Trial Outcomes & Findings for A Study to Learn How Well Nifurtimox Works and How Safe it is in Children Aged 0 to 17 Years With Chagas' Disease, an Inflammatory, Infectious Disease Caused by the Parasite Trypanosoma Cruzi (NCT NCT02625974)

Results Overview

Cure is defined as sero-reduction (in subjects ≥8 months to \<18 years of age at randomization) or sero-conversion (in all subjects). Sero-reduction is defined as a ≥20% reduction in optical density \[OD\]) measured by two conventional ELISA serology tests and sero-conversion is defined as negative Immunoglobulin G (IgG) concentration measured by two conventional ELISA serology tests. Subjects who have missing conventional serology results at the 12 month time point were treated as failures (ie, no cure). For the primary objective in the study, superiority over placebo was confirmed if the lower limit of the 95% Confidence Interval (CI) for the nifurtimox (60-day regimen) cure rate is greater than 16%, the larger of the upper limits of the 95% CIs for historical placebo control.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

330 participants

Primary outcome timeframe

At 12 months post-treatment

Results posted on

2024-08-19

Participant Flow

Part 1 of the study was conducted from 27 JAN 2016 (First subject first visit) to 25 JUL 2018 (Last subject last visit) in Argentina, Bolivia and Colombia. Part 2 of the study was conducted from 26 SEP 2018 (First subject first visit) to 10 AUG 2021 (Last subject last visit) in Argentina, Bolivia and Colombia.

Part 1: 330 subjects who were eligible to participate in the study were randomized in a 2:1 ratio to either a 60-Day or 30-Day regimen with nifurtimox tablets. 308 subjects completed treatment in Part 1, and 318 subjects completed Part 1. Part 2: Of the 318 subjects completed Part 1, 295 subjects were included in Part 2.

Participant milestones

Participant milestones
Measure	Nifurtimox 60 Days / Arm 1 Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)
Part 1 STARTED	219	111
Part 1 Received Treatment	219	111
Part 1 COMPLETED	210	108
Part 1 NOT COMPLETED	9	3
Part 2 STARTED	197	98
Part 2 COMPLETED	191	91
Part 2 NOT COMPLETED	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Nifurtimox 60 Days / Arm 1 Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)
Part 1 Lost to Follow-up	9	3
Part 2 Lost to Follow-up	4	6
Part 2 Other, including due to the COVID-19 Pandemic	2	1

Baseline Characteristics

A Study to Learn How Well Nifurtimox Works and How Safe it is in Children Aged 0 to 17 Years With Chagas' Disease, an Inflammatory, Infectious Disease Caused by the Parasite Trypanosoma Cruzi

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Total n=330 Participants Total of all reporting groups
Age, Customized 0 to 27 days	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Age, Customized 28 days to younger than 8 months	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Age, Customized 8 months to younger than 2 years	8 Participants n=5 Participants	17 Participants n=7 Participants	25 Participants n=5 Participants
Age, Customized 2 years to younger than 18 years	96 Participants n=5 Participants	190 Participants n=7 Participants	286 Participants n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	119 Participants n=7 Participants	178 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	100 Participants n=7 Participants	152 Participants n=5 Participants
Race/Ethnicity, Customized White	81 Participants n=5 Participants	155 Participants n=7 Participants	236 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska native	30 Participants n=5 Participants	64 Participants n=7 Participants	94 Participants n=5 Participants
Total Purified Antigen enzyme-linked immunosorbent assay (ELISA) test results Reactive	110 Participants n=5 Participants	219 Participants n=7 Participants	329 Participants n=5 Participants
Total Purified Antigen enzyme-linked immunosorbent assay (ELISA) test results Non Reactive	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Total Purified Antigen ELISA optical density (OD) values	1.532 No dimension STANDARD_DEVIATION 0.533 • n=5 Participants	1.474 No dimension STANDARD_DEVIATION 0.553 • n=7 Participants	1.494 No dimension STANDARD_DEVIATION 0.546 • n=5 Participants
Recombinant ELISA test results Reactive	110 Participants n=5 Participants	219 Participants n=7 Participants	329 Participants n=5 Participants
Recombinant ELISA test results Non Reactive	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Recombinant ELISA OD values	2.765 No dimension STANDARD_DEVIATION 0.605 • n=5 Participants	2.735 No dimension STANDARD_DEVIATION 0.640 • n=7 Participants	2.745 No dimension STANDARD_DEVIATION 0.628 • n=5 Participants
Non conventional ELISA-F29 test results Reactive	72 Participants n=5 Participants	142 Participants n=7 Participants	214 Participants n=5 Participants
Non conventional ELISA-F29 test results Non Reactive	39 Participants n=5 Participants	77 Participants n=7 Participants	116 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	108 Participants n=5 Participants	217 Participants n=7 Participants	325 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Concentration test for T. cruzi Positive	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
Concentration test for T. cruzi Negative	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Concentration test for T. cruzi Missing	104 Participants n=5 Participants	207 Participants n=7 Participants	311 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 12 months post-treatment

Cure is defined as sero-reduction (in subjects ≥8 months to \<18 years of age at randomization) or sero-conversion (in all subjects). Sero-reduction is defined as a ≥20% reduction in optical density \[OD\]) measured by two conventional ELISA serology tests and sero-conversion is defined as negative Immunoglobulin G (IgG) concentration measured by two conventional ELISA serology tests. Subjects who have missing conventional serology results at the 12 month time point were treated as failures (ie, no cure). For the primary objective in the study, superiority over placebo was confirmed if the lower limit of the 95% Confidence Interval (CI) for the nifurtimox (60-day regimen) cure rate is greater than 16%, the larger of the upper limits of the 95% CIs for historical placebo control.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Percentage of Sero-reduction or Sero-conversion (Cured Subjects)	32.9 Percentage of subjects Interval 26.4 to 39.3	18.9 Percentage of subjects Interval 11.2 to 26.7	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1

