Sleeping Sickness, Trypanosoma Brucei Gambiense; Infection, Trypanosomiasis, African
Conditions
Keywords
Human African Trypanosomiasis, Trypanosoma Brucei Gambiense, Sleeping sickness, g-HAT, g-HAT seropositive individuals
Brief summary
Human African trypanosomiasis (HAT) or sleeping sickness is a tropical disease which is endemic in sub-Saharan Africa. Most cases of HAT are due to the parasite Trypanosoma brucei gambiense (T.b. gambiense), which is transmitted by the bite of the tsetse fly. HAT can be fatal without diagnosis and treatment. Several treatment options are currently available to treat HAT caused by the T.b. gambiense parasite (g-HAT), but these treatments can be administered only after demonstrating via microscopy the presence of the parasite in a body fluid. However, there are factors such as low parasitaemia and the complexity and low sensitivity of parasitological methods that make such demonstration difficult. It has been demonstrated that a variable proportion (mainly depending on the prevalence) of such g-HAT sero-suspects are confirmed cases and, therefore, remain potential reservoirs of the parasite and a source of new infections hindering the efforts to eliminate the disease. The drug acoziborole was evaluated in a study called DNDi-OXA-02-HAT. During this study, patients with g-HAT from the DRC and Guinea took a single dose of acoziborole. This study showed that acoziborole has a high efficacy and is safe for treating patients with confirmed g-HAT . The present study is called DNDi-OXA-04-HAT. It included seropositive participants from the DRC and Guinea who did not have parasites detected via microscopy in a body fluid. Its objective was to collect data on the safety and tolerability of a single dose of acoziborole compared to a placebo (i.e. a dummy treatment). The results of this study would help decide if acoziborole can be used in the population of g-HAT seropositive individuals and help eliminate the HAT disease.
Detailed description
HAT, or sleeping sickness, is a neglected tropical disease which is endemic in sub Saharan Africa. This vector-borne parasitic disease is transmitted by the bite of the tsetse fly and can be fatal without diagnosis and treatment. The parasites responsible for HAT are the protozoa T.b. gambiense and T.b. rhodesiense. In 2021-2022, HAT due to T.b. gambiense (g-HAT) represented 94% of all HAT cases detected. Between 2018 and 2022, approximately 1.5 million people lived in areas (mainly rural areas of sub-Saharan Africa) considered to be at moderate to very high risk of HAT and where the disease is still considered as a public health problem. Thanks to efforts from national control programs, supported by the World Health Organization (WHO), non-governmental organizations, bilateral cooperations, the private sector (including pharmaceutical companies) and philanthropic organizations, the number of cases of g-HAT is consistently falling. With respectively 799 and 675 cases of g-HAT reported in 2022 and 2023, the global goal of sustainable disease elimination by 2030, including the interruption of g HAT transmission, is achievable. As the numbers of reported cases diminish, resources for surveillance and specialized screening also taper. This decrease, coupled with the loss of diagnostic skills and disease management expertise, could lead to a weak and less specialized HAT technical environment. Several therapeutic options are currently available to treat g-HAT at either the hemolymphatic (early) stage or meningoencephalitic (late) stage. In December 2018, fexinidazole was registered for the treatment of g-HAT in DRC. Since then, all other endemic countries authorized the use of fexinidazole for the treatment of g-HAT. Fexinidazole is administered as a 10 day oral treatment to patients with early- or late-stage g-HAT. In patients with very advanced g-HAT, nifurtimox eflornithine combination therapy (NECT) remains the first line treatment, due to the increased risk of relapse in these patients when treated with fexinidazole. Children with g-HAT who have a body weight below 20 kg and/or are under 6 years of age are treated with pentamidine (early stage) or NECT (late stage). Pentamidine and NECT are administered as intravenous (IV) infusions performed daily, over 7 days. Whilst the delivery of fexinidazole has simplified the management of g-HAT and has facilitated the integration of g-HAT treatment into general health systems, it is expected that the current investment in acoziborole as an oral, single-dose treatment will help boost elimination efforts envisioned for all stages of g-HAT. Indeed, treatment with NECT and fexinidazole are conditioned by the demonstration of the parasite in any body fluid via microscopy. However, factors such as low parasitemia as well as the complexity of parasitological diagnostic methods make this demonstration difficult. Acoziborole, as a single-dose oral administration, was studied in the open-label pivotal Phase II/III study (DNDi-OXA-02-HAT). The study was conducted in patients with g-HAT (all stages) in the DRC and Guinea. The results of the study showed the high efficacy of acoziborole in any stage of g-HAT, which was comparable to the efficacy of the reference treatment NECT used as a yardstick. Safety data collected during this study did not identify any new safety signals. Based on these data, the benefit-risk balance for treating g-HAT patients (regardless of the disease stage) with acoziborole administered as a single oral dose of 960 mg appeared favorable. The present study (DNDi-OXA-04-HAT) was conducted in g-HAT seropositive individuals who were unconfirmed parasitologically. It was designed with the objective of assessing the safety and tolerability of a single 960-mg dose of acoziborole compared with placebo during a follow-up period of 4 months. This study included an exploratory Sub-Study named TrypSkin which had the main objective of assessing the presence of extravascular dermal T.b. gambiense in the enrolled population. Participation in this Sub-Study was optional.
