Trial Outcomes & Findings for Fexinidazole in Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage (NCT NCT03025789)

Results Overview

Treatment outcome at Month 18 is categorized as success or failure. Success is defined as a cure, according to the criteria adapted from the World Health Organization (WHO) update of the methodological framework for clinical trials in Sept 2014 (WHO/HTM/NTD/IDM/2015.5). Failure is defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the Month 18 visit, an unfavorable outcome earlier than Month 18, or signs and symptoms evoking a relapse at Month 18. Success rate at Month 18 is defined as the percentage of participants (regardless of g-HAT stage) whose treatment outcome is a success at Month 18. An estimate of the success rate at Month 18 and the 95% exact Clopper-Pearson confidence interval (CI) of the estimate are provided.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

174 participants

Primary outcome timeframe

Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)

Results posted on

2025-01-08

Participant Flow

The study was conducted at 8 centers in the Democratic Republic of Congo and 1 center in Guinea. 200 participants were screened and signed informed consent. 3 patients had no trypanosomes in their blood and were not included since g-HAT positivity could not be confirmed. Of the 197 screened HAT-positive participants, 174 were included and treated, and 23 were not included, mainly due to inclusion/exclusion criteria not met. Participants were enrolled between 10 November 2016 and 10 August 2019.

The pre-treatment period of up to 15 days included screening and treatment of concurrent malaria/soil-transmitted helminthiasis. At the end of this period, all participants (regardless of g-HAT stage and treatment setting) were treated with fexinidazole.

Participant milestones

Participant milestones
Measure	Inpatients Participants received fexinidazole orally for 10 days as inpatients (at the hospital) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Overall Study STARTED	136	38
Overall Study COMPLETED	129	35
Overall Study NOT COMPLETED	7	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Inpatients Participants received fexinidazole orally for 10 days as inpatients (at the hospital) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Overall Study Lack of Efficacy	6	1
Overall Study Death	1	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Fexinidazole in Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inpatients n=136 Participants Participants received fexinidazole orally for 10 days as inpatients (at the hospital) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Total n=174 Participants Total of all reporting groups
Age, Continuous	26.0 years STANDARD_DEVIATION 15.5 • n=5 Participants	27.9 years STANDARD_DEVIATION 18.0 • n=7 Participants	26.4 years STANDARD_DEVIATION 16.0 • n=5 Participants
Sex: Female, Male Female	78 Participants n=5 Participants	18 Participants n=7 Participants	96 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	20 Participants n=7 Participants	78 Participants n=5 Participants
Race/Ethnicity, Customized Sub-Saharan African	136 Participants n=5 Participants	38 Participants n=7 Participants	174 Participants n=5 Participants
Region of Enrollment Guinea	26 Participants n=5 Participants	6 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment Congo, The Democratic Republic of the	110 Participants n=5 Participants	32 Participants n=7 Participants	142 Participants n=5 Participants
g-HAT stage: Stage 1/intermediate, Stage 2 Stage 1/intermediate	53 Participants n=5 Participants	17 Participants n=7 Participants	70 Participants n=5 Participants
g-HAT stage: Stage 1/intermediate, Stage 2 Stage 2	83 Participants n=5 Participants	21 Participants n=7 Participants	104 Participants n=5 Participants
White blood cell (WBC) in cerebrospinal fluid (CSF) 100 cells/µL or lower	80 Participants n=5 Participants	20 Participants n=7 Participants	100 Participants n=5 Participants
White blood cell (WBC) in cerebrospinal fluid (CSF) Higher than 100 cells/µL	56 Participants n=5 Participants	18 Participants n=7 Participants	74 Participants n=5 Participants

PRIMARY outcome

Timeframe: Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)

Population: This population includes all patients in the mITT population (i.e. who received at least one table of fexinidazole), regardless of treatment setting (inpatients and outpatients). The efficacy of fexinidazole was not meant to be studied in inpatients and outpatients separately.

Treatment outcome at Month 18 is categorized as success or failure. Success is defined as a cure, according to the criteria adapted from the World Health Organization (WHO) update of the methodological framework for clinical trials in Sept 2014 (WHO/HTM/NTD/IDM/2015.5). Failure is defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the Month 18 visit, an unfavorable outcome earlier than Month 18, or signs and symptoms evoking a relapse at Month 18. Success rate at Month 18 is defined as the percentage of participants (regardless of g-HAT stage) whose treatment outcome is a success at Month 18. An estimate of the success rate at Month 18 and the 95% exact Clopper-Pearson confidence interval (CI) of the estimate are provided.

