Trial Outcomes & Findings for Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis (NCT NCT00864383)

Last Updated: 2017-03-21

Results Overview

The primary efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome). Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis. For the final 18 month study visit when both L-J samples were contaminated or missing, if the subject could not be brought back, liquid medium culture results were used in place of solid medium culture results.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1931 participants

Primary outcome timeframe

18 months (within one year of completion of therapy)

Results posted on

2017-03-21

Participant Flow

Participant milestones

Participant milestones
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Per- Protocol STARTED	640	655	636
Per- Protocol COMPLETED	510	514	524
Per- Protocol NOT COMPLETED	130	141	112
Modified Intent to Treat STARTED	640	655	636
Modified Intent to Treat COMPLETED	555	568	551
Modified Intent to Treat NOT COMPLETED	85	87	85

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=510 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR (Isoniazid) n=514 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR (Ethambutol) n=524 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Total n=1548 Participants Total of all reporting groups
Age, Customized < 25 years	160 participants n=5 Participants	162 participants n=7 Participants	146 participants n=5 Participants	468 participants n=4 Participants
Age, Customized 25-35 years	145 participants n=5 Participants	162 participants n=7 Participants	175 participants n=5 Participants	482 participants n=4 Participants
Age, Customized > 35 years	205 participants n=5 Participants	190 participants n=7 Participants	203 participants n=5 Participants	598 participants n=4 Participants
Sex: Female, Male Female	154 Participants n=5 Participants	163 Participants n=7 Participants	155 Participants n=5 Participants	472 Participants n=4 Participants
Sex: Female, Male Male	356 Participants n=5 Participants	351 Participants n=7 Participants	369 Participants n=5 Participants	1076 Participants n=4 Participants
Race/Ethnicity, Customized Black	238 participants n=5 Participants	210 participants n=7 Participants	237 participants n=5 Participants	685 participants n=4 Participants
Race/Ethnicity, Customized Asian	160 participants n=5 Participants	154 participants n=7 Participants	161 participants n=5 Participants	475 participants n=4 Participants
Race/Ethnicity, Customized Mixed race	111 participants n=5 Participants	148 participants n=7 Participants	126 participants n=5 Participants	385 participants n=4 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Weight group < 40 kg	50 participants n=5 Participants	44 participants n=7 Participants	58 participants n=5 Participants	152 participants n=4 Participants
Weight group 40-45 kg	80 participants n=5 Participants	90 participants n=7 Participants	82 participants n=5 Participants	252 participants n=4 Participants
Weight group > 45-55 kg	206 participants n=5 Participants	210 participants n=7 Participants	204 participants n=5 Participants	620 participants n=4 Participants
Weight group > 55-75 kg	161 participants n=5 Participants	158 participants n=7 Participants	174 participants n=5 Participants	493 participants n=4 Participants
Weight group > 75 kg	13 participants n=5 Participants	12 participants n=7 Participants	6 participants n=5 Participants	31 participants n=4 Participants
Smoking status Never	246 participants n=5 Participants	231 participants n=7 Participants	230 participants n=5 Participants	707 participants n=4 Participants
Smoking status Past	119 participants n=5 Participants	111 participants n=7 Participants	134 participants n=5 Participants	364 participants n=4 Participants
Smoking status Current	145 participants n=5 Participants	172 participants n=7 Participants	160 participants n=5 Participants	477 participants n=4 Participants
HIV positivity	38 participants n=5 Participants	37 participants n=7 Participants	35 participants n=5 Participants	110 participants n=4 Participants
Drug resistance Isoniazid	29 participants n=5 Participants	34 participants n=7 Participants	39 participants n=5 Participants	102 participants n=4 Participants
Drug resistance Pyrazinamide	14 participants n=5 Participants	7 participants n=7 Participants	6 participants n=5 Participants	27 participants n=4 Participants
Cavitation	368 participants n=5 Participants	357 participants n=7 Participants	367 participants n=5 Participants	1092 participants n=4 Participants
Time to positivity on MGIT sputum culture ≥ 5 days	266 participants n=5 Participants	263 participants n=7 Participants	258 participants n=5 Participants	787 participants n=4 Participants
Time to positivity on MGIT sputum culture < 5 days	229 participants n=5 Participants	239 participants n=7 Participants	254 participants n=5 Participants	722 participants n=4 Participants
Time to positivity on MGIT sputum culture Not available	15 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	39 participants n=4 Participants

PRIMARY outcome

Timeframe: 18 months (within one year of completion of therapy)

Population: Per protocol population

Outcome measures

Outcome measures
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=510 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=514 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=524 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ).	43 participants with failure or relapse	78 participants with failure or relapse	105 participants with failure or relapse

PRIMARY outcome

Timeframe: 18 months (within one year of completion of therapy)

Population: Safety population, defined as all subjects who underwent randomization and who received at least on dose of study drug.