Interventions
DRUGAcoziborole
Single dose administration of acoziborole (3 tablets of 320 mg) on Day 1
DRUGPlacebo
Single dose administration of placebo (3 tablets of 320 mg) on Day 1
Sponsors
Drugs for Neglected Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind, placebo controlled study
Intervention model description
Unbalanced, randomized (ratio of 3:1 \[acoziborole:placebo\]) parallel-arm study. Study treatment (acoziborole or placebo) administered on Day 1. Post-treatment hospitalization of 5 days (up to Day 5). Follow-up visits scheduled at Month 1 and Month 4 (End of Study visit).
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed the informed consent form (ICF) * Male or female * 15 years of age or older * Card agglutination test for trypanosomiasis (CATT) test or HAT sero-K-set rapid diagnostic test (RDT) positive * Parasitology negative (in blood and/or lymph node aspirate \[if lymphadenopathy is present\]) * Karnofsky performance status above 70 * Able to ingest oral tablets * Known address and/or contact details provided * Able to comply with the schedule of follow-up visits and other requirements of the study * Agreement to be hospitalized upon enrolment for at least 5 days (in order to receive in-ward post-treatment observational follow-up through the first 5 days after treatment) * Agreement to not take part in any other clinical trials during the participation in this study * For women of childbearing potential: * Agreed to have protected sexual relations to avoid becoming pregnant from enrolment up to 3 months after dosing (contraceptive protection was advised and offered at no cost) * Negative urine pregnancy tests (before dosing at site level)
Exclusion criteria
* Individuals parasitologically confirmed in blood and/or lymph * Previously treated for g-HAT * Severe malnutrition, defined as body mass index (BMI) \<16 kg/m\^2 * Pregnant or breast-feeding women * For women of childbearing potential: * Urine pregnancy test positive * Did not accept contraceptive protection (i.e. condom or sexual abstinence) from enrolment up to 3 months after dosing * Clinically significant medical condition and/or abnormal laboratory results that could, in the opinion of the Investigator, jeopardize the participant's safety or participation in the study Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Any TEAEs | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of any TEAEs. |
| Occurrence of TEAEs - Malaria | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm). |
| Occurrence of TEAEs - Acarodermatitis | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm). |
| Occurrence of TEAEs - Abdominal Pain | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm). |
| Occurrence of TEAEs - Enteritis | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm). |
| Occurrence of TEAEs - Nausea | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm). |
| Occurrence of TEAEs - Gastritis | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm). |
| Occurrence of TEAEs - Headache | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm). |
| Occurrence of TEAEs - Fatigue | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm). |
| Occurrence of TEAEs - Blood Potassium Increased | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm). |
| Occurrence of TEAEs by Period of Occurrence | During hospitalization: from investigational product administration (Day 1) to Day 5 (End of Hospitalization); After hospitalization: from Day 5 (discharge) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of any TEAEs, by period of occurrence. |
| Occurrence of Serious TEAEs | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of any serious TEAEs. |
| Occurrence of Severe Treatment-related TEAEs | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence and excess rate (95% CI) of any serious TEAEs. |
| Occurrence of Any Treatment-related TEAEs | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence of any treatment-related TEAEs by arm |
| Occurrence of Treatment-related TEAEs by PT | From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study). | Occurrence of any treatment-related TEAEs by PT and by arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Biochemistry Parameter: Total Bilirubin | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Bicarbonate | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Hematology Parameter: Leukocytes | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in ECG (Electrocardiogram) Parameter: Heart Rate (HR) | From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization) | Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an analysis of covariance (ANCOVA) model adjusted for sex and age. |
| Change From Baseline in ECG Parameter: RR Interval | From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization) | Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age. |
