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

• ClinicalTrials.gov Identifier: NCT03075410
• Recruitment Status: Completed
• First Posted: March 9, 2017
• Results First Posted: April 19, 2019
• Last Update Posted: April 19, 2019
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Tuberculosis
• Interventions: Drug: GSK3036656; Drug: Placebo
• Enrollment: 30

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 Details	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-Washout 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 2 (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
Reason Not Completed
Personal reasons	1	0	1	0	0	0	0	0	0
Period Title: Part A-Washout Period 2 (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 3 (14 Days)
Started	2 [1]	1	2 [1]	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
Reason Not Completed
Reaction to ECG tabs causing a rash	1	0	0	0	0	0	0	0	0
[1] Participants who withdrew in Period 2 were replaced (2 new participants entered Part A period 3).
Period Title: Part A-Washout Period 3 (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 4 (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 B (up to 28 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 Number of Baseline Participants		3	1	3	1	2	1	4	7	8	30
Baseline Analysis Population Description		9 participants were randomized at the beginning of Part A. During Part A, 2 of the 3 participants who withdrew were replaced, hence 11 randomized.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	3 participants	1 participants	3 participants	1 participants	2 participants	1 participants	4 participants	7 participants	8 participants	30 participants
		33.7 (5.03)	25 [1] (NA)	26.3 (2.52)	28.0 [1] (NA)	34.0 (1.41)	50.0 [1] (NA)	30.3 (9.43)	31.9 (6.26)	35.1 (7.88)	32.5 (7.39)
		[1] Standard deviation was not calculated as a single participant was analyzed.
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	1 participants	3 participants	1 participants	2 participants	1 participants	4 participants	7 participants	8 participants	30 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 100.0%	0 0.0%	0 0.0%	0 0.0%	1 3.3%
	Male	3 100.0%	1 100.0%	3 100.0%	1 100.0%	2 100.0%	0 0.0%	4 100.0%	7 100.0%	8 100.0%	29 96.7%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	3 participants	1 participants	3 participants	1 participants	2 participants	1 participants	4 participants	7 participants	8 participants	30 participants
American Indian/Alaskan Native		1 33.3%	0 0.0%	0 0.0%	0 0.0%	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 0.0%	0 0.0%	1 50.0%	0 0.0%	1 25.0%	0 0.0%	0 0.0%	2 6.7%
Black/ African American		1 33.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 14.3%	0 0.0%	2 6.7%
White-White/Caucasian/European Heritage		1 33.3%	1 100.0%	3 100.0%	1 100.0%	1 50.0%	1 100.0%	2 50.0%	5 71.4%	8 100.0%	23 76.7%
Unknown		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 25.0%	1 14.3%	0 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.
Overall Number of Participants Analyzed	9	6	6	6	5
Measure Type: Count of Participants; Unit of Measure: Participants
nSAE	1 11.1%	1 16.7%	1 16.7%	3 50.0%	1 20.0%
SAE	0 0.0%	0 0.0%	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.
Overall Number of Participants Analyzed	4	7	8
Measure Type: Count of Participants; Unit of Measure: Participants
nSAE	0 0.0%	2 28.6%	1 12.5%
SAE	0 0.0%	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.
Overall Number of Participants Analyzed	9	6	6	6	5
Measure Type: Count of Participants; Unit of Measure: Participants
A-NCS	2 22.2%	1 16.7%	0 0.0%	0 0.0%	0 0.0%
A-CS	0 0.0%	0 0.0%	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.
Overall Number of Participants Analyzed	4	7	8
Measure Type: Count of Participants; Unit of Measure: Participants
A-NCS	1 25.0%	3 42.9%	3 37.5%
A-CS	0 0.0%	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.
Overall Number of Participants Analyzed	9	6	6	6	5
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	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.
Overall Number of Participants Analyzed	4	7	8
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	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.
Overall Number of Participants Analyzed	9	6	6	6	5
Measure Type: Count of Participants; Unit of Measure: Participants
SBP	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
DBP	0 0.0%	0 0.0%	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.
Overall Number of Participants Analyzed	4	7	8
Measure Type: Count of Participants; Unit of Measure: Participants
SBP	0 0.0%	0 0.0%	0 0.0%
DBP	0 0.0%	0 0.0%	1 12.5%

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.
Overall Number of Participants Analyzed	9	6	6	6	5
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	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.
Overall Number of Participants Analyzed	4	7	8
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	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.
Overall Number of Participants Analyzed	9	6	6	6	5
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	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.
Overall Number of Participants Analyzed	4	7	8
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	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.
Overall Number of Participants Analyzed	9	6	6	6	5
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 20.0%