Outcome measures

Outcome measures
Measure	Outpatients n=174 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Percentage of Participants Whose Treatment Outcome at Month 18 is a Success	93.1 percentage of participants Interval 88.3 to 96.4	—

SECONDARY outcome

Timeframe: Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)

Population: This population includes all patients in the mITT population (i.e. who received at least one table of fexinidazole), regardless of treatment setting (inpatients and outpatients). The efficacy of fexinidazole was not meant to be studied in inpatients and outpatients separately.

Treatment outcome at Month 12 is categorized as success or failure. Success is defined as a cure, according to the criteria adapted from the World Health Organization (WHO) update of the methodological framework for clinical trials in Sept 2014 (WHO/HTM/NTD/IDM/2015.5). Failure is defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the Month 12 visit, an unfavorable outcome earlier than Month 12, or signs and symptoms evoking a relapse at Month 12 (data collected at Month 18 are considered, if available). Success rate at Month 12 is defined as the percentage of participants (regardless of g-HAT stage) whose treatment outcome is a success at Month 12. An estimate of the success rate at Month 12 and the 95% exact Clopper-Pearson confidence interval (CI) of the estimate are provided.

Outcome measures

Outcome measures
Measure	Outpatients n=174 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Percentage of Participants Whose Treatment Outcome at Month 12 is a Success	94.3 percentage of participants Interval 89.7 to 97.2	—

SECONDARY outcome

Timeframe: Between the first intake of fexinidazole (Day 1) and the end of the observation period, or the end of the follow-up period (18 months) for non-serious AEs assessed as related to fexinidazole

Population: The mITT population included all participants who received at least one table of fexinidazole.

AE severity is graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for AEs (CTCAE), Version 4.03 and, for certain laboratory parameters, modified CTCAE is used. Grade ≥3 AEs include the following events: Grade 3 events (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living), Grade 4 events (life-threatening consequences; urgent intervention indicated), and Grade 5 events (death related to AE). The observation period extends from the first intake of fexinidazole (Day 1) until the end-of-hospitalization visit (between Day 13 and Day 18) for inpatients and until the end-of-treatment visit (on Day 11) for outpatients.

Outcome measures

Outcome measures
Measure	Outpatients n=136 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Participants With Any Grade ≥ 3 Treatment-emergent Adverse Events (AEs) Including Laboratory and Hematological Abnormalities (if Considered Clinically Significant)	10 Participants	4 Participants

SECONDARY outcome

Timeframe: Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)

Population: The mITT population included all participants who received at least one table of fexinidazole.

An SAE was defined as any AE that: resulted in death; was life-threatening; required inpatient hospitalisation or prolongation of existing hospitalisation; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was an important medical event that was not immediately life-threatening or did not result in death, but that jeopardised the patient's safety or required an intervention to prevent one of the outcomes above. Patients treated on an outpatient basis who required hospitalisation, for whatever reason, underwent the same procedures as patients initially treated in hospital, up to the end of the hospitalisation period. During this period, and up to Day 13 or Day 18, the reasons for hospitalisation were not to be considered to be SAEs solely based on the criterion of hospitalisation, but could be considered to be SAEs based on other criteria.

Outcome measures

Outcome measures
Measure	Outpatients n=136 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE)	10 Participants	4 Participants

SECONDARY outcome

Timeframe: Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)

Population: The mITT population included all participants who received at least one table of fexinidazole.

Number of patients who prematurely discontinued treatment (temporarily or permanently) for reasons related to safety (including overdose).

Outcome measures

Outcome measures
Measure	Outpatients n=136 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Participants With Any Temporary or Permanent Treatment Discontinuation (Inpatient or Outpatient) for Reasons Related to Safety	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)

Population: All outpatients included in the mITT population (i.e. who received at least one table of fexinidazole). This outcome measure is only applicable to outpatients to investigate the proportion of outpatients who had to be hospitalized during treatment due to safety.