| Change From Baseline in ECG Parameter: PR Interval | From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization) | Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age. |
| Change From Baseline in ECG Parameter: QRS Interval | From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization) | Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusting for sex and age. |
| Change From Baseline in ECG Parameter: QT Interval | From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization) | Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age. |
| Change From Baseline in ECG Parameter: QTcF | From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization) | Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age. |
| Change From Baseline in ECG Parameter: QTcB | From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization) | Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age. |
| Placebo-corrected Baseline-adjusted QTcF (ΔΔQTcF), Computed From a Concentration-response (C-R) Model Between Dry Blood Spot Concentration and Changes From Baseline in QTcF Parameter | From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization) | Mixed linear model developed based on the model defined by Garnett et al (2017). The fixed effect parameters of the pre-specified model were intercept, slope for acoziborole concentrations, influence of baseline (centered on mean), and a treatment specific intercept (0=acoziborole, 1=Placebo). Sex and age were included in the model as fixed covariates. |
| Change From Baseline in Biochemistry Parameter: Total Protein | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization) | Incidence of abnormal values for PR, QRS, QTcB and QTcF at Day 1 and/or Day 5, according to pre-defined thresholds |
| Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Hematology Parameter: Hemoglobin | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Hematology Parameter: Platelet Count | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Occurrence of Adverse Events (AEs) | From Inform Consent signature (up to 2 days before treatment) to the Month 4 follow up visit (End of Study) | Occurrence of any Adverse Event from Inform Consent signature to 4 month follow-up visit. Of note, all AEs reported during this study were TEAEs. |
| Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Albumin | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Calcium | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Chloride | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Creatinine | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Glucose | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Potassium | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
| Change From Baseline in Biochemistry Parameter: Sodium | From baseline to the Month 4 follow-up visit (End of Study). | Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm. |
Countries
Democratic Republic of the Congo, Guinea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acoziborole Acoziborole: 3 tablets of 320 mg | 906 |
| Placebo Placebo: 3 tablets of 320 mg | 300 |
| Total | 1,206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up | Death | 0 | 1 |
| Follow-up | Lost to Follow-up | 7 | 1 |
| Follow-up | Withdrawal by Subject | 1 | 0 |
| Treatment Period | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Acoziborole | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 17.35 | 36.4 years STANDARD_DEVIATION 16.38 | 37.1 years STANDARD_DEVIATION 17.11 |
| Age, Customized Adolescent (15-17 years) | 101 Participants | 28 Participants | 129 Participants |
| Age, Customized Adult (≥18 years) | 805 Participants | 272 Participants | 1077 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 906 Participants | 300 Participants | 1206 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Guinea | 132 Participants | 44 Participants | 176 Participants |
| Region of Enrollment Republic of the Congo | 774 Participants | 256 Participants | 1030 Participants |
| Sex: Female, Male Female | 476 Participants | 158 Participants | 634 Participants |
| Sex: Female, Male Male | 430 Participants | 142 Participants | 572 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 906 | 1 / 300 |
| other Total, other adverse events | 137 / 906 | 45 / 300 |
| serious Total, serious adverse events | 3 / 906 | 4 / 300 |
Outcome results
Primary
Occurrence of Any TEAEs
Occurrence and excess rate (95% CI) of any TEAEs.
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of Any TEAEs | 195 Participants |
| Placebo | Occurrence of Any TEAEs | 69 Participants |
95% CI: [-7.2, 3.7]
Primary
Occurrence of Any Treatment-related TEAEs
Occurrence of any treatment-related TEAEs by arm
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of Any Treatment-related TEAEs | 59 Participants |
| Placebo | Occurrence of Any Treatment-related TEAEs | 17 Participants |
Primary
Occurrence of Serious TEAEs
Occurrence and excess rate (95% CI) of any serious TEAEs.
