log-e(dose) is fitted as Fixed Effect and Participant is fitted as Random Effect. An Unstructured covariance structure is used.

42. Secondary Outcome

Title	Cmax as a Measure of Dose Proportionality of GSK3036656 Following Single Dose Administrations for Part A
Description	Blood samples for the analysis of Cmax were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period. Cmax following single doses was used for assessment of dose proportionality.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1 in each period

Outcome Measure Data

Analysis Population Description
PK Population for Part A

Arm/Group Title	Part A-GSK3036656 5 mg	Part A-GSK3036656 15 mg	Part A-GSK3036656 25 mg	Part A-GSK3036656 5 mg (Fed)
Arm/Group Description	Participants received single dosing of GSK3036656 5 mg capsules orally.	Participants received single dosing of GSK3036656 15 mg capsules orally.	Participants received single dosing of GSK3036656 25 mg capsules orally.	Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.
Measure Participants	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hours*nanograms/milliliter]	49.06 (30.5)	177.61 (23.1)	207.38 (18.5)	47.37 (23.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 90% 0.81 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Power Model has been used to assess Dose Proportionality. Log-e(dose) is fitted as Fixed Effect and Participant is fitted as Random Effect. An Unstructured covariance structure is used.

43. Secondary Outcome

Title	AUC (0-tau) as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B
Description	Blood samples for the assessment of AUC (0-tau) were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. AUC (0-tau) following repeat doses was used for assessment of dose proportionality.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Geometric Mean (Geometric Coefficient of Variation) [hours*nanograms/milliliter]	1392.2221 (12.5)	4461.2565 (23.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 90% 1.15 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 1.Power Model has been used to assess Dose Proportionality. Log-e(dose) is fitted as Fixed Effect.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 90% 0.90 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 14. Power Model has been used to assess Dose Proportionality. Log-e(dose) is fitted as Fixed Effect.

44. Secondary Outcome

Title	Cmax as a Measure of Dose Proportionality of GSK3036656 Following Repeat Dose Administrations for Part B
Description	Blood samples for the assessment of Cmax were collected at Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13. Cmax following repeat doses was used for assessment of dose proportionality.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 1; at pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hour post-dose on Day 14; and at pre-dose on Days 12 and 13

Outcome Measure Data

Analysis Population Description
PK Population for Part B

Arm/Group Title	Part B-Repeat GSK3036656 5 mg	Part B-Repeat GSK3036656 15 mg
Arm/Group Description	Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.	Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
Measure Participants	7	8
Day 1	48.40 (33.6)	178.79 (32.8)
Day 14	97.04 (19.8)	309.55 (20.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 90% 0.92 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 1. Power Model has been used to assess Dose Proportionality. Log-e(dose) is fitted as Fixed Effect.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A-Matching Placebo, Part A-GSK3036656 5 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 90% 0.89 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Day 14. Power Model has been used to assess Dose Proportionality. Log-e(dose) is fitted as Fixed Effect.

Adverse Events

	Part A-Matching Placebo		Part A-GSK3036656 5 mg		Part A-GSK3036656 15 mg		Part A-GSK3036656 25 mg		Part A-GSK3036656 5 mg (Fed)		Part B-Matching Placebo		Part B-GSK3036656 5 mg		Part B-GSK3036656 15 mg
Time Frame	nSAEs and SAEs were collected from Day -1 until 12 weeks in Part A and until 8 weeks in Part B.
Adverse Event Reporting Description	Safety Population was used to assess nSAEs and SAEs.

Arm/Group Title	Part A-Matching Placebo		Part A-GSK3036656 5 mg		Part A-GSK3036656 15 mg		Part A-GSK3036656 25 mg		Part A-GSK3036656 5 mg (Fed)		Part B-Matching Placebo		Part B-GSK3036656 5 mg		Part B-GSK3036656 15 mg
Arm/Group Description	Participants received single dosing of matching placebo to GSK3036656 5 mg capsules orally.		Participants received single dosing of GSK3036656 5 mg capsules orally.		Participants received single dosing of GSK3036656 15 mg capsules orally.		Participants received single dosing of GSK3036656 25 mg capsules orally.		Participants received single dosing of GSK3036656 5 mg capsules in the fed state orally.		Participants received matching placebo to active GSK3036656 5 mg / 15mg capsules orally once daily for 14 days.		Participants received repeat dosing of GSK3036656 5 mg capsules orally once daily for 14 days.		Participants received repeat dosing of GSK3036656 15 mg capsules orally once daily for 14 days.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/4 (0%)		0/7 (0%)		0/8 (0%)
Serious Adverse Events
	Part A-Matching Placebo		Part A-GSK3036656 5 mg		Part A-GSK3036656 15 mg		Part A-GSK3036656 25 mg		Part A-GSK3036656 5 mg (Fed)		Part B-Matching Placebo		Part B-GSK3036656 5 mg		Part B-GSK3036656 15 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/4 (0%)		0/7 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Part A-Matching Placebo		Part A-GSK3036656 5 mg		Part A-GSK3036656 15 mg		Part A-GSK3036656 25 mg		Part A-GSK3036656 5 mg (Fed)		Part B-Matching Placebo		Part B-GSK3036656 5 mg		Part B-GSK3036656 15 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		1/6 (16.7%)		1/6 (16.7%)		3/6 (50%)		1/5 (20%)		0/4 (0%)		2/7 (28.6%)		1/8 (12.5%)
Gastrointestinal disorders
Abdominal pain	0/9 (0%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		0/5 (0%)		0/4 (0%)		0/7 (0%)		0/8 (0%)
Dyspepsia	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/4 (0%)		0/7 (0%)		0/8 (0%)
Diarrhoea	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/4 (0%)		0/7 (0%)		1/8 (12.5%)
General disorders
Medical device site dermatitis	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/5 (0%)		0/4 (0%)		0/7 (0%)		0/8 (0%)
Medical device site reaction	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/4 (0%)		1/7 (14.3%)		0/8 (0%)
Infections and infestations
Infectious mononucleosis	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/4 (0%)		1/7 (14.3%)		0/8 (0%)
Investigations
Liver function test increased	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/4 (0%)		1/7 (14.3%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/5 (0%)		0/4 (0%)		0/7 (0%)		0/8 (0%)
Nervous system disorders
Headache	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/5 (0%)		0/4 (0%)		2/7 (28.6%)		0/8 (0%)
Dizziness	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/4 (0%)		1/7 (14.3%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/5 (20%)		0/4 (0%)		0/7 (0%)		0/8 (0%)
Epistaxis	0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/5 (0%)		0/4 (0%)		0/7 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email	GSKClinicalSupportHD@gsk.com

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT03075410

Other Study ID Numbers:

201040
2015-003654-41

First Posted:

Mar 9, 2017

Last Update Posted:

Apr 19, 2019

Last Verified:

Jan 1, 2019