An Early Bactericidal Activity, Safety and Tolerability of GSK3036656 in Subjects With Drug-sensitive Pulmonary Tuberculosis

• ClinicalTrials.gov Identifier: NCT03557281
• Recruitment Status: Completed
• First Posted: June 15, 2018
• Results First Posted: October 26, 2023
• Last Update Posted: October 26, 2023
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Tuberculosis
• Interventions: Drug: GSK3036656; Drug: Rifafour e-275
• Enrollment: 76

Participant Flow

Recruitment Details	This was an open-label trial to investigate the early bactericidal activity, safety and tolerability of GSK3036656 in participants with drug-sensitive pulmonary tuberculosis. Participants received Rifafour e-275 as a standard-of-care or GSK3036656. Rifafour e-275 is a registered trademark of Sanofi-Aventis company.
Pre-assignment Details	A total of 76 participants were enrolled (Enrolled Population consisted of all participants who passed screening and entered the study) in this study.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Period Title: Overall Study
Started	18	9	17	16	16
Safety Population Consisted of All Randomized Participants Who Received at Least 1 Dose of Treatment	18	9	17	16	15
Completed	18	8	15	15	13
Not Completed	0	1	2	1	3
Reason Not Completed
Investigator discretion	0	0	1	0	0
Withdrawal by Subject	0	1	1	1	2
Randomized, but did not receive treatment	0	0	0	0	1

Baseline Characteristics

Arm/Group Title		Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg	Total
Arm/Group Description		All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.	Total of all reporting groups
Overall Number of Baseline Participants		18	9	17	16	15	75
Baseline Analysis Population Description		Safety Population consisted of all randomized participants who received at least one dose of study treatment.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	18 participants	9 participants	17 participants	16 participants	15 participants	75 participants
		37.0 (10.20)	37.8 (8.38)	38.1 (10.33)	39.8 (12.33)	38.5 (9.82)	38.2 (10.22)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants	9 participants	17 participants	16 participants	15 participants	75 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Male	18 100.0%	9 100.0%	17 100.0%	16 100.0%	15 100.0%	75 100.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants	9 participants	17 participants	16 participants	15 participants	75 participants
	Black or African American	18 100.0%	9 100.0%	17 100.0%	16 100.0%	15 100.0%	75 100.0%

Outcome Measures

1. Primary Outcome

Title	Change in log10 Colony Forming Units (CFU) Per (/) Milliliter (mL) of Direct Respiratory Sputum Samples From Baseline to Day 14
Description	The Early Bactericidal Activity was determined by change in log10CFU/mL of sputum over the period Baseline to Day 14. Log(CFU) was calculated as: Log(CFU/mL)=log10(mean[Total count 1:Total Count 2]*2*5*10^Dilution); where total counts 1 and 2 were bacterial counts from plates 1 and 2 respectively; *2 represents the 1:1 dilution of the original specimen and *5 represents the 0.2 mL (200 microliter) inoculation of the specimen; Dilution is the dilution factor for that plate. Baseline (Day 0) was defined as the mean of Day -2 and Day -1; if data was available at only one of these timepoints then that value was used as Baseline.
Time Frame	Baseline and up to Day 14

Outcome Measure Data

Analysis Population Description

Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	9	17	16	15
Mean (Standard Error); Unit of Measure: Log10CFU/mL
	-0.199 (0.0130)	-0.017 (0.0182)	-0.092 (0.0136)	-0.092 (0.0142)	-0.138 (0.0147)

2. Secondary Outcome

Title	Change in log10 CFU/mL of Direct Respiratory Sputum Samples From Baseline to Day 2
Description	The Early Bactericidal Activity was determined by change in log10CFU per mL of sputum over the period Baseline to Day 2. Log(CFU) was calculated as: Log(CFU/mL)=log10(mean[Total count 1:Total Count 2]*2*5*10^Dilution); where total counts 1 and 2 were bacterial counts from plates 1 and 2 respectively; *2 represents the 1:1 dilution of the original specimen and *5 represents the 0.2 mL (200 microliter) inoculation of the specimen; Dilution is the dilution factor for that plate. Baseline (Day 0) was defined as the mean of Day -2 and Day -1; if data was available at only one of these timepoints then that value was used as Baseline.
Time Frame	Baseline and up to Day 2