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of Serious TEAEs | 3 Participants |
| Placebo | Occurrence of Serious TEAEs | 4 Participants |
95% CI: [-3.1, 0]
Primary
Occurrence of Severe Treatment-related TEAEs
Occurrence and excess rate (95% CI) of any serious TEAEs.
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of Severe Treatment-related TEAEs | 0 Participants |
| Placebo | Occurrence of Severe Treatment-related TEAEs | 0 Participants |
Primary
Occurrence of TEAEs - Abdominal Pain
Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of TEAEs - Abdominal Pain | 23 Participants |
| Placebo | Occurrence of TEAEs - Abdominal Pain | 9 Participants |
95% CI: [-3.2, 1.4]
Primary
Occurrence of TEAEs - Acarodermatitis
Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of TEAEs - Acarodermatitis | 13 Participants |
| Placebo | Occurrence of TEAEs - Acarodermatitis | 3 Participants |
95% CI: [-1.6, 1.6]
Primary
Occurrence of TEAEs - Blood Potassium Increased
Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of TEAEs - Blood Potassium Increased | 8 Participants |
| Placebo | Occurrence of TEAEs - Blood Potassium Increased | 6 Participants |
95% CI: [-3.5, 0.3]
Primary
Occurrence of TEAEs by Period of Occurrence
Occurrence and excess rate (95% CI) of any TEAEs, by period of occurrence.
Time frame: During hospitalization: from investigational product administration (Day 1) to Day 5 (End of Hospitalization); After hospitalization: from Day 5 (discharge) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Acoziborole | Occurrence of TEAEs by Period of Occurrence | During hospitalization | 124 participants |
| Acoziborole | Occurrence of TEAEs by Period of Occurrence | After hospitalization | 106 participants |
| Placebo | Occurrence of TEAEs by Period of Occurrence | During hospitalization | 38 participants |
| Placebo | Occurrence of TEAEs by Period of Occurrence | After hospitalization | 45 participants |
Comparison: Occurrence and excess rate (95% CI) of any TEAEs reported during hospitalization.95% CI: [-3.7, 5.1]
Comparison: Occurrence and excess rate (95% CI) of any TEAEs reported after the hospitalization period.95% CI: [-8.2, 0.9]
Primary
Occurrence of TEAEs - Enteritis
Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of TEAEs - Enteritis | 7 Participants |
| Placebo | Occurrence of TEAEs - Enteritis | 4 Participants |
95% CI: [-2.6, 0.6]
Primary
Occurrence of TEAEs - Fatigue
Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of TEAEs - Fatigue | 14 Participants |
| Placebo | Occurrence of TEAEs - Fatigue | 5 Participants |
95% CI: [-2.4, 1.3]
Primary
Occurrence of TEAEs - Gastritis
Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of TEAEs - Gastritis | 6 Participants |
| Placebo | Occurrence of TEAEs - Gastritis | 3 Participants |
95% CI: [-2.3, 0.7]
Primary
Occurrence of TEAEs - Headache
Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of TEAEs - Headache | 53 Participants |
| Placebo | Occurrence of TEAEs - Headache | 8 Participants |
95% CI: [0.3, 5.3]
Primary
Occurrence of TEAEs - Malaria
Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of TEAEs - Malaria | 34 Participants |
| Placebo | Occurrence of TEAEs - Malaria | 14 Participants |
Comparison: Occurrence and excess rate (95% CI) of any TEAEs (by PT, for PTs reported in ≥1% of participants in either arm) from the investigational product administration (Day 1) to the Month 4 follow-up visit.95% CI: [-4.1, 1.4]
Primary
Occurrence of TEAEs - Nausea
Occurrence and excess rate (95% CI) of common TEAEs (by PT, for PTs reported in ≥1% of participants in either arm).