The number of participants includes all patients who had at least one grade 3 or 4 adverse event.

Outcome measures

Outcome measures
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=639 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=655 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=636 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Number of Patients With Grade 3 or 4 Adverse Events (Using a Modified Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases [DAIDS] Scale of Adverse Event Reporting)	123 participants with Grade 3 or 4 AEs	127 participants with Grade 3 or 4 AEs	111 participants with Grade 3 or 4 AEs

SECONDARY outcome

Timeframe: 18 months (within one year of completion of therapy)

Population: Per protocol population

The secondary analysis of efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome) based on MGIT. Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis.

Outcome measures

Outcome measures
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=498 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=498 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=512 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT).	65 participants with failure or relapse	98 participants with failure or relapse	131 participants with failure or relapse

SECONDARY outcome

Timeframe: 8 weeks

Population: Per protocol

Number of patients who are TB LJ culture negative at 8 weeks.

Outcome measures

Outcome measures
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=422 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=457 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=458 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Number of Patients Who Are Culture Negative (Solid LJ Culture)	352 participants who are culture negative	394 participants who are culture negative	401 participants who are culture negative

SECONDARY outcome

Timeframe: 8 weeks

Number of patients who are TB MGIT culture negative at 8 weeks.

Outcome measures

Outcome measures
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=419 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=440 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=429 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Number of Patients Who Are Culture Negative (Liquid MGIT Culture)	235 participants who are culture negative	274 participants who are culture negative	260 participants who are culture negative

SECONDARY outcome

Timeframe: 18 months

Population: All randomized patients excluding late screen failures

Culture negative for TB using LJ cultures.

Outcome measures

Outcome measures
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=600 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=617 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=604 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Time to First Culture Negative Sputum Sample (LJ Solid Media)	6.0 Time to culture negative status / weeks Interval 6.0 to 6.1	6.0 Time to culture negative status / weeks Interval 5.1 to 6.0	6.0 Time to culture negative status / weeks Interval 5.7 to 6.0

SECONDARY outcome

Timeframe: 18 months

Population: All randomized patients excluding late screen failures

Outcome measures

Outcome measures
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=600 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=617 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=604 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Time to First Culture Negative Sputum Sample (MGIT Liquid Media)	11.9 Time to culture negative status / weeks Interval 8.1 to 12.0	8.0 Time to culture negative status / weeks Interval 8.0 to 9.9	8.0 Time to culture negative status / weeks Interval 8.0 to 8.1

SECONDARY outcome

Timeframe: 18 months

Population: All randomized subjects.

Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Unfavorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result ("isolated positive culture") was followed by at least two negative culture results.

Outcome measures

Outcome measures
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=640 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=655 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=636 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media.	172 participants with unfavorable outcome	219 participants with unfavorable outcome	217 participants with unfavorable outcome

SECONDARY outcome

Timeframe: 18 months

Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Favorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result ("isolated positive culture") was followed by at least two negative culture results.

Outcome measures

Outcome measures
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=640 Participants * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=655 Participants * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=636 Participants * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media.	87 participants with unfavorable outcome	132 participants with unfavorable outcome	132 participants with unfavorable outcome

Adverse Events

Regimen 1 - 2EHRZ/4HR (Control Regimen)

Serious events: 38 serious events

Other events: 507 other events

Deaths: 0 deaths

Regimen 2 - 2MHRZ/2MHR

Serious events: 46 serious events

Other events: 537 other events

Deaths: 0 deaths

Regimen 3 - 2EMRZ/2MR

Serious events: 40 serious events

Other events: 522 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Daniel E. Everitt, MD, Vice President and Senior Medical Officer