Outcome Measure Data

Analysis Population Description

Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	17	9	17	16	15
Mean (Standard Error); Unit of Measure: log10CFU/mL
	-0.598 (0.0801)	0.250 (0.1077)	-0.153 (0.0801)	-0.055 (0.0832)	-0.040 (0.0855)

3. Secondary Outcome

Title	Change in log10 CFU Per mL of Direct Respiratory Sputum Samples From Day 2 to Day 14
Description	The Early Bactericidal Activity was determined by change in log10CFU per mL of sputum over the period Day 2 to Day 14. Log(CFU) was calculated as: Log(CFU/mL)=log10(mean[Total count 1:Total Count 2]*2*5*10^Dilution); where total counts 1 and 2 were bacterial counts from plates 1 and 2 respectively; *2 represents the 1:1 dilution of the original specimen and *5 represents the 0.2 mL (200 microliter) inoculation of the specimen; Dilution is the dilution factor for that plate.
Time Frame	Day 2 to Day 14

Outcome Measure Data

Analysis Population Description

Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	17	9	16	16	14
Mean (Standard Error); Unit of Measure: log10CFU/mL
	-0.162 (0.0169)	-0.037 (0.0233)	-0.080 (0.0173)	-0.086 (0.0181)	-0.129 (0.0192)

4. Secondary Outcome

Title	Change in log10 Time to Sputum Culture Positivity (TTP) From Baseline to Day 14
Description	The Early Bactericidal Activity was determined by change in TTP per mL sputum over the period Baseline to Day 14. The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) automated liquid culture system of time to positivity of Mycobacterium tuberculosis from an overnight sputum collection. Time to sputum-culture positivity was the time between sample inoculation and detection of mycobacterial growth in the mycobacterium growth indicator tube. Baseline (Day 0) was defined as the mean of Day -2 and Day -1; if data was available at only one of these timepoints then that value was used as Baseline.
Time Frame	Baseline and up to Day 14

Outcome Measure Data

Analysis Population Description

Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	9	17	16	15
Mean (Standard Error); Unit of Measure: log10hours
	0.025 (0.0010)	0.000 (0.0015)	0.015 (0.0011)	0.021 (0.0012)	0.022 (0.0013)

5. Secondary Outcome

Title	Change in log10 TTP From Baseline to Day 2
Description	The Early Bactericidal Activity was determined by change in TTP per mL sputum over the period Baseline to Day 2. The TTP was measured in the MGIT automated liquid culture system of time to positivity of Mycobacterium tuberculosis from an overnight sputum collection. Time to sputum-culture positivity was the time between sample inoculation and detection of mycobacterial growth in the mycobacterium growth indicator tube. Baseline (Day 0) was defined as the mean of Day -2 and Day -1; if data was available at only one of these timepoints then that value was used as Baseline.
Time Frame	Baseline and up to Day 2

Outcome Measure Data

Analysis Population Description

Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	9	17	16	15
Mean (Standard Error); Unit of Measure: log10hours
	0.105 (0.0068)	-0.003 (0.0096)	0.021 (0.0071)	0.032 (0.0072)	0.066 (0.0074)

6. Secondary Outcome

Title	Change in log10 TTP From Day 2 to Day 14
Description	The Early Bactericidal Activity was determined by change in TTP per mL sputum over the period Day 2 to Day 14. The TTP was measured in the MGIT automated liquid culture system of time to positivity of Mycobacterium tuberculosis from an overnight sputum collection. Time to sputum-culture positivity was the time between sample inoculation and detection of mycobacterial growth in the mycobacterium growth indicator tube.
Time Frame	Day 2 to Day 14

Outcome Measure Data

Analysis Population Description

Efficacy Population consisted of participants in the safety population who provided at least two evaluable overnight sputum samples. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	9	16	16	15
Mean (Standard Error); Unit of Measure: log10hours
	0.017 (0.0011)	0.001 (0.0016)	0.013 (0.0012)	0.017 (0.0012)	0.016 (0.0013)