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of TEAEs - Nausea | 7 Participants |
| Placebo | Occurrence of TEAEs - Nausea | 3 Participants |
95% CI: [-2.2, 0.8]
Primary
Occurrence of Treatment-related TEAEs by PT
Occurrence of any treatment-related TEAEs by PT and by arm
Time frame: From the investigational product administration (Day 1) to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Abdominal pain | 14 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Vomiting | 1 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Nausea | 5 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Dysgeusia | 1 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | SOC: Nervous system disorders | 28 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Diarrhoea | 1 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Dizziness | 5 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Enteritis | 1 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Fatigue | 8 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Dyspepsia | 1 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Hot flush | 3 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Gastrointestinal sounds abnormal | 1 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Tachycardia | 0 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Asthenia | 1 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Pyrexia | 2 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Electrocardiogram QT prolonged | 1 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Decreased appetite | 6 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Muscle spasms | 1 Participants |
| Acoziborole | Occurrence of Treatment-related TEAEs by PT | Insomia | 2 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Tachycardia | 1 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | SOC: Nervous system disorders | 5 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Abdominal pain | 6 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Fatigue | 5 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Decreased appetite | 1 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Nausea | 2 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Dizziness | 1 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Hot flush | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Pyrexia | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Insomia | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Vomiting | 1 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Dysgeusia | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Diarrhoea | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Enteritis | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Dyspepsia | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Gastrointestinal sounds abnormal | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Asthenia | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Electrocardiogram QT prolonged | 0 Participants |
| Placebo | Occurrence of Treatment-related TEAEs by PT | Muscle spasms | 0 Participants |
Secondary
Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase | Baseline | 20.6 U/L | Standard Deviation 7.9 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase | Day 5 | 21.9 U/L | Standard Deviation 9.1 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase | Month 1 | 19.2 U/L | Standard Deviation 7.87 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase | Month 4 | 20.8 U/L | Standard Deviation 8.05 |
| Placebo | Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase | Month 4 | 20.0 U/L | Standard Deviation 6.71 |
| Placebo | Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase | Baseline | 20.6 U/L | Standard Deviation 9.44 |
| Placebo | Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase | Month 1 | 19.5 U/L | Standard Deviation 11.7 |
| Placebo | Change From Baseline in Biochemistry Parameter: Alanine Aminotransferase | Day 5 | 24.9 U/L | Standard Deviation 13.42 |
Secondary
Change From Baseline in Biochemistry Parameter: Albumin
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Albumin | Baseline | 3.22 g/dL | Standard Deviation 0.471 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Albumin | Day 5 | 3.12 g/dL | Standard Deviation 0.434 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Albumin | Month 1 | 3.27 g/dL | Standard Deviation 0.413 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Albumin | Month 4 | 3.22 g/dL | Standard Deviation 0.416 |
| Placebo | Change From Baseline in Biochemistry Parameter: Albumin | Month 4 | 3.21 g/dL | Standard Deviation 0.398 |
| Placebo | Change From Baseline in Biochemistry Parameter: Albumin | Baseline | 3.23 g/dL | Standard Deviation 0.433 |
| Placebo | Change From Baseline in Biochemistry Parameter: Albumin | Month 1 | 3.24 g/dL | Standard Deviation 0.391 |