Seronegative conversion measured by two types of assay (recombinant ELISA and indirect hemagglutination assay \[IHA\]) in subjects who were randomized and received at least one dose of the 60-day nifurtimox treatment regimen compared to an external control group of historical placebo patients with Chagas' disease. Incidence rate is the number of new cases of seronegative conversion over the study period (i.e., 4 years after end of nifurtimox treatment) divided by the person-time at risk. It was modelled using a Poisson distribution with a 2-sided 95% exact CI. Number of participants with events were reported.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=197 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 2 - Incidence Rate of Seronegative Conversion in Subjects Received at Least One Dose of the 60-day Nifurtimox Treatment Regimen.	16 Participants	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At Visit 2 (Day 1): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours

Measured in sub-population.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=40 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=23 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 2 5 - 10 MIN POST	NA ug/L Interval to 154.8 below the level of detection	21.1 ug/L Interval to 695.0 below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 2 10 - 120 MIN POST	78.2 ug/L Interval 5.8 to 847.5	49.0 ug/L Interval to 524.3 below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 2 Predose	NA ug/L Interval to 26.8 below the level of detection	NA ug/L below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 2 2 - 4 HOURS POST	215.4 ug/L Interval 77.9 to 516.3	300.7 ug/L Interval 106.9 to 533.5	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 2 4 - 8 HOURS POST	267.6 ug/L Interval 40.2 to 508.1	289.6 ug/L Interval 103.2 to 301.0	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At Visit 3 (Day 7): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours

Measured in sub-population.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=40 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=22 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 3 Predose	47.7 ug/L Interval to 407.6 below the level of detection	38.3 ug/L Interval to 472.3 below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 3 5 - 10 MIN POST	82.6 ug/L Interval to 561.6 below the level of detection	56.0 ug/L Interval to 442.8 below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 3 10 - 120 MIN POST	250.6 ug/L Interval 13.8 to 1035.6	232.3 ug/L Interval 13.9 to 706.3	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 3 2 - 4 HOURS POST	497.2 ug/L Interval 57.1 to 1027.4	257.7 ug/L Interval 46.3 to 660.2	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 3 4 - 8 HOURS POST	427.5 ug/L Interval 141.2 to 778.2	267.0 ug/L Interval to 339.6 below the level of detection	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At Visit 6 (Day 30): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours

The evaluation was based on clinical examinations. Measured in sub-population.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=35 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=24 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 6 Predose	23.8 ug/L Interval to 459.3 below the level of detection	40.8 ug/L Interval to 284.3 below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 6 5 - 10 MIN POST	71.7 ug/L Interval to 153.7 below the level of detection	73.7 ug/L Interval to 266.7 below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 6 10 - 120 MIN POST	135.0 ug/L Interval to 932.4 below the level of detection	172.7 ug/L Interval 14.1 to 387.3	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 6 2 - 4 HOURS POST	369.5 ug/L Interval 92.1 to 1277.0	103.8 ug/L Interval 12.3 to 1107.2	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 6 4 - 8 HOURS POST	249.7 ug/L Interval 70.9 to 504.3	165.2 ug/L Interval 84.9 to 1089.3	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At Visit 8 (Day 60): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours

Measured in sub-population.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=36 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=19 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 8 Predose	NA ug/L Interval to 258.7 below the level of detection	NA ug/L below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 8 5 - 10 MIN POST	92.4 ug/L Interval 15.9 to 255.1	NA ug/L below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 8 10 - 120 MIN POST	139.1 ug/L Interval 23.6 to 711.4	NA ug/L Interval to 21.5 below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 8 2 - 4 HOURS POST	395.6 ug/L Interval 166.9 to 883.0	NA ug/L below the level of detection	—	—	—	—	—	—	—	—	—	—
Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 8 4 - 8 HOURS POST	300.6 ug/L Interval 28.5 to 1217.2	NA ug/L below the level of detection	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1

Seronegative conversion measured by two types of assay (recombinant ELISA and indirect hemagglutination assay \[IHA\]) in subjects who were randomized and received at least one dose of the 30-day nifurtimox treatment regimen. Incidence rate is the number of new cases of seronegative conversion over the study period (i.e., 4 years after end of nifurtimox treatment) divided by the person-time at risk. It was modelled using a Poisson distribution with a 2-sided 95% exact CI. Number of participants with events were reported.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=98 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 2 - Incidence Rate of Seronegative Conversion in Subjects Who Received at Least One Dose of the 30-day Nifurtimox Treatment Regimen	8 Participants	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1

Summary of subjects by evidence of established Chagas-related cardiomyopathy as measured by electrocardiogram (ECG). Evidence of established Chagas-related cardiomyopathy: Total

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=197 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=98 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 2 - ECG Signs of Established Chagas-related Cardiomyopathy YES	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - ECG Signs of Established Chagas-related Cardiomyopathy NO	189 Participants	90 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - ECG Signs of Established Chagas-related Cardiomyopathy MISSING	8 Participants	8 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1

Summary of subjects by evidence of established Chagas-related cardiomyopathy as measured by Serological response. Evidence of established Chagas-related cardiomyopathy: Total

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=197 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=98 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 2 - Serological Response of Established Chagas-related Cardiomyopathy Non Reactive	14 Participants	6 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - Serological Response of Established Chagas-related Cardiomyopathy Reactive	176 Participants	84 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - Serological Response of Established Chagas-related Cardiomyopathy Missing	7 Participants	8 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1