7. Secondary Outcome

Title	Area Under the Plasma Drug Concentration Versus Time Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) Following Once Daily Dosing of GSK3036656
Description	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3036656.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description

PK Population consisted of participants in the safety population who received at least one dose of GSK3036656 and had at least one evaluable PK sample. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	8	14	14	13
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Hours*nanogram per milliliter
	281.8; (25.7%)	1495.6; (12.5%)	4493.8; (12.5%)	11505.6; (17.9%)

8. Secondary Outcome

Title	Area Under the Plasma Concentration Time Curve From Zero to 24 Hours (AUC[0-24]) Following Once Daily Dosing of GSK3036656
Description	Blood samples were collected at indicated time points for PK analysis of GSK3036656.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description

PK Population consisted of participants in the safety population who received at least one dose of GSK3036656 and had at least one evaluable PK sample. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	8	14	14	13
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Hours*nanogram per milliliter
	282.1; (25.8%)	1497.1; (12.4%)	4493.9; (12.5%)	11540.0; (17.8%)

9. Secondary Outcome

Title	Maximum Observed Plasma Drug Concentration (Cmax) Following Once Daily Dosing of GSK3036656
Description	Blood samples were collected at indicated time points for PK analysis of GSK3036656.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description

PK Population consisted of participants in the safety population who received at least one dose of GSK3036656 and had at least one evaluable PK sample. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	8	14	14	13
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Nanogram per milliliter
	16.93; (23.7%)	94.60; (24.7%)	291.41; (18.9%)	705.24; (20.2%)

10. Secondary Outcome

Title	Time to Reach Cmax (Tmax) Following Once Daily Dosing of GSK3036656
Description	Blood samples were collected at indicated time points for PK analysis of GSK3036656.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description

PK Population consisted of participants in the safety population who received at least one dose of GSK3036656 and had at least one evaluable PK sample. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	8	14	14	13
Median (Full Range); Unit of Measure: Hours
	1.500; (0.50 to 6.00)	2.492; (0.50 to 4.00)	1.000; (0.50 to 4.00)	2.000; (0.50 to 8.00)

11. Secondary Outcome

Title	Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Description	An adverse event 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. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.
Time Frame	Up to Day 28 (follow-up visit)

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	9	17	16	15
Measure Type: Count of Participants; Unit of Measure: Participants
Non-SAEs	14 77.8%	7 77.8%	14 82.4%	15 93.8%	9 60.0%
SAEs1	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

12. Secondary Outcome

Title	Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count
Description	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils, and platelet count. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title		Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:		All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed		18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: 10^9 cells per liter
Basophils	Number Analyzed	18 participants	8 participants	15 participants	15 participants	13 participants
		-0.006 (0.0281)	-0.009 (0.0242)	-0.018 (0.0248)	-0.003 (0.0263)	-0.005 (0.0267)
Eosinophils	Number Analyzed	18 participants	8 participants	15 participants	15 participants	13 participants
		0.086 (0.1383)	0.075 (0.1135)	0.088 (0.1239)	0.072 (0.0880)	0.057 (0.0642)
Lymphocytes	Number Analyzed	18 participants	8 participants	15 participants	15 participants	13 participants
		0.051 (0.3024)	-0.066 (0.3066)	0.157 (0.4010)	0.099 (0.5175)	0.136 (0.3861)
Monocytes	Number Analyzed	18 participants	8 participants	15 participants	15 participants	13 participants
		-0.073 (0.3236)	-0.156 (0.1467)	-0.125 (0.1376)	-0.301 (0.3647)	-0.242 (0.2225)
Total neutrophils	Number Analyzed	18 participants	8 participants	15 participants	15 participants	13 participants
		-0.940 (1.9563)	-0.509 (0.9609)	-0.613 (1.4654)	-1.633 (1.6475)	-0.949 (1.2011)
Platelet count	Number Analyzed	17 participants	8 participants	15 participants	15 participants	13 participants
		-59.6 (105.19)	-35.0 (83.00)	-93.6 (81.05)	-7.3 (81.33)	-78.6 (43.53)

13. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Hemoglobin
Description	Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: Grams per liter
	-3.4 (9.15)	-2.9 (6.64)	0.0 (7.32)	1.7 (9.21)	-4.6 (14.99)

14. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Hematocrit
Description	Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: Proportion of red blood cells in blood
	-0.012 (0.0308)	-0.008 (0.0225)	0.003 (0.0247)	0.007 (0.0277)	-0.018 (0.0454)

15. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Red Blood Cells Count
Description	Blood samples were collected to analyze the hematology parameter: red blood cells count. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: 10^12 cells per liter
	-0.130 (0.3067)	-0.091 (0.2776)	0.016 (0.2753)	0.059 (0.2875)	-0.216 (0.6590)

16. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Mean Corpuscular Volume
Description	Blood samples were collected to analyze the hematology parameter: mean corpuscular volume. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: Femtoliter
	0.2 (1.92)	-0.3 (0.89)	0.1 (1.36)	0.5 (0.92)	0.0 (1.35)

17. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
Description	Blood samples were collected to analyze the hematology parameter: mean corpuscle hemoglobin. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: Picograms
	0.2 (0.65)	-0.1 (0.64)	-0.1 (0.64)	0.1 (0.70)	0.3 (0.75)

18. Secondary Outcome

Title	Change From Baseline in Hematology Parameter: Reticulocytes
Description	Blood samples were collected to analyze the hematology parameter: reticulocytes. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: Percentage of reticulocytes
	0.0045 (0.00568)	0.0035 (0.00245)	0.0041 (0.00255)	0.0055 (0.00374)	0.0025 (0.00456)

19. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Potassium, Sodium, Blood Urea Nitrogen
Description	Blood samples were collected to analyze the chemistry parameters: glucose, calcium, chloride, potassium, sodium, and blood urea nitrogen. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: Millimoles per liter
Glucose	-0.29 (0.734)	0.05 (0.809)	0.17 (1.047)	-0.30 (0.902)	-0.86 (1.477)
Calcium	0.021 (0.0814)	-0.018 (0.1007)	-0.034 (0.0672)	0.005 (0.0633)	-0.024 (0.0860)
Chloride	1.1 (2.14)	1.0 (1.69)	1.6 (2.59)	2.3 (2.25)	2.3 (3.79)
Potassium	-0.39 (0.398)	-0.79 (0.925)	-0.47 (0.403)	-0.15 (0.521)	-0.28 (0.521)
Sodium	0.4 (2.33)	1.0 (1.60)	0.7 (2.55)	2.1 (3.49)	0.5 (3.10)
Blood urea nitrogen	-0.054 (0.3207)	-0.169 (0.5493)	0.125 (0.3074)	0.145 (0.2860)	0.042 (0.3198)

20. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Lactate Dehydrogenase (LDH), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT)
Description	Blood samples were collected to analyze the chemistry parameters: LDH, ALT, ALP, AST and GGT. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: International units per liter
LDH	-56.3 (57.81)	-52.8 (72.99)	-18.3 (36.22)	-26.5 (57.92)	-8.5 (73.83)
ALT	-20.6 (35.79)	-37.0 (62.35)	-8.1 (18.22)	-11.0 (18.60)	5.9 (20.77)
ALP	-3.1 (21.22)	-34.1 (61.88)	-16.8 (32.52)	-4.0 (70.73)	-7.5 (13.06)
AST	-13.7 (22.27)	-12.9 (13.94)	-5.6 (9.86)	-8.4 (13.47)	2.2 (8.74)
GGT	-3.9 (22.20)	-51.0 (76.64)	-14.9 (28.18)	-16.4 (30.83)	-5.2 (23.23)

21. Secondary Outcome

Title	Change From Baseline in Chemistry Parameters: Creatinine, Indirect Bilirubin, Direct Bilirubin and Total Bilirubin
Description	Blood samples were collected to analyze the chemistry parameters: creatinine, indirect bilirubin, direct bilirubin and total bilirubin. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title		Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:		All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed		18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: Micromoles per liter
Creatinine	Number Analyzed	18 participants	8 participants	15 participants	15 participants	13 participants
		0.6 (6.09)	2.8 (4.74)	3.1 (9.13)	1.5 (6.24)	0.6 (5.08)
Indirect bilirubin	Number Analyzed	15 participants	7 participants	15 participants	15 participants	13 participants
		-1.2 (1.08)	-0.9 (1.07)	-0.1 (1.51)	-1.1 (1.71)	0.3 (1.03)
Direct bilirubin	Number Analyzed	18 participants	8 participants	15 participants	15 participants	13 participants
		-0.6 (0.70)	-0.5 (1.07)	0.0 (0.76)	-0.7 (0.90)	-0.7 (1.38)
Total bilirubin	Number Analyzed	18 participants	8 participants	15 participants	15 participants	13 participants
		-1.5 (1.34)	-1.1 (1.81)	-0.1 (1.51)	-1.7 (2.05)	0.0 (1.58)