Number of outpatients who are hospitalized for reasons related to safety (including overdose). An outpatient is considered as "hospitalized for reasons related to safety" if he/she is initially planned to be treated as an outpatient but experiences an AE during the treatment period (Day 1 to Day 10) and is hospitalized during the treatment period.

Outcome measures

Outcome measures
Measure	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Participants With Any Hospitalization for Reasons Related to Safety (Outpatients Only)	2 Participants	—

SECONDARY outcome

Timeframe: Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)

Population: The mITT population included all participants who received at least one table of fexinidazole.

Number of patients who prematurely discontinued treatment permanently for reasons related to safety (including overdose).

Outcome measures

Outcome measures
Measure	Outpatients n=136 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Participants With Any Permanent Treatment Discontinuation (Inpatient or Outpatient) for Reasons Related to Safety	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)

Population: All outpatients included in the mITT population (i.e. participants who received at least one tablet of fexinidazole).

Number of outpatients who completed the full course of the 10-day treatment. Full completion can be either completing the 10-day treatment in the outpatient setting, or starting treatment as an outpatient but finishing treatment at the hospital, for those who have to be hospitalized (for any reason). At Day 11, the participant and/or caregiver have to present the treatment packaging they received at study inclusion, and the investigator has to record if the treatment calendar was fully completed or not.

Outcome measures

Outcome measures
Measure	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Outpatients Who Were Compliant With the Full Course of the 10-day Treatment	38 Participants	—

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11)

Population: Three of the 38 outpatients included in the mITT population were hospitalized and completed treatment at the hospital. As a consequence, they did not fill out the compliance questionnaire designed for outpatients after treatment. Therefore, the total number of patients analyzed was 35 outpatients.

Number of patients whose response to the question "How did you take your treatment?" is correct, as determined by the study personnel leading the compliance interview at Day 11 (end-of-treatment visit). The expected answer for participants weighing 35 kg or more is: 2 phases. Day 1 to 4 = 3 tablets. Day 5 to 10 = 2 tablets. Tablets to be taken all at once during a meal. The expected answer for participants weighing less than 35 kg is: 2 phases. Day 1 to 4 = 2 tablets. Day 5 to 10 = 1 tablet. Tablets to be taken all at once during a meal. The answer is considered correct if the 4 key messages have been understood (treatment period composed of 2 phases, each with a different number of tablets to be taken; treatment to be taken for 10 days without interruption; tablets to be taken all at once every day; treatment to be taken during a meal)

Outcome measures

Outcome measures
Measure	Outpatients n=35 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Outpatients Who Were Compliant With the 10-day Treatment Posology, Including Taking the Correct Number of Tablets During the 2 Phases of Treatment and Taking Tablets All at Once Every Day, With Food and Without Any Interruption of Treatment	35 Participants	—

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11)

Population: All outpatients included in the mITT population (i.e. who received at least one table of fexinidazole).

The occurrence of temporary treatment discontinuation is recorded at Day 11 (end-of-treatment visit) in the case report form by the study personnel (Section on feasibility, question "Was the treatment temporarily discontinued?). Occurrence is presented as the number of outpatients who temporarily discontinued their treatment.

Outcome measures

Outcome measures
Measure	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Feasibility of Self-management of Treatment Intake in Outpatients: Occurrence of Temporary Treatment Discontinuation	0 Participants	—

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11)

Population: All outpatients included in the mITT population (i.e. who received at least one table of fexinidazole).

The occurrence of permanent treatment discontinuation is recorded at Day 11 (end-of-treatment visit) in the case report form by the study personnel (Section on feasibility, question "Was the treatment stopped permanently?). Occurrence is presented as the number of outpatients who prematurely (prior to Day 10) discontinued their treatment permanently.

Outcome measures

Outcome measures
Measure	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Feasibility of Self-management of Treatment Intake in Outpatients: Occurrence of Permanent Treatment Discontinuation	0 Participants	—

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11)

Population: All outpatients included in the mITT population (i.e. who received at least one table of fexinidazole).

The occurrence of delayed treatment start is recorded at Day 11 (end-of-treatment visit) in the case report form by the study personnel (Section on feasibility, date of first administration \[Day 1\] minus date of dispensing \[Day 0\] \> 1 day). The occurrence of delayed treatment start is presented as the number of outpatients who had their planned treatment start delayed by at least 1 day.