Global Alliance for TB Drug Development

Phone: (212) 227-7540

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=639 participants at risk * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=655 participants at risk * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=636 participants at risk * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Gastrointestinal disorders Abdominal Distension	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Abdominal Mass	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Abdominal Pain	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/636 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/655 • Number of events 3 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Abdominal Tenderness	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Acute Abdomen	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Ascites	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Diarrhoea	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Gastrointestinal Disorder	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Haematemesis	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Haematochezia	0.16% 1/639 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Nausea	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/655 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/636 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Pancreatitis	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Peptic Ulcer Perforation	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Gastrointestinal disorders Vomiting	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.46% 3/655 • Number of events 3 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.94% 6/636 • Number of events 11 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Infections and infestations Appendicitis	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Infections and infestations Diarrhoea Infectious	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Infections and infestations Disseminated Tuberculosis	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Infections and infestations Gangrene	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Infections and infestations Hepatitis B	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Aspartate Aminotransferase Increased	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Blood Bilirubin Increased	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Blood Creatinine Increased	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Breath Sounds Abnormal	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Gamma- Glutamyltransferase Increased	0.31% 2/639 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/636 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Haemoglobin Decreased	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Hepatic Enzyme Increased	0.47% 3/639 • Number of events 3 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.46% 3/655 • Number of events 3 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.63% 4/636 • Number of events 4 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations International Normalised Ratio Increased	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Liver Function Test Abnormal	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Prothrombin Time prolonged	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Investigations Respiratory Rate Increased	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Respiratory, thoracic and mediastinal disorders Asphyxia	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Respiratory, thoracic and mediastinal disorders Cough	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.78% 5/639 • Number of events 6 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/655 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.94% 6/636 • Number of events 8 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.1% 7/639 • Number of events 8 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.92% 6/655 • Number of events 7 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/636 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Respiratory, thoracic and mediastinal disorders Hydropneumothorax	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 3 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.

Other adverse events
Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n=639 participants at risk * Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by * Nine weeks of Isoniazid and Rifampicin only. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 2 - 2MHRZ/2MHR n=655 participants at risk * Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by * Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo. Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.	Regimen 3 - 2EMRZ/2MR n=636 participants at risk * Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by * Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by * Nine weeks of the Isoniazid placebo and the Rifampicin placebo Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide \& Rifampicin: Moxifloxacin 400 mg Rifampicin \< 45 kg 450 mg \> 45 kg 600 mg Isoniazid 300 mg Pyrazinamide \< 40 kg 25 mg/kg rounded to nearest 500 mg\* 40-55 kg 1000 mg \> 55 kg - 75 kg 1500 mg \> 75 kg 2000 mg Ethambutol \< 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg \> 55 kg - 75 kg 1200 mg \> 75 kg 1600 mg \*For pyrazinamide dosing in patients \< 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.
Blood and lymphatic system disorders Abdominal Lymphadenopathy	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Anaemia	1.6% 10/639 • Number of events 17 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	2.0% 13/655 • Number of events 16 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	1.3% 8/636 • Number of events 11 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Hypochromic Anaemia	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Iron Deficiency Anaemia	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Leukocytosis	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Leukopenia	1.3% 8/639 • Number of events 13 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	1.4% 9/655 • Number of events 12 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	1.4% 9/636 • Number of events 12 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Lymph Node Pain	0.31% 2/639 • Number of events 7 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Lymphadenitis	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Lymphadenopathy	6.7% 43/639 • Number of events 61 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	6.7% 44/655 • Number of events 71 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	7.9% 50/636 • Number of events 68 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Lymphopenia	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Microcytic Anaemia	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Monocytosis	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Neutropenia	0.63% 4/639 • Number of events 13 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.46% 3/655 • Number of events 6 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/636 • Number of events 5 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Neutrophilia	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Thrombocytopenia	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/636 • Number of events 3 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Arrhythmia	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Bradycardia	0.31% 2/639 • Number of events 3 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Cardiac Failure	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Cardiac Failure Congestive	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Congestive Cardiomyopathy	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Cor Pulmonale	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Hyperdynamic Left Ventricle	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Left Ventricular Hypertrophy	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Palpitations	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.61% 4/655 • Number of events 5 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/636 • Number of events 6 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Pericardial Disease	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Sinus Tachycardia	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Tachyarrhythmia	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Tachycardia	6.3% 40/639 • Number of events 54 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	7.3% 48/655 • Number of events 71 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	6.1% 39/636 • Number of events 45 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Cardiac disorders Ventricular Hypertrophy	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Ear and labyrinth disorders Auricular Swelling	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Ear and labyrinth disorders Cerumen Impaction	1.6% 10/639 • Number of events 13 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.76% 5/655 • Number of events 7 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	1.3% 8/636 • Number of events 8 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Ear and labyrinth disorders Deafness	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.31% 2/655 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Ear and labyrinth disorders Ear Canal Erythema	0.31% 2/639 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Ear and labyrinth disorders Ear Discomfort	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Ear and labyrinth disorders Ear Pain	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.46% 3/655 • Number of events 4 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.79% 5/636 • Number of events 7 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Ear and labyrinth disorders Ear Pruritus	0.31% 2/639 • Number of events 2 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.15% 1/655 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Ear and labyrinth disorders Haematotympanum	0.00% 0/639 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.16% 1/636 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.
Ear and labyrinth disorders Hearing Impaired	0.16% 1/639 • Number of events 1 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/655 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.	0.00% 0/636 Total Number of SAE events and the number and percentage of subjects experiencing each event by system organ class.