22. Secondary Outcome

Title	Change From Baseline in Chemistry Parameter: Total Protein
Description	Blood samples were collected to analyze the chemistry parameter: total protein. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: Grams per liter
	-1.7 (3.72)	-1.0 (6.46)	-1.3 (4.73)	2.2 (6.73)	-4.2 (5.83)

23. Secondary Outcome

Title	Number of Participants With Worst-Case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Description	Urine samples were collected to assess urine occult blood and urine protein. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as no change/decreased and increase to abnormal for urine occult blood and protein indicating proportional concentrations in the urine sample. 'No change/decreased' means no change from Baseline or a value less than the Baseline value. 'Increase to abnormal' means an increase from the Baseline value that is considered as an abnormal value. Baseline value is the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits. Data for worst-case post Baseline is presented.
Time Frame	Baseline (Day 1, Pre-dose) and up to Day 28 (follow-up visit)

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	9	17	16	15
Measure Type: Count of Participants; Unit of Measure: Participants
Occult blood: No change/decrease	15 83.3%	9 100.0%	16 94.1%	14 87.5%	9 60.0%
Occult blood: Increase to abnormal	3 16.7%	0 0.0%	1 5.9%	2 12.5%	6 40.0%
Protein: No change/decrease	8 44.4%	5 55.6%	9 52.9%	10 62.5%	9 60.0%
Protein: Increase to abnormal	10 55.6%	4 44.4%	8 47.1%	6 37.5%	6 40.0%

24. Secondary Outcome

Title	Number of Participants With Worst Case Vital Sign Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Description	Vital signs were measured in a semi-supine or supine position after 5 minutes rest. The PCI range for vital signs were: systolic blood pressure (SBP) (lower: <85 and upper: >160 milliliter of mercury [mmHg]); diastolic blood pressure (DBP) (lower: <45 and upper: >100 mmHg); heart rate (lower: <40 and upper: >110 beats per minute [bpm]); respiratory rate (lower: 10 and upper: 28 breaths per minutes) and temperature (lower: <35 and upper: >37.9 degrees Celsius). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high), unless there was no change in their category. Participants whose value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To w/in Range or No Change category". Participants were counted twice if the participant had values that changed "To Low" and "To High".
Time Frame	Up to Day 28 (follow-up visit)

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	9	17	16	15
Measure Type: Count of Participants; Unit of Measure: Participants
SBP: To low	1 5.6%	1 11.1%	0 0.0%	1 6.3%	0 0.0%
SBP: To within Range or No Change	17 94.4%	8 88.9%	17 100.0%	15 93.8%	15 100.0%
SBP: To High	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
DBP: To low	1 5.6%	1 11.1%	1 5.9%	0 0.0%	0 0.0%
DBP: To within Range or No Change	16 88.9%	7 77.8%	16 94.1%	16 100.0%	15 100.0%
DBP: To High	1 5.6%	1 11.1%	0 0.0%	0 0.0%	0 0.0%
Heart rate: To low	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Heart rate: To within Range or No Change	16 88.9%	6 66.7%	15 88.2%	15 93.8%	15 100.0%
Heart rate: To High	2 11.1%	3 33.3%	2 11.8%	1 6.3%	0 0.0%
Respiratory rate: To low	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Respiratory rate: To within Range or No Change	18 100.0%	9 100.0%	17 100.0%	13 81.3%	15 100.0%
Respiratory rate: To High	0 0.0%	0 0.0%	0 0.0%	3 18.8%	0 0.0%
Temperature: To low	0 0.0%	0 0.0%	0 0.0%	1 6.3%	0 0.0%
Temperature: To within Range or No Change	17 94.4%	7 77.8%	16 94.1%	14 87.5%	15 100.0%
Temperature: To High	1 5.6%	2 22.2%	1 5.9%	1 6.3%	0 0.0%