Summary and change from baseline of optical density values measured by total purified antigen ELISA. Optical density is the measure of absorbance, and is defined as the ratio of the intensity of light falling upon a material and the intensity transmitted.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=197 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=98 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA Part 1 - Baseline (Visit 1)	1.47 Optical density Standard Deviation 0.55 • Interval 0.55 to 2.6	1.52 Optical density Standard Deviation 0.55 • Interval 0.55 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA Part 2 - Year 2: Change from Baseline (FU Visit 1)	-0.25 Optical density Standard Deviation 0.41 • Interval 0.41 to	-0.23 Optical density Standard Deviation 0.49 • Interval 0.49 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA Part 1 - Up to 420 days post-treatment (Visit 11)	1.24 Optical density Standard Deviation 0.62 • Interval 0.62 to 2.5	1.30 Optical density Standard Deviation 0.61 • Interval 0.61 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA Part 1 - Change from Baseline (Visit 11)	-0.24 Optical density Standard Deviation 0.29 • Interval 0.29 to 0.3	-0.23 Optical density Standard Deviation 0.41 • Interval 0.41 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA Part 2 - Year 2: (FU Visit 1)	1.23 Optical density Standard Deviation 0.59 • Interval 0.59 to	1.29 Optical density Standard Deviation 0.61 • Interval 0.61 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA Part 2 - Year 3 (FU Visit 3)	1.16 Optical density Standard Deviation 0.58 • Interval 0.58 to	1.23 Optical density Standard Deviation 0.58 • Interval 0.58 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA Part 2 - Year 3: Change from Baseline (FU Visit 3)	-0.30 Optical density Standard Deviation 0.42 • Interval 0.42 to	-0.30 Optical density Standard Deviation 0.50 • Interval 0.5 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA Part 2 - Year 4 (FU Visit 5)	1.12 Optical density Standard Deviation 0.57 • Interval 0.57 to	1.23 Optical density Standard Deviation 0.59 • Interval 0.59 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA Part 2 - Year 4: Change from Baseline (FU Visit 5)	-0.35 Optical density Standard Deviation 0.40 • Interval 0.4 to	-0.30 Optical density Standard Deviation 0.46 • Interval 0.46 to	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1

Summary and change from baseline of optical density values measured by recombinant ELISA. Optical density is the measure of absorbance, and is defined as the ratio of the intensity of light falling upon a material and the intensity transmitted.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=197 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=98 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA Part 2 - Year 2: Change from Baseline (FU Visit 1)	-0.23 Optical density Standard Deviation 0.87 • Interval 0.87 to	-0.17 Optical density Standard Deviation 0.90 • Interval 0.9 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA Part 2 - Year 3 (FU Visit 3)	2.17 Optical density Standard Deviation 0.98 • Interval 0.98 to	2.25 Optical density Standard Deviation 0.91 • Interval 0.91 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA Part 2 - Year 3: Change from Baseline (FU Visit 3)	-0.56 Optical density Standard Deviation 0.86 • Interval 0.86 to	-0.45 Optical density Standard Deviation 0.87 • Interval 0.87 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA Part 2 - Year 4 (FU Visit 5)	2.09 Optical density Standard Deviation 1.01 • Interval 1.01 to	2.22 Optical density Standard Deviation 1.00 • Interval 1.0 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA Part 2 - Year 4: Change from Baseline (FU Visit 5)	-0.64 Optical density Standard Deviation 0.89 • Interval 0.89 to	-0.48 Optical density Standard Deviation 0.87 • Interval 0.87 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA Part 1 - Baseline (Visit 1)	2.74 Optical density Standard Deviation 0.63 • Interval 0.63 to	2.73 Optical density Standard Deviation 0.63 • Interval 0.63 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA Part 1 - Up to 420 days post-treatment (Visit 11)	2.27 Optical density Standard Deviation 0.98 • Interval 0.98 to	2.31 Optical density Standard Deviation 1.00 • Interval 1.0 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA Part 1 - Change from Baseline (Visit 11)	-0.47 Optical density Standard Deviation 0.74 • Interval 0.74 to	-0.41 Optical density Standard Deviation 0.79 • Interval 0.79 to	—	—	—	—	—	—	—	—	—	—
Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA Part 2 - Year 2: (FU Visit 1)	2.5 Optical density Standard Deviation 0.95 • Interval 0.95 to	2.57 Optical density Standard Deviation 0.88 • Interval 0.88 to	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At Visit 1 (before treatment started)

The evaluation was based on clinical examinations.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 1	2 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 7 days (Visit 3)

The evaluation was based on clinical examinations.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 3 Anemia	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 3 Chagas disease	2 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 3 Hepatomegaly	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 3 Known ECG abnormality	4 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 30 days (Visit 6)

The evaluation was based on clinical examinations.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=215 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=110 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 6 Known ECG abnormality	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 6 Romana sign	0 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 60 days (Visit 8; end of treatment)

The evaluation was based on clinical examinations.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=217 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=109 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 8 Anemia	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 8 Chagas disease	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 8 Known ECG abnormality	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 8 Lymphadenopathy	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 90 days (Visit 9 post-treatment)

The evaluation was based on clinical examinations.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=213 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=107 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 9	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 240 days (Visit 10 post-treatment)

The evaluation was based on clinical examinations.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=212 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=109 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 10	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

The evaluation was based on clinical examinations.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=210 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=108 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 11	3 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 90 days (Visit 9 post-treatment)

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=12 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=7 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 1\|Positive	12 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 3\|Positive	1 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 6\|Positive	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 8\|Positive	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 9\|Positive	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 1\|Negative	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 3\|Negative	11 Participants	5 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 6\|Negative	12 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 8\|Negative	12 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 9\|Negative	11 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 1\|Missing	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 3\|Missing	0 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 6\|Missing	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 8\|Missing	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) Visit 9\|Missing	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