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.
Overall Number of Participants Analyzed	4	7	8
Measure Type: Count of Participants; Unit of Measure: Participants
ALT	0 0.0%	1 14.3%	0 0.0%
AST	0 0.0%	1 14.3%	0 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.
Overall Number of Participants Analyzed	9	6	6	6	5
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	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.
Overall Number of Participants Analyzed	4	7	8
Measure Type: Count of Participants; Unit of Measure: Participants
Leukocytes	0 0.0%	1 14.3%	0 0.0%
Neutrophils	0 0.0%	1 14.3%	1 12.5%

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.
Overall Number of Participants Analyzed	9	6	6	6	5
Measure Type: Count of Participants; Unit of Measure: Participants
Day -1, Ketone, Trace	1 11.1%	0 0.0%	1 16.7%	0 0.0%	0 0.0%
Day -1, Occult blood, 1+	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 20.0%
Day -1, Occult blood, 2+	0 0.0%	0 0.0%	1 16.7%	0 0.0%	0 0.0%
Day -1, Occult blood, trace-intact	1 11.1%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Day -1, Occult blood, trace-lysed	1 11.1%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Day -1, Protein, Trace	1 11.1%	0 0.0%	2 33.3%	0 0.0%	1 20.0%
24 hours, Ketones, 2+	1 11.1%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
24 hours, Occult blood, 2+	0 0.0%	0 0.0%	1 16.7%	0 0.0%	0 0.0%
24 hours, Occult blood, trace-intact	1 11.1%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
24 hours, Occult blood, trace-lysed	1 11.1%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
72 hours, Ketone, Trace	0 0.0%	0 0.0%	1 16.7%	0 0.0%	0 0.0%
72 hours, Occult blood, 1+	1 11.1%	0 0.0%	1 16.7%	0 0.0%	0 0.0%
72 hours, Occult blood, trace-intact	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 20.0%
72 hours, Occult blood, trace-lysed	0 0.0%	0 0.0%	0 0.0%	1 16.7%	0 0.0%
72 hours, Protein, Trace	2 22.2%	0 0.0%	0 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.
Overall Number of Participants Analyzed	9	6	6	6	5
Mean (Standard Deviation); Unit of Measure: pH
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.
Overall Number of Participants Analyzed		4	7	8
Measure Type: Count of Participants; Unit of Measure: Participants
Day -1, Ketones, Trace,n=2,7,0	Number Analyzed	2 participants	7 participants	0 participants
		0 0.0%	1 14.3%
Day -1, Occult blood,Trace-intact,n=2,7,0	Number Analyzed	2 participants	7 participants	0 participants
		1 50.0%	0 0.0%
Day 14, Ketones, Trace,n=2,7,0	Number Analyzed	2 participants	7 participants	0 participants
		0 0.0%	1 14.3%
Day 14, protein, 1+,n=2,7,0	Number Analyzed	2 participants	7 participants	0 participants
		0 0.0%	1 14.3%
Day -1,Occult blood,Trace-intact,n=2,0,8	Number Analyzed	2 participants	0 participants	8 participants
		1 50.0%		2 25.0%
Day 6,Occult blood,Trace-intact,n=2,0,8	Number Analyzed	2 participants	0 participants	8 participants
		0 0.0%		1 12.5%
Day 6,Occult blood,Trace-lysed,n=2,0,8	Number Analyzed	2 participants	0 participants	8 participants
		0 0.0%		2 25.0%
Day 10, Ketones, Trace,n=2,0,8	Number Analyzed	2 participants	0 participants	8 participants
		0 0.0%		1 12.5%
Day 14, Protein, 2+,n=2,0,8	Number Analyzed	2 participants	0 participants	8 participants
		0 0.0%		1 12.5%
Follow-up (week 8), Ketones, n=4,7,8	Number Analyzed	4 participants	7 participants	8 participants
		0 0.0%	0 0.0%	1 12.5%
Follow up (week 8), Occult blood, n=4,7,8	Number Analyzed	4 participants	7 participants	8 participants
		1 25.0%	0 0.0%	1 12.5%
Follow-up(week 8),Occult blood,Trace-lysed,n=4,7,8	Number Analyzed	4 participants	7 participants	8 participants
		0 0.0%	0 0.0%	2 25.0%