25. Secondary Outcome

Title	Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Description	Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, uncorrected QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with abnormal clinically significant ECG findings for worst case post-Baseline has been presented.
Time Frame	Up to Day 28 (follow-up visit)

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	9	15	16	15
Measure Type: Count of Participants; Unit of Measure: Participants
Abnormal, not clinically significant	13 72.2%	5 55.6%	12 80.0%	12 75.0%	10 66.7%
Abnormal - clinically significant	0 0.0%	0 0.0%	0 0.0%	1 6.3%	0 0.0%

26. Secondary Outcome

Title	Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)
Description	Twelve-lead ECGs were obtained to QTcF Interval and measured QT duration corrected for heart rate by Fridericia's formula interval. Baseline value was the latest assessment prior to Day 1 dose with a non-missing value, including those from unscheduled visits and the mean of the triplicate measurements at any given time point was used as the value for that time point. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit (Day 14) value.
Time Frame	Baseline (Day 1, Pre-dose) and at Day 14

Outcome Measure Data

Analysis Population Description

Safety Population consisted of all randomized participants who received at least one dose of study treatment. Only those participants with data available at specified time points were analyzed.

Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description:	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
Overall Number of Participants Analyzed	18	8	15	15	13
Mean (Standard Deviation); Unit of Measure: Milliseconds
	6.4 (13.64)	11.3 (14.40)	-1.8 (20.48)	9.5 (14.91)	4.0 (16.76)