The non-conventional ELISA-F29 test is considered an early marker of treatment efficacy in chronic Chagas disease.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With a Positive Serological Response Using Non-conventional Enzyme-linked Immunosorbent Assay-F29 (ELISAF29) Test Reactive	96 Participants	54 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With a Positive Serological Response Using Non-conventional Enzyme-linked Immunosorbent Assay-F29 (ELISAF29) Test Non-reactive	114 Participants	54 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With a Positive Serological Response Using Non-conventional Enzyme-linked Immunosorbent Assay-F29 (ELISAF29) Test Missing	9 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

The qPCR is molecular technique, considered a tool to diagnose acute and congenital Chagas disease, as well as a marker to measure treatment failure when demonstrating positive (detectable) results

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 6 - Non-detectable	207 Participants	105 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 10 - Missing	8 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 1 - Non-detectable	99 Participants	53 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 1 - Detectable	117 Participants	57 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 1 - Non-evaluable	1 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 1 - Missing	2 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 3 - Non-detectable	171 Participants	86 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 3 - Detectable	46 Participants	21 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 3 - Non-evaluable	0 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 3 - Missing	2 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 6 - Detectable	4 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 6 - Non-evaluable	3 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 6 - Missing	5 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 8 - Non-detectable	210 Participants	105 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 8 - Detectable	3 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 8 - Non-evaluable	2 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 8 - Missing	4 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 10 - Non-detectable	206 Participants	105 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 10 - Detectable	3 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 10 - Non-evaluable	2 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 11 - Non-detectable	205 Participants	102 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 11 - Detectable	3 Participants	5 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 11 - Non-evaluable	1 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results Visit 11 - Missing	10 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: up to 7 days after last application of study drug

TEAEs comprised events which first occurred or worsened at or after first application of study drug during the course of the study up to and including 7 days after last application of study drug

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any treatment-emergent adverse event (TEAE)	147 Participants	66 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any Serious TEAE	6 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1

TEAEs comprised events which first occurred or worsened at study start up to end of study in part 2. In Part 2, only AEs considered at least possibly related to nifurtimox (administered in part 1) and those caused by protocol-related procedures were reported.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=197 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=98 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 2 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any SAE related to protocol	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) AE with outcome death	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any AE	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any study drug-related AE	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any AE related to protocol	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any SAE	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 2 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any study drug-related SAE	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

The Number Analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Creatinine (mg/dL)	3 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Albumin (g/dL)	49 Participants	21 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Alkaline Phosphatase (U/L)	11 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Alanine Aminotransferase (U/L)	19 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Direct Bilirubin (mg/dL)	21 Participants	9 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Blood Urea Nitrogen (mg/dL)	11 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Protein (g/dL)	42 Participants	14 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Urate (mg/dL)	7 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Glucose (mg/dL)	15 Participants	13 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Aspartate Aminotransferase (U/L)	27 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment Bilirubin (mg/dL)	19 Participants	9 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Alkaline Phosphatase (U/L)	4 Participants	4 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Alanine Aminotransferase (U/L)	6 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Aspartate Aminotransferase (U/L)	1 Participants	5 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Direct Bilirubin (mg/dL)	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Blood Urea Nitrogen (mg/dL)	31 Participants	15 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Urate (mg/dL)	32 Participants	18 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Protein (g/dL)	17 Participants	15 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Creatinine (mg/dL)	22 Participants	10 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Albumin (g/dL)	14 Participants	4 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Bilirubin (mg/dL)	7 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment Glucose (mg/dL)	29 Participants	18 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

The number analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. Subjects with missing or high abnormal values at baseline are not included in the number analyzed. The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Hematocrit (%	19 Participants	8 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Hemoglobin (g/dL)	15 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Erythrocytes (T/L) in Blood	21 Participants	9 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Ery. Mean Corpuscular Volume (fL) in Blood	20 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Ery. Mean Corpuscular Hemoglobin (pg) in Blood	14 Participants	5 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Leukocytes (GIGA/L) in Blood	41 Participants	16 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Neutrophils/Leukocytes (%)	38 Participants	12 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Neutrophils (GIGA/L)	36 Participants	8 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Lymphocytes/Leukocytes (%)	35 Participants	17 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Lymphocytes (GIGA/L)	21 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Monocytes/Leukocytes (%)	33 Participants	17 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Monocytes (GIGA/L)	17 Participants	15 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Eosinophils/Leukocytes (%)	58 Participants	26 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Eosinophils (GIGA/L)	53 Participants	22 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Basophils/Leukocytes (%)	20 Participants	7 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Basophils (GIGA/L)	10 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Platelets (GIGA/L) in Blood	27 Participants	13 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment Ery. Mean Corpuscular HGB Conc. (g/dL) in Blood	23 Participants	6 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

The number analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. Subjects with missing or low abnormal values at baseline are not included in the number analyzed. The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Hematocrit (%	30 Participants	17 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Hemoglobin (g/dL)	23 Participants	17 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Erythrocytes (T/L) in Blood	15 Participants	9 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Ery. Mean Corpuscular Volume (fL) in Blood	16 Participants	6 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Ery. Mean Corpuscular Hemoglobin (pg) in Blood	19 Participants	10 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Ery. Mean Corpuscular HGB Conc. (g/dL) in Blood	29 Participants	21 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Leukocytes (GIGA/L) in Blood	39 Participants	18 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Neutrophils/Leukocytes (%)	53 Participants	27 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Neutrophils (GIGA/L)	46 Participants	25 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Lymphocytes/Leukocytes (%)	40 Participants	9 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Lymphocytes (GIGA/L)	5 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Monocytes/Leukocytes (%)	54 Participants	28 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Monocytes (GIGA/L)	33 Participants	22 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Eosinophils/Leukocytes (%)	13 Participants	5 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Eosinophils (GIGA/L)	14 Participants	5 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Basophils/Leukocytes (%)	1 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Basophils (GIGA/L)	1 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment Platelets (GIGA/L) in Blood	6 Participants	3 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