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.
Overall Number of Participants Analyzed		4	7	8
Mean (Standard Deviation); Unit of Measure: pH
pH, Period 1, Day -1, n=2, 7, 0	Number Analyzed	2 participants	7 participants	0 participants
		6.25 (0.354)	6.71 (0.906)
pH, Period 1, Day 4, n= 2, 7, 0	Number Analyzed	2 participants	7 participants	0 participants
		6.25 (0.354)	5.79 (0.393)
pH, Period 1, Day 6, n=2, 7, 0	Number Analyzed	2 participants	7 participants	0 participants
		6.25 (0.354)	6.43 (0.535)
pH, Period 1, Day 10, n=2, 7, 0	Number Analyzed	2 participants	7 participants	0 participants
		6.25 (0.354)	6.14 (0.244)
pH, Period 1, Day 14, n=2, 7, 0	Number Analyzed	2 participants	7 participants	0 participants
		6.75 (0.354)	7.00 (0.957)
pH, Period 2, Day -1, n=2, 0, 8	Number Analyzed	2 participants	0 participants	8 participants
		6.50 (0.707)		6.81 (0.594)
pH, Period 2, Day 4, n=2, 0, 8	Number Analyzed	2 participants	0 participants	8 participants
		5.50 (0.707)		6.25 (0.378)
pH, Period 2, Day 6, n=2, 0, 8	Number Analyzed	2 participants	0 participants	8 participants
		6.50 (0.000)		6.69 (0.458)
pH, Period 2, Day 10, n=2, 0, 8	Number Analyzed	2 participants	0 participants	8 participants
		6.00 (0.000)		6.38 (0.354)
pH, Period 2, Day 14, n=2, 0, 8	Number Analyzed	2 participants	0 participants	8 participants
		6.00 (0.000)		6.38 (0.582)
pH, Follow-up (week 8), n=4, 7, 8	Number Analyzed	4 participants	7 participants	8 participants
		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.
Overall Number of Participants Analyzed	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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.
Overall Number of Participants Analyzed	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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.
Overall Number of Participants Analyzed	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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.
Overall Number of Participants Analyzed	6	6	6	5
Median (Full Range); Unit of Measure: hours
	1.250; (0.50 to 1.50)	1.000; (0.50 to 2.00)	0.875; (0.75 to 2.00)	2.000; (1.00 to 4.00)

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.
Overall Number of Participants Analyzed	6	6	6	5
Median (Full Range); Unit of Measure: hours
	38.3230; (25.632 to 70.970)	28.4128; (24.462 to 32.497)	47.9680; (35.996 to 67.360)	32.4248; (30.449 to 46.455)

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.
Overall Number of Participants Analyzed	7	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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.
Overall Number of Participants Analyzed	7	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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.
Overall Number of Participants Analyzed	7	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanograms/milliliter
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.
Overall Number of Participants Analyzed	7	8
Median (Full Range); Unit of Measure: hours
Day 1	1.0000; (0.500 to 3.000)	0.7500; (0.500 to 1.500)
Day 14	0.7500; (0.500 to 1.500)	0.7500; (0.500 to 1.500)

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.
Overall Number of Participants Analyzed	7	8
Median (Full Range); Unit of Measure: hours
	40.1802; (30.843 to 66.636)	34.5109; (24.758 to 54.625)

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.
Overall Number of Participants Analyzed	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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-GSK3036656 5 mg, Part A-GSK3036656 5 mg (Fed)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 90%; 0.87 to 1.34
	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.
Overall Number of Participants Analyzed	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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-GSK3036656 5 mg, Part A-GSK3036656 5 mg (Fed)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 90%; 0.71 to 1.26
	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.
Overall Number of Participants Analyzed	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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-GSK3036656 5 mg, Part A-GSK3036656 5 mg (Fed)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 90%; 0.76 to 1.23
	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.
Overall Number of Participants Analyzed	6	6	6	5
Median (Full Range); Unit of Measure: hours
	38.3230; (25.632 to 70.970)	28.4128; (24.462 to 32.497)	47.9680; (35.996 to 67.360)	32.4248; (30.449 to 46.455)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-GSK3036656 5 mg, Part A-GSK3036656 5 mg (Fed)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 90%; 0.64 to 1.23
	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.
Overall Number of Participants Analyzed	6	6	6	5
Median (Full Range); Unit of Measure: hours
	1.250; (0.50 to 1.50)	1.000; (0.50 to 2.00)	0.875; (0.75 to 2.00)	2.000; (1.00 to 4.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A-GSK3036656 5 mg, Part A-GSK3036656 5 mg (Fed)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 90%; -0.50 to 2.50
	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.
Overall Number of Participants Analyzed	7	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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.
Overall Number of Participants Analyzed	7	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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.
Overall Number of Participants Analyzed	7	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of AUC
	NA [1]; (NA%)	NA [1]; (NA%)

[1]

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 steady state ratio (Rss).