Adverse Events

Time Frame	All-cause mortality, SAEs and non-SAEs were collected up to Day 28 (follow-up visit)
Adverse Event Reporting Description	Safety Population consisted of all randomized participants who received at least one dose of study treatment.
Arm/Group Title	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
Arm/Group Description	All participants received a standard-of-care therapy ( rifafour e-275) tablet, orally, once daily from Day 1 to Day 14. Participants received the standard treatment for tuberculosis (i.e. rifafour e-275 or equivalent generic alternative) once the study treatment (Day 1 to Day 14) was completed.	Participants received a loading dose of GSK3036656 3 milligram (mg), capsule, orally on Day 1, followed by maintenance dose of GSK3036656 1 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 15 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 5 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 30 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 15 mg, orally, once daily from Day 2 to Day 14.	Participants received a loading dose of GSK3036656 75 mg, capsule, orally on Day 1, followed by maintenance dose of GSK3036656 30 mg, orally, once daily from Day 2 to Day 14.
All-Cause Mortality
	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Serious Adverse Events
	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Rifafour e-275	GSK3036656 1 mg	GSK3036656 5 mg	GSK3036656 15 mg	GSK3036656 30 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	14/18 (77.78%)	7/9 (77.78%)	14/17 (82.35%)	15/16 (93.75%)	9/15 (60.00%)
Blood and lymphatic system disorders
Anaemia † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Thrombocytopenia † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Neutropenia † 1	0/18 (0.00%)	0/9 (0.00%)	2/17 (11.76%)	0/16 (0.00%)	0/15 (0.00%)
Cardiac disorders
Palpitations † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Ventricular hypokinesia † 1	0/18 (0.00%)	1/9 (11.11%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Ear and labyrinth disorders
Ear pain † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Noninfective myringitis † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Eye disorders
Eye irritation † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	1/15 (6.67%)
Uveitis † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	3/18 (16.67%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	2/15 (13.33%)
Dyspepsia † 1	0/18 (0.00%)	1/9 (11.11%)	1/17 (5.88%)	1/16 (6.25%)	1/15 (6.67%)
Nausea † 1	2/18 (11.11%)	0/9 (0.00%)	0/17 (0.00%)	2/16 (12.50%)	0/15 (0.00%)
Vomiting † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	1/16 (6.25%)	2/15 (13.33%)
Diarrhoea † 1	1/18 (5.56%)	0/9 (0.00%)	2/17 (11.76%)	0/16 (0.00%)	0/15 (0.00%)
Odynophagia † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
General disorders
Chest pain † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Injection site pain † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Peripheral swelling † 1	0/18 (0.00%)	1/9 (11.11%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Pyrexia † 1	0/18 (0.00%)	1/9 (11.11%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Vessel puncture site pain † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Immune system disorders
Hypersensitivity † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Infections and infestations
Carbuncle † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	1/15 (6.67%)
Conjunctivitis † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Fungal skin infection † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Gastroenteritis † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	1/15 (6.67%)
Otitis externa † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Pulmonary tuberculosis † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Tinea versicolour † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Injury, poisoning and procedural complications
Arthropod bite † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Skin abrasion † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Thermal burn † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	1/15 (6.67%)
Investigations
Blood pressure increased † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Ejection fraction decreased † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	1/15 (6.67%)
Electrocardiogram PR prolongation † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/18 (11.11%)	0/9 (0.00%)	1/17 (5.88%)	4/16 (25.00%)	0/15 (0.00%)
Myalgia † 1	1/18 (5.56%)	1/9 (11.11%)	0/17 (0.00%)	2/16 (12.50%)	0/15 (0.00%)
Back pain † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	1/15 (6.67%)
Musculoskeletal pain † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Nervous system disorders
Headache † 1	3/18 (16.67%)	2/9 (22.22%)	1/17 (5.88%)	2/16 (12.50%)	1/15 (6.67%)
Dizziness † 1	2/18 (11.11%)	1/9 (11.11%)	1/17 (5.88%)	1/16 (6.25%)	0/15 (0.00%)
Neuropathy peripheral † 1	0/18 (0.00%)	1/9 (11.11%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Somnolence † 1	0/18 (0.00%)	1/9 (11.11%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Psychiatric disorders
Insomnia † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis † 1	2/18 (11.11%)	0/9 (0.00%)	5/17 (29.41%)	2/16 (12.50%)	1/15 (6.67%)
Pleuritic pain † 1	1/18 (5.56%)	0/9 (0.00%)	2/17 (11.76%)	1/16 (6.25%)	0/15 (0.00%)
Dry throat † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Nasal congestion † 1	0/18 (0.00%)	1/9 (11.11%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Rhinorrhoea † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Skin and subcutaneous tissue disorders
Pruritus † 1	2/18 (11.11%)	2/9 (22.22%)	1/17 (5.88%)	4/16 (25.00%)	0/15 (0.00%)
Rash pruritic † 1	2/18 (11.11%)	1/9 (11.11%)	0/17 (0.00%)	0/16 (0.00%)	1/15 (6.67%)
Rash papular † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	2/16 (12.50%)	0/15 (0.00%)
Skin hypopigmentation † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	1/15 (6.67%)
Acne † 1	0/18 (0.00%)	0/9 (0.00%)	1/17 (5.88%)	0/16 (0.00%)	0/15 (0.00%)
Blister † 1	0/18 (0.00%)	1/9 (11.11%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Skin exfoliation † 1	0/18 (0.00%)	0/9 (0.00%)	0/17 (0.00%)	1/16 (6.25%)	0/15 (0.00%)
Vascular disorders
Flushing † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
Orthostatic hypotension † 1	1/18 (5.56%)	0/9 (0.00%)	0/17 (0.00%)	0/16 (0.00%)	0/15 (0.00%)
1 Term from vocabulary, MedDRA 24.1; † 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):

Volynets GP, Usenko MO, Gudzera OI, Starosyla SA, Balanda AO, Syniugin AR, Gorbatiuk OB, Prykhod'ko AO, Bdzhola VG, Yarmoluk SM, Tukalo MA. Identification of dual-targeted Mycobacterium tuberculosis aminoacyl-tRNA synthetase inhibitors using machine learning. Future Med Chem. 2022 Sep;14(17):1223-1237. doi: 10.4155/fmc-2022-0085. Epub 2022 Jul 25.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03557281
• Other Study ID Numbers: 201214
• First Submitted: June 4, 2018
• First Posted: June 15, 2018
• Results First Submitted: November 17, 2022
• Results First Posted: October 26, 2023
• Last Update Posted: October 26, 2023