The Number Analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Treatment-emergent High Coagulation Abnormalities by Treatment Prothrombin Time (sec) in Plasma	38 Participants	23 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Coagulation Abnormalities by Treatment Activated Partial Thromboplastin	9 Participants	10 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent High Coagulation Abnormalities by Treatment Time in Plasma Prothrombin Intl. Normalized Ratio	21 Participants	13 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Treatment-emergent Low Coagulation Abnormalities by Treatment Prothrombin Time (sec) in Plasma	10 Participants	5 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Coagulation Abnormalities by Treatment Activated Partial Thromboplastin	15 Participants	2 Participants	—	—	—	—	—	—	—	—	—	—
Part 1 - Number of Subjects With Treatment-emergent Low Coagulation Abnormalities by Treatment Time in Plasma Prothrombin Intl. Normalized Ratio	14 Participants	5 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

Urinalysis was performed and the following parameters evaluated: bilirubin, blood (red blood cells, white blood cells), chorionic gonadotropin β, glucose, ketones, leukocytes, nitrite, pH, protein, specific gravity, and urobilinogen.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Abnormal Urinalysis Findings Considered as Clinically Significant or Reported as Adverse Events (AEs)	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

Clinical significance of abnormal ECG was based on the judgement of the investigator

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Number of Subjects With Abnormal ECG Findings Considered as Clinically Significant by Investigators	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and up to 420 days (Visit 11 post-treatment)

Systolic Blood Pressure

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 1	1.09 mmHg Standard Deviation 7.79 • Interval 7.79 to	0.69 mmHg Standard Deviation 7.85 • Interval 7.85 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 2	-3.75 mmHg Standard Deviation 7.50 • Interval 7.5 to	-5.00 mmHg Standard Deviation 7.07 • Interval 7.07 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 3	1.08 mmHg Standard Deviation 9.98 • Interval 9.98 to	-0.50 mmHg Standard Deviation 8.45 • Interval 8.45 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 6	-0.74 mmHg Standard Deviation 10.70 • Interval 10.7 to	-1.12 mmHg Standard Deviation 9.89 • Interval 9.89 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 8	-0.41 mmHg Standard Deviation 11.01 • Interval 11.01 to	0.48 mmHg Standard Deviation 11.24 • Interval 11.24 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 9	-0.13 mmHg Standard Deviation 11.11 • Interval 11.11 to	-0.45 mmHg Standard Deviation 10.49 • Interval 10.49 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 10	-0.02 mmHg Standard Deviation 10.46 • Interval 10.46 to	-1.48 mmHg Standard Deviation 10.95 • Interval 10.95 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 11	1.20 mmHg Standard Deviation 11.52 • Interval 11.52 to	1.57 mmHg Standard Deviation 10.70 • Interval 10.7 to	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and up to 420 days (Visit 11 post-treatment)

Diastolic Blood Pressure

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 2	-1.25 mmHg Standard Deviation 2.50 • Interval 2.5 to	-1.00 mmHg Standard Deviation 2.00 • Interval 2.0 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 3	0.76 mmHg Standard Deviation 8.36 • Interval 8.36 to	0.26 mmHg Standard Deviation 8.05 • Interval 8.05 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 1	1.00 mmHg Standard Deviation 7.72 • Interval 7.72 to	0.90 mmHg Standard Deviation 7.90 • Interval 7.9 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 6	0.26 mmHg Standard Deviation 10.87 • Interval 10.87 to	-0.14 mmHg Standard Deviation 10.21 • Interval 10.21 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 8	0.08 mmHg Standard Deviation 9.91 • Interval 9.91 to	0.93 mmHg Standard Deviation 10.17 • Interval 10.17 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 9	-0.68 mmHg Standard Deviation 8.81 • Interval 8.81 to	-0.21 mmHg Standard Deviation 10.03 • Interval 10.03 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 10	0.99 mmHg Standard Deviation 9.90 • Interval 9.9 to	0.85 mmHg Standard Deviation 9.53 • Interval 9.53 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline VISIT 11	2.30 mmHg Standard Deviation 11.06 • Interval 11.06 to	3.25 mmHg Standard Deviation 10.95 • Interval 10.95 to	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and up to 420 days (Visit 11 post-treatment)

Respiratory Rate

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline VISIT 1	0.12 BREATHS/MIN Standard Deviation 4.10 • Interval 4.1 to	0.47 BREATHS/MIN Standard Deviation 2.91 • Interval 2.91 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline VISIT 2	-1.50 BREATHS/MIN Standard Deviation 3.42 • Interval 3.42 to	-1.00 BREATHS/MIN Standard Deviation 1.15 • Interval 1.15 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline VISIT 3	-0.05 BREATHS/MIN Standard Deviation 3.15 • Interval 3.15 to	-0.14 BREATHS/MIN Standard Deviation 3.91 • Interval 3.91 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline VISIT 6	-0.57 BREATHS/MIN Standard Deviation 4.16 • Interval 4.16 to	-0.06 BREATHS/MIN Standard Deviation 3.87 • Interval 3.87 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline VISIT 8	-0.77 BREATHS/MIN Standard Deviation 4.04 • Interval 4.04 to	0.04 BREATHS/MIN Standard Deviation 4.58 • Interval 4.58 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline VISIT 9	-1.01 BREATHS/MIN Standard Deviation 4.06 • Interval 4.06 to	-0.50 BREATHS/MIN Standard Deviation 3.76 • Interval 3.76 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline VISIT 10	-1.36 BREATHS/MIN Standard Deviation 4.50 • Interval 4.5 to	-0.24 BREATHS/MIN Standard Deviation 3.60 • Interval 3.6 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline VISIT 11	-1.93 BREATHS/MIN Standard Deviation 5.10 • Interval 5.1 to	-0.74 BREATHS/MIN Standard Deviation 4.61 • Interval 4.61 to	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and up to 420 days (Visit 11 post-treatment)