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.
Overall Number of Participants Analyzed	7	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanograms/milliliter
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 B-Repeat GSK3036656 5 mg
	Comments	Repeat GSK3036656 5mg Day 1-14
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 90%; 1.09 to 1.10
	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 B-Repeat GSK3036656 15 mg
	Comments	Repeat GSK3036656 15mg Day 1-14
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 90%; 1.07 to 1.08
	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.
Overall Number of Participants Analyzed	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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-GSK3036656 5 mg, Part A-GSK3036656 15 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 90%; 0.82 to 1.10
	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.
Overall Number of Participants Analyzed	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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-GSK3036656 5 mg, Part A-GSK3036656 15 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 90%; 1.24 to 1.39
	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.
Overall Number of Participants Analyzed	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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-GSK3036656 5 mg, Part A-GSK3036656 15 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 90%; 0.81 to 1.11
	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.
Overall Number of Participants Analyzed	7	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours*nanograms/milliliter
	1392.2221; (12.5%)	4461.2565; (23.7%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B-Repeat GSK3036656 5 mg, Part B-Repeat GSK3036656 15 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 90%; 1.15 to 1.33
	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 B-Repeat GSK3036656 5 mg, Part B-Repeat GSK3036656 15 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 90%; 0.90 to 1.22
	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.
Overall Number of Participants Analyzed	7	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanograms/milliliter
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 B-Repeat GSK3036656 5 mg, Part B-Repeat GSK3036656 15 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 90%; 0.92 to 1.46
	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 B-Repeat GSK3036656 5 mg, Part B-Repeat GSK3036656 15 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 90%; 0.89 to 1.22
	Estimation Comments	Day 14. Power Model has been used to assess Dose Proportionality. Log-e(dose) is fitted as Fixed Effect.

Adverse Events

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
	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 (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/4 (0.00%)	0/7 (0.00%)	0/8 (0.00%)
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 (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/4 (0.00%)	0/7 (0.00%)	0/8 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	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 (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/9 (11.11%)	1/6 (16.67%)	1/6 (16.67%)	3/6 (50.00%)	1/5 (20.00%)	0/4 (0.00%)	2/7 (28.57%)	1/8 (12.50%)
Gastrointestinal disorders
Abdominal pain † 1	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	2/6 (33.33%)	0/5 (0.00%)	0/4 (0.00%)	0/7 (0.00%)	0/8 (0.00%)
Dyspepsia † 1	1/9 (11.11%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/4 (0.00%)	0/7 (0.00%)	0/8 (0.00%)
Diarrhoea † 1	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/4 (0.00%)	0/7 (0.00%)	1/8 (12.50%)
General disorders
Medical device site dermatitis † 1	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/5 (0.00%)	0/4 (0.00%)	0/7 (0.00%)	0/8 (0.00%)
Medical device site reaction † 1	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/4 (0.00%)	1/7 (14.29%)	0/8 (0.00%)
Infections and infestations
Infectious mononucleosis † 1	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/4 (0.00%)	1/7 (14.29%)	0/8 (0.00%)
Investigations
Liver function test increased † 1	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/4 (0.00%)	1/7 (14.29%)	0/8 (0.00%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain † 1	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/5 (0.00%)	0/4 (0.00%)	0/7 (0.00%)	0/8 (0.00%)
Nervous system disorders
Headache † 1	0/9 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/6 (16.67%)	0/5 (0.00%)	0/4 (0.00%)	2/7 (28.57%)	0/8 (0.00%)
Dizziness † 1	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/4 (0.00%)	1/7 (14.29%)	0/8 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/9 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/5 (20.00%)	0/4 (0.00%)	0/7 (0.00%)	0/8 (0.00%)
Epistaxis † 1	0/9 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/4 (0.00%)	0/7 (0.00%)	0/8 (0.00%)
1 Term from vocabulary, MedDRA 20.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tenero D, Derimanov G, Carlton A, Tonkyn J, Davies M, Cozens S, Gresham S, Gaudion A, Puri A, Muliaditan M, Rullas-Trincado J, Mendoza-Losana A, Skingsley A, Barros-Aguirre D. First-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis Treatment. Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00240-19. doi: 10.1128/AAC.00240-19. Print 2019 Aug.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03075410
• Other Study ID Numbers: 201040; 2015-003654-41 ( EudraCT Number )
• First Submitted: March 6, 2017
• First Posted: March 9, 2017
• Results First Submitted: August 3, 2018
• Results First Posted: April 19, 2019
• Last Update Posted: April 19, 2019