| Placebo | Change From Baseline in Biochemistry Parameter: Albumin | Day 5 | 3.13 g/dL | Standard Deviation 0.414 |
Secondary
Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase | Baseline | 99.8 U/L | Standard Deviation 46.71 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase | Day 5 | 91.9 U/L | Standard Deviation 40.18 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase | Month 1 | 96.6 U/L | Standard Deviation 47.88 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase | Month 4 | 98.6 U/L | Standard Deviation 44.85 |
| Placebo | Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase | Month 4 | 98.1 U/L | Standard Deviation 49.9 |
| Placebo | Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase | Baseline | 101.8 U/L | Standard Deviation 52.59 |
| Placebo | Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase | Month 1 | 98.3 U/L | Standard Deviation 53.97 |
| Placebo | Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase | Day 5 | 95.7 U/L | Standard Deviation 46.43 |
Secondary
Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase | Baseline | 32.8 U/L | Standard Deviation 10.2 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase | Day 5 | 33.8 U/L | Standard Deviation 11.21 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase | Month 1 | 31.0 U/L | Standard Deviation 9.5 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase | Month 4 | 31.8 U/L | Standard Deviation 10.95 |
| Placebo | Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase | Month 4 | 31.1 U/L | Standard Deviation 8.51 |
| Placebo | Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase | Baseline | 32.7 U/L | Standard Deviation 12.41 |
| Placebo | Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase | Month 1 | 32.6 U/L | Standard Deviation 30.32 |
| Placebo | Change From Baseline in Biochemistry Parameter: Aspartate Aminotransferase | Day 5 | 37.2 U/L | Standard Deviation 19.04 |
Secondary
Change From Baseline in Biochemistry Parameter: Bicarbonate
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Bicarbonate | Baseline | 27.5 mmol/L | Standard Deviation 2.46 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Bicarbonate | Day 5 | 28.5 mmol/L | Standard Deviation 2.39 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Bicarbonate | Month 1 | 28.0 mmol/L | Standard Deviation 2.5 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Bicarbonate | Month 4 | 28.0 mmol/L | Standard Deviation 2.48 |
| Placebo | Change From Baseline in Biochemistry Parameter: Bicarbonate | Month 4 | 27.9 mmol/L | Standard Deviation 2.58 |
| Placebo | Change From Baseline in Biochemistry Parameter: Bicarbonate | Baseline | 27.5 mmol/L | Standard Deviation 2.6 |
| Placebo | Change From Baseline in Biochemistry Parameter: Bicarbonate | Month 1 | 27.7 mmol/L | Standard Deviation 2.44 |
| Placebo | Change From Baseline in Biochemistry Parameter: Bicarbonate | Day 5 | 28.2 mmol/L | Standard Deviation 2.4 |
Secondary
Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen | Baseline | 7.434 mg/dL | Standard Deviation 2.5471 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen | Day 5 | 8.402 mg/dL | Standard Deviation 2.6432 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen | Month 1 | 6.951 mg/dL | Standard Deviation 2.2998 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen | Month 4 | 7.501 mg/dL | Standard Deviation 2.3841 |
| Placebo | Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen | Month 4 | 7.383 mg/dL | Standard Deviation 2.2759 |
| Placebo | Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen | Baseline | 7.415 mg/dL | Standard Deviation 2.655 |
| Placebo | Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen | Month 1 | 6.820 mg/dL | Standard Deviation 2.5365 |
| Placebo | Change From Baseline in Biochemistry Parameter: Blood Urea Nitrogen | Day 5 | 8.358 mg/dL | Standard Deviation 2.4459 |
Secondary
Change From Baseline in Biochemistry Parameter: Calcium
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Calcium | Baseline | 2.314 mmol/L | Standard Deviation 0.1341 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Calcium | Day 5 | 2.279 mmol/L | Standard Deviation 0.1681 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Calcium | Month 1 | 2.305 mmol/L | Standard Deviation 0.1499 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Calcium | Month 4 | 2.297 mmol/L | Standard Deviation 0.1399 |
| Placebo | Change From Baseline in Biochemistry Parameter: Calcium | Month 4 | 2.297 mmol/L | Standard Deviation 0.1514 |
| Placebo | Change From Baseline in Biochemistry Parameter: Calcium | Baseline | 2.322 mmol/L | Standard Deviation 0.1216 |
| Placebo | Change From Baseline in Biochemistry Parameter: Calcium | Month 1 | 2.298 mmol/L | Standard Deviation 0.1904 |