Outcome measures

Outcome measures
Measure	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Feasibility of Self-management of Treatment Intake in Outpatients: Delayed Treatment Start	0 Participants	—

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11)

Population: All outpatients included in the mITT population (i.e. who received at least one table of fexinidazole).

The occurrence of hospitalization is recorded at Day 11 (end-of-treatment visit) in the case report form by the study personnel (Section on feasibility, question "Did the patient finish his/her treatment in hospital?"), with "non-compliance" as the reason for hospitalization. Occurrence of hospitalization is presented as the number of outpatients who had to be hospitalized during the treatment period due to non-compliance.

Outcome measures

Outcome measures
Measure	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Feasibility of Self-management of Treatment Intake in Outpatients: Hospitalization During the Treatment Period Due to Non-compliance	1 Participants	—

SECONDARY outcome

Timeframe: Before treatment (Day 0)

Population: All outpatients included in the mITT population (i.e. who received at least one table of fexinidazole).

Full understanding of the instructions concerning the dosing regimen of fexinidazole is assessed at Day 0 (day of treatment dispensing) by the study personnel. During the interview, the study personnel ask the participant and/or caregiver 8 questions about posology. To each of these 8 questions, the study personnel tick 'Yes' if the immediate answer is consistent with the expected answer. Full understanding of the instructions requires all 8 questions to be answered correctly. Full understanding is presented as the number of patients who correctly answered all 8 questions.

Outcome measures

Outcome measures
Measure	Outpatients n=38 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Acceptability of Packaging in Outpatients: Full Understanding of Instructions Concerning Dosing Regimen	30 Participants	—

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11)

Population: Three of the 38 outpatients included in the mITT population were hospitalized and completed treatment at the hospital. As a consequence, they did not fill out the compliance questionnaire designed for outpatients after treatment. Therefore, the total number of patients analyzed was 35 outpatients.

Acceptability of packaging is assessed at Day 11 (end-of-treatment visit) by a questionnaire filled out by the participant and/or caregiver. The occurrence of help needed is presented as the number of outpatients who indicate at the end of treatment that they had to request help to follow the treatment (Section on acceptability, question "Did you have to request help to follow the treatment?").

Outcome measures

Outcome measures
Measure	Outpatients n=35 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Acceptability of Packaging in Outpatients: Help Requested to Follow the Treatment	10 Participants	—

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11)

Population: Three of the 38 outpatients included in the mITT population were hospitalized and completed treatment at the hospital. As a consequence, they did not fill out the compliance questionnaire designed for outpatients after treatment. Therefore, the total number of patients analyzed was 35 outpatients.

Acceptability of packaging is assessed at Day 11 (end-of-treatment visit) by a questionnaire filled out by the participant and/or caregiver. The number of patients who found the instructions helpful is recorded (Section on acceptability, question "Did you find the instruction sheet provided with the medication helpful / Did it help you to remember the important information?").

Outcome measures

Outcome measures
Measure	Outpatients n=35 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Acceptability of Packaging in Outpatients: Instructions Found Helpful	35 Participants	—

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11, 24 hours after last treatment administration)

Population: The PK population included all participants who received at least one table of fexinidazole and who had available PK data. The number of outpatients/inpatients in the PK analysis (36/138) differs from the main analysis (38/136) because 2 outpatients were hospitalized (on Day 3 and 5) and were considered as inpatients for the PK analysis (the outpatient hospitalized on Day 8 was considered as an outpatient for the PK analysis). Data were missing for 14 patients (10 inpatients and 4 outpatients).

Concentrations of fexinidazole is determined using a validated analytical method, in all patients with available PK data.

Outcome measures

Outcome measures
Measure	Outpatients n=128 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients n=32 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Whole Blood Concentration of Fexinidazole From Dry Blood Spot, Measured 24 Hours After the Last Dose of Fexinidazole	0.048 µg/mL Interval 0.01 to 0.27	0.054 µg/mL Interval 0.01 to 0.18

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11, 24 hours after last treatment administration)

Population: The PK population included all participants who received at least one table of fexinidazole and who had available PK data. The number of outpatients/inpatients in the PK analysis (36/138) differs from the main analysis (38/136) because 2 outpatients were hospitalized (on Day 3 and 5) and were considered as inpatients for the PK analysis (the outpatient hospitalized on Day 8 was considered as an outpatient for the PK analysis). Data were missing for 1 patient (1 outpatient).