Heart Rate

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline VISIT 1	-1.08 BEATS/MIN Standard Deviation 10.19 • Interval 10.19 to	0.26 BEATS/MIN Standard Deviation 11.37 • Interval 11.37 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline VISIT 2	-6.75 BEATS/MIN Standard Deviation 2.22 • Interval 2.22 to	-0.75 BEATS/MIN Standard Deviation 2.99 • Interval 2.99 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline VISIT 3	0.04 BEATS/MIN Standard Deviation 10.11 • Interval 10.11 to	-0.51 BEATS/MIN Standard Deviation 11.46 • Interval 11.46 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline VISIT 6	-0.78 BEATS/MIN Standard Deviation 11.49 • Interval 11.49 to	-0.75 BEATS/MIN Standard Deviation 11.92 • Interval 11.92 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline VISIT 8	-1.27 BEATS/MIN Standard Deviation 11.65 • Interval 11.65 to	-1.34 BEATS/MIN Standard Deviation 11.03 • Interval 11.03 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline VISIT 9	-1.26 BEATS/MIN Standard Deviation 11.97 • Interval 11.97 to	-1.63 BEATS/MIN Standard Deviation 10.56 • Interval 10.56 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline VISIT 10	-3.28 BEATS/MIN Standard Deviation 11.87 • Interval 11.87 to	-3.28 BEATS/MIN Standard Deviation 11.61 • Interval 11.61 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline VISIT 11	-3.57 BEATS/MIN Standard Deviation 12.57 • Interval 12.57 to	-4.66 BEATS/MIN Standard Deviation 14.73 • Interval 14.73 to	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and up to 420 days (Visit 11 post-treatment)

Temperature

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=111 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Mean Changes in Vital Signs (Body Temperature) Between the Treatment Groups From Baseline VISIT 1	0.01 °C Standard Deviation 0.39 • Interval 0.39 to	0.04 °C Standard Deviation 0.36 • Interval 0.36 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Body Temperature) Between the Treatment Groups From Baseline VISIT 2	-0.35 °C Standard Deviation 0.45 • Interval 0.45 to	-0.03 °C Standard Deviation 0.39 • Interval 0.39 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Body Temperature) Between the Treatment Groups From Baseline VISIT 3	-0.10 °C Standard Deviation 0.36 • Interval 0.36 to	0.04 °C Standard Deviation 0.43 • Interval 0.43 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Body Temperature) Between the Treatment Groups From Baseline VISIT 6	-0.06 °C Standard Deviation 0.44 • Interval 0.44 to	0 °C Standard Deviation 0.44 • Interval 0.44 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Body Temperature) Between the Treatment Groups From Baseline VISIT 8	-0.06 °C Standard Deviation 0.45 • Interval 0.45 to	0.05 °C Standard Deviation 0.42 • Interval 0.42 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Body Temperature) Between the Treatment Groups From Baseline VISIT 9	-0.03 °C Standard Deviation 0.44 • Interval 0.44 to	0.02 °C Standard Deviation 0.47 • Interval 0.47 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Body Temperature) Between the Treatment Groups From Baseline VISIT 10	-0.07 °C Standard Deviation 0.49 • Interval 0.49 to	-0.01 °C Standard Deviation 0.52 • Interval 0.52 to	—	—	—	—	—	—	—	—	—	—
Part 1 - Mean Changes in Vital Signs (Body Temperature) Between the Treatment Groups From Baseline VISIT 11	-0.14 °C Standard Deviation 0.51 • Interval 0.51 to	-0.10 °C Standard Deviation 0.50 • Interval 0.5 to	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

This exploratory efficacy analysis evaluated the cure rate assessed as seroconversion of nifurtimox after 1-year post-treatment follow-up with that of published data for benznidazole (Sosa Estani et al. 1998 and de Andrade et al. 1996) at 4- and 3-year post-treatment follow-up, respectively, used as historical control.

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1: Number of Participants Cured With 60-day Regimen Compared With Historical Active Control (Benznidazole)	10 Participants	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

Using frequencies of matches and mismatches to assess agreement Reactive = Reac ELISA Detectable = Detec qPCR Non-reactive = Nonreac ELISA Non-detectable = Nondetec qPCR Non evaluable = Noneval qPCR qPCR Missing = Miss qPCR Missing conventional testing = Miss ELISA

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=219 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable n=219 Participants Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable n=219 Participants Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable n=219 Participants Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing n=219 Participants Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable n=111 Participants Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable n=111 Participants Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable n=111 Participants Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable n=111 Participants Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable n=111 Participants Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable n=111 Participants Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and qPCR Testing by Visit Visit 11	3 Participants	194 Participants	0 Participants	11 Participants	1 Participants	1 Participants	5 Participants	96 Participants	0 Participants	6 Participants	1 Participants	0 Participants
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and qPCR Testing by Visit Visit 1	117 Participants	99 Participants	0 Participants	0 Participants	1 Participants	2 Participants	57 Participants	52 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and qPCR Testing by Visit Visit 8	3 Participants	210 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	103 Participants	0 Participants	1 Participants	2 Participants	1 Participants
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and qPCR Testing by Visit Visit 10	3 Participants	195 Participants	0 Participants	11 Participants	2 Participants	0 Participants	2 Participants	99 Participants	0 Participants	6 Participants	2 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