Concentrations of fexinidazole metabolite M1 (fexinidazole sulfoxide) is determined using a validated analytical method, in all patients with available PK data.

Outcome measures

Outcome measures
Measure	Outpatients n=138 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients n=35 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Whole Blood Concentration of Fexinidazole Metabolite M1 From Dry Blood Spot, Measured 24 Hours After the Last Dose of Fexinidazole	1.928 µg/mL Interval 0.11 to 7.5	2.316 µg/mL Interval 0.13 to 4.41

SECONDARY outcome

Timeframe: End-of-treatment visit (Day 11, 24 hours after last treatment administration)

Population: The PK population included all participants who received at least one table of fexinidazole and who had available PK data. The number of outpatients/inpatients in the PK analysis (36/138) differs from the main analysis (38/136) because 2 outpatients were hospitalized (on Day 3 and 5) and were considered as inpatients for the PK analysis (the outpatient hospitalized on Day 8 was considered as an outpatient for the PK analysis). Data were missing for 1 patient (1 outpatient).

Concentrations of fexinidazole metabolite M2 (fexinidazole sulfone) is determined using a validated analytical method, in all patients with available PK data.

Outcome measures

Outcome measures
Measure	Outpatients n=138 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients n=35 Participants Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Whole Blood Concentration of Fexinidazole Metabolite M2 From Dry Blood Spot, Measured 24 Hours After the Last Dose of Fexinidazole	11.014 µg/mL Interval 3.54 to 33.3	11.725 µg/mL Interval 2.55 to 35.86

Adverse Events

Inpatients

Serious events: 10 serious events

Other events: 73 other events

Deaths: 1 deaths

Outpatients

Serious events: 4 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Inpatients n=136 participants at risk Participants received fexinidazole orally for 10 days as inpatients (at the hospital) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)	Outpatients n=38 participants at risk Participants received fexinidazole orally for 10 days as outpatients (at home) Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Infections and infestations Appendicitis	0.00% 0/136 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	2.6% 1/38 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Infections and infestations Cholera	0.00% 0/136 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	2.6% 1/38 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Infections and infestations Malaria	1.5% 2/136 • Number of events 2 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	2.6% 1/38 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Infections and infestations Tuberculous pleurisy	0.74% 1/136 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Injury, poisoning and procedural complications Uterine rupture	0.74% 1/136 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Metabolism and nutrition disorders Starvation	0.74% 1/136 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Nervous system disorders Epilepsy	1.5% 2/136 • Number of events 2 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Nervous system disorders Psychomotor hyperactivity	0.74% 1/136 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Nervous system disorders Psychomotor skills impaired	0.74% 1/136 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Pregnancy, puerperium and perinatal conditions Stillbirth	0.74% 1/136 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Pregnancy, puerperium and perinatal conditions Transverse presentation	0.74% 1/136 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Psychiatric disorders Anxiety	0.74% 1/136 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Psychiatric disorders Confusional state	0.00% 0/136 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	2.6% 1/38 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.
Psychiatric disorders Psychotic disorder due to a general medical condition	0.74% 1/136 • Number of events 1 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.	0.00% 0/38 • Per protocol, non-serious adverse events (AEs) were recorded as follows: for inpatients, from the first intake of fexinidazole (Day 1) until the end-of-hospitalization Visit (Day 13-18) and in outpatients, from the first intake of fexinidazole (Day 1) until the end-of-treatment Visit (Day 11). Treatment-emergent serious AEs were collected from the first intake of fexinidazole (Day 1) until the end of the follow-up (Month 18). The population of analysis corresponds to the mITT population. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs. Furthermore, any suspected transmission of an infectious agent via the Investigational Medicinal Product was also considered as an SAE.

Other adverse events

Additional Information

Dr. Olaf Valverde Mordt

Drugs for Neglected Diseases initiative (DNDi)

Phone: +41795431713

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor authorizes publications by a single site provided that multicentric results are published beforehand and that any communication is submitted to sponsor for review at least 28 days ahead of the expected date of publication. The sponsor can submit comments for a period of 28 days. Upon sponsor request, any confidential information will have to be removed from the communication before publishing.
Publication restrictions are in place

Restriction type: OTHER