Using frequencies of matches and mismatches to assess agreement Reactive = Reac ELISA Reactive = Reac F29 Non-reactive = Nonreac ELISA Non-reactive = Nonreac F29

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=219 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable n=219 Participants Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable n=219 Participants Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable n=111 Participants Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing n=111 Participants Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable n=111 Participants Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable n=111 Participants Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 3	133 Participants	85 Participants	0 Participants	0 Participants	64 Participants	43 Participants	0 Participants	1 Participants	—	—	—	—
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 1	142 Participants	77 Participants	0 Participants	0 Participants	72 Participants	38 Participants	0 Participants	1 Participants	—	—	—	—
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 6	131 Participants	83 Participants	0 Participants	0 Participants	67 Participants	42 Participants	0 Participants	1 Participants	—	—	—	—
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 8	124 Participants	91 Participants	0 Participants	63 Participants	63 Participants	43 Participants	0 Participants	1 Participants	—	—	—	—
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 10	108 Participants	92 Participants	2 Participants	9 Participants	61 Participants	42 Participants	0 Participants	6 Participants	—	—	—	—
Part 1 - Relationship of Conventional Serology (Total Purified Antigen ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 11	93 Participants	106 Participants	3 Participants	8 Participants	54 Participants	48 Participants	0 Participants	6 Participants	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

Using frequencies of matches and mismatches to assess agreement Reactive = Reac ELISA Reactive = Reac F29 Non-reactive = Nonreac ELISA Non-reactive= Nonreac F29

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=219 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=219 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable n=219 Participants Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable n=219 Participants Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable n=111 Participants Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing n=111 Participants Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable n=111 Participants Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Relationship of Conventional Serology (Recombinant ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 11	93 Participants	106 Participants	3 Participants	0 Participants	53 Participants	1 Participants	6 Participants	—	—	—	—	—
Part 1 - Relationship of Conventional Serology (Recombinant ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 1	142 Participants	77 Participants	0 Participants	0 Participants	72 Participants	0 Participants	1 Participants	—	—	—	—	—
Part 1 - Relationship of Conventional Serology (Recombinant ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 3	133 Participants	85 Participants	0 Participants	0 Participants	64 Participants	0 Participants	1 Participants	—	—	—	—	—
Part 1 - Relationship of Conventional Serology (Recombinant ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 6	131 Participants	81 Participants	0 Participants	2 Participants	67 Participants	0 Participants	1 Participants	—	—	—	—	—
Part 1 - Relationship of Conventional Serology (Recombinant ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 8	124 Participants	90 Participants	0 Participants	1 Participants	63 Participants	0 Participants	1 Participants	—	—	—	—	—
Part 1 - Relationship of Conventional Serology (Recombinant ELISA) and Non-conventional (ELISA-F29) Serologic Testing by Visit Visit 10	108 Participants	91 Participants	2 Participants	10 Participants	59 Participants	2 Participants	5 Participants	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

Sero-reduction is defined as a =\> 20% reduction in optical density \[OD\]) using two conventional ELISA serology tests in subjects =\> 8 months to \< 18 years of age at randomization; Others: reactive results that are not sero-reduction in subjects =\> 8 months to \< 18 years of age at randomization; or reactive results in subjects \< 8 months of age at randomization. Non-reactive ELISA = Nonreac ELISA Non-reactive IHA = Nonreac IHA Reactive IHA decrease = Reac IHA dec React IHA nochange = Reac IHA nochange Reactive ELISA: seroreduction = Reac ELISA reduc Reactive ELISA: others = Reac ELISA other

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=318 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=318 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable n=318 Participants Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable n=318 Participants Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable n=318 Participants Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing n=330 Participants Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable n=318 Participants Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable n=318 Participants Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable n=318 Participants Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable n=318 Participants Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Relationship of Conventional Serology (ELISA) to Indirect Hemagglutination Assay (IHA) Results Nifurtimox 60 days	8 Participants	2 Participants	0 Participants	2 Participants	40 Participants	20 Participants	1 Participants	47 Participants	89 Participants	1 Participants	—	—
Part 1 - Relationship of Conventional Serology (ELISA) to Indirect Hemagglutination Assay (IHA) Results Nifurtimox 30 days	4 Participants	1 Participants	0 Participants	0 Participants	12 Participants	4 Participants	1 Participants	30 Participants	58 Participants	0 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 420 days (Visit 11 post-treatment)

Cure is defined as sero-reduction (in subjects =\> 8 months to \< 18 years of age at randomization) or sero-conversion (in all subjects). Sero-reduction is defined as a =\> 20% reduction in optical density \[OD\]) measured by two conventional ELISA serology tests and sero-conversion is defined as negative Immunoglobulin G \[IgG\] concentration measured by two conventional ELISA serology tests. Cure = Cure Non reactive/reactive decreasing = Nonreac/reac dec Reactive non-decreasing = Reac nondec No cure = No Cure Missing IHA testing = IHA missing

Outcome measures

Outcome measures
Measure	Nifurtimox 60 Days / Arm 1 n=318 Participants Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)	Nifurtimox 30 Days, Then Placebo 30 Days / Arm 2 n=318 Participants Nifurtimox tablets administered three times daily for 30 days, followed by placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)	Nifurtimox 60 Days Non-reactive Detectable n=318 Participants Nifurtimox 60 days with Nonreac ELISA and Detec qPCR	Nifurtimox 60 Days Non-reactive Non-detectable n=318 Participants Nifurtimox 60 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 60 Days Reactive Non Evaluable n=318 Participants Nifurtimox 60 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 60 Days Reactive qPCR Missing Nifurtimox 60 days with Reac ELISA and missing qPCR	Nifurtimox 30 Days Reactive Detectable Nifurtimox 30 days with Reac ELISA and Detec qPCR	Nifurtimox 30 Days Reactive Non-detectable Nifurtimox 30 days with Reac ELISA and Nondetec qPCR	Nifurtimox 30 Days Non-reactive Detectable Nifurtimox 30 days with Nonreac ELISA and Detec qPCR	Nifurtimox 30 Days Non-reactive Non-detectable Nifurtimox 30 days with Nonreac ELISA and Nondetec qPCR	Nifurtimox 30 Days Reactive Non Evaluable Nifurtimox 30 days with Reac ELISA and Non evaluable qPCR	Nifurtimox 30 Days Missing Conventional Testing Non-detectable Nifurtimox 30 days with Miss ELISA and Nondetec qPCR
Part 1 - Relationship Between Conventional ELISA Results in Terms of Cure or No Cure and IHA Results in All Patients Nifurtimox 60 days	52 Participants	20 Participants	48 Participants	89 Participants	1 Participants	—	—	—	—	—	—	—
Part 1 - Relationship Between Conventional ELISA Results in Terms of Cure or No Cure and IHA Results in All Patients Nifurtimox 30 days	17 Participants	4 Participants	29 Participants	58 Participants	0 Participants	—	—	—	—	—	—	—

Adverse Events

Nifurtimox 60-day Regimen

Serious events: 6 serious events

Other events: 128 other events

Deaths: 0 deaths

Nifurtimox 30-day Regimen

Serious events: 3 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Nifurtimox 60-day Regimen n=219 participants at risk Nifurtimox daily dose 8-10 mg/kg (adolescents, 40-60 kg) or 10-20 mg/kg (infants/children, below 40 kg) for 60 days	Nifurtimox 30-day Regimen n=111 participants at risk Nifurtimox daily dose 8-10 mg/kg (adolescents, 40-60 kg) or 10-20 mg/kg (infants/children, below 40 kg) for 30 days followed by placebo
Gastrointestinal disorders Abdominal pain	8.7% 19/219 • Number of events 27 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	8.1% 9/111 • Number of events 11 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Gastrointestinal disorders Abdominal pain upper	6.8% 15/219 • Number of events 20 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	3.6% 4/111 • Number of events 5 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Gastrointestinal disorders Diarrhoea	7.3% 16/219 • Number of events 17 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	5.4% 6/111 • Number of events 7 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Gastrointestinal disorders Nausea	8.7% 19/219 • Number of events 24 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	12.6% 14/111 • Number of events 15 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Gastrointestinal disorders Vomiting	15.1% 33/219 • Number of events 57 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	9.0% 10/111 • Number of events 11 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
General disorders Pyrexia	9.1% 20/219 • Number of events 25 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	3.6% 4/111 • Number of events 5 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Infections and infestations Bronchitis	5.5% 12/219 • Number of events 14 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	5.4% 6/111 • Number of events 7 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Infections and infestations Nasopharyngitis	10.0% 22/219 • Number of events 28 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	9.9% 11/111 • Number of events 13 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Infections and infestations Pharyngitis	5.9% 13/219 • Number of events 13 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.90% 1/111 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Infections and infestations Upper respiratory tract infection	5.9% 13/219 • Number of events 17 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.90% 1/111 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Metabolism and nutrition disorders Decreased appetite	11.4% 25/219 • Number of events 27 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	7.2% 8/111 • Number of events 8 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Nervous system disorders Headache	13.7% 30/219 • Number of events 44 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	14.4% 16/111 • Number of events 23 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.

Additional Information

Therapeutic Area Head

Bayer AG

Phone: 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Nifurtimox 60-day Regimen n=219 participants at risk Nifurtimox daily dose 8-10 mg/kg (adolescents, 40-60 kg) or 10-20 mg/kg (infants/children, below 40 kg) for 60 days	Nifurtimox 30-day Regimen n=111 participants at risk Nifurtimox daily dose 8-10 mg/kg (adolescents, 40-60 kg) or 10-20 mg/kg (infants/children, below 40 kg) for 30 days followed by placebo
Infections and infestations Cellulitis	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Infections and infestations Chronic tonsillitis	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Infections and infestations Ear infection	0.00% 0/219 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.90% 1/111 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Infections and infestations Gastroenteritis	0.00% 0/219 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.90% 1/111 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Infections and infestations Pelvic inflammatory disease	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Infections and infestations Pneumonia	0.00% 0/219 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.90% 1/111 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Injury, poisoning and procedural complications Burns second degree	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Injury, poisoning and procedural complications Snake bite	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Injury, poisoning and procedural complications Upper limb fracture	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Nervous system disorders Febrile convulsion	0.00% 0/219 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.90% 1/111 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Nervous system disorders Seizure	0.91% 2/219 • Number of events 3 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Nervous system disorders Syncope	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Psychiatric disorders Completed suicide	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Respiratory, thoracic and mediastinal disorders Apnoea	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Skin and subcutaneous tissue disorders Urticaria	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.00% 0/111 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Surgical and medical procedures Abortion induced	0.00% 0/219 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.90% 1/111 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.
Gastrointestinal disorders Abdominal pain	0.46% 1/219 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.	0.90% 1/111 • Number of events 1 • Part 1: From first application of study drug up to and including 7 days after last application of study drug Part 2: first occurred or worsened at start of study part 2 up to 3 years.