| Placebo | Change From Baseline in Biochemistry Parameter: Calcium | Day 5 | 2.328 mmol/L | Standard Deviation 0.155 |
Secondary
Change From Baseline in Biochemistry Parameter: Chloride
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Chloride | Baseline | 105.3 mmol/L | Standard Deviation 3.05 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Chloride | Day 5 | 105.2 mmol/L | Standard Deviation 3.22 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Chloride | Month 1 | 105.1 mmol/L | Standard Deviation 3.04 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Chloride | Month 5 | 104.8 mmol/L | Standard Deviation 2.89 |
| Placebo | Change From Baseline in Biochemistry Parameter: Chloride | Month 5 | 104.8 mmol/L | Standard Deviation 3.18 |
| Placebo | Change From Baseline in Biochemistry Parameter: Chloride | Baseline | 105.3 mmol/L | Standard Deviation 2.74 |
| Placebo | Change From Baseline in Biochemistry Parameter: Chloride | Month 1 | 105.0 mmol/L | Standard Deviation 3.23 |
| Placebo | Change From Baseline in Biochemistry Parameter: Chloride | Day 5 | 105.2 mmol/L | Standard Deviation 3.53 |
Secondary
Change From Baseline in Biochemistry Parameter: Creatinine
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Creatinine | Baseline | 0.84 mg/dL | Standard Deviation 0.238 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Creatinine | Day 5 | 0.83 mg/dL | Standard Deviation 0.256 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Creatinine | Month 1 | 0.82 mg/dL | Standard Deviation 0.23 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Creatinine | Month 4 | 0.81 mg/dL | Standard Deviation 0.227 |
| Placebo | Change From Baseline in Biochemistry Parameter: Creatinine | Month 4 | 0.80 mg/dL | Standard Deviation 0.223 |
| Placebo | Change From Baseline in Biochemistry Parameter: Creatinine | Baseline | 0.84 mg/dL | Standard Deviation 0.23 |
| Placebo | Change From Baseline in Biochemistry Parameter: Creatinine | Month 1 | 0.81 mg/dL | Standard Deviation 0.22 |
| Placebo | Change From Baseline in Biochemistry Parameter: Creatinine | Day 5 | 0.81 mg/dL | Standard Deviation 0.233 |
Secondary
Change From Baseline in Biochemistry Parameter: Glucose
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Glucose | Baseline | 88.581 mg/dL | Standard Deviation 19.954 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Glucose | Day 5 | 89.801 mg/dL | Standard Deviation 14.4784 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Glucose | Month 1 | 91.715 mg/dL | Standard Deviation 16.4756 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Glucose | Month 4 | 91.226 mg/dL | Standard Deviation 24.444 |
| Placebo | Change From Baseline in Biochemistry Parameter: Glucose | Month 4 | 89.225 mg/dL | Standard Deviation 10.2205 |
| Placebo | Change From Baseline in Biochemistry Parameter: Glucose | Baseline | 87.087 mg/dL | Standard Deviation 11.3391 |
| Placebo | Change From Baseline in Biochemistry Parameter: Glucose | Month 1 | 90.207 mg/dL | Standard Deviation 10.8139 |
| Placebo | Change From Baseline in Biochemistry Parameter: Glucose | Day 5 | 89.410 mg/dL | Standard Deviation 9.9699 |
Secondary
Change From Baseline in Biochemistry Parameter: Potassium
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Potassium | Baseline | 4.58 mmol/L | Standard Deviation 0.537 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Potassium | Day 5 | 4.67 mmol/L | Standard Deviation 0.607 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Potassium | Month 1 | 4.61 mmol/L | Standard Deviation 0.589 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Potassium | Month 4 | 4.59 mmol/L | Standard Deviation 0.54 |
| Placebo | Change From Baseline in Biochemistry Parameter: Potassium | Month 4 | 4.61 mmol/L | Standard Deviation 0.55 |
| Placebo | Change From Baseline in Biochemistry Parameter: Potassium | Baseline | 4.60 mmol/L | Standard Deviation 0.572 |
| Placebo | Change From Baseline in Biochemistry Parameter: Potassium | Month 1 | 4.60 mmol/L | Standard Deviation 0.636 |
| Placebo | Change From Baseline in Biochemistry Parameter: Potassium | Day 5 | 4.59 mmol/L | Standard Deviation 0.559 |
Secondary
Change From Baseline in Biochemistry Parameter: Sodium
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Sodium | Baseline | 136.7 mmol/L | Standard Deviation 3.39 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Sodium | Day 5 | 137.2 mmol/L | Standard Deviation 3.75 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Sodium | Month 1 | 137.2 mmol/L | Standard Deviation 3.41 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Sodium | Month 4 | 137.1 mmol/L | Standard Deviation 3.36 |
| Placebo | Change From Baseline in Biochemistry Parameter: Sodium | Month 4 | 137.0 mmol/L | Standard Deviation 3.38 |
| Placebo | Change From Baseline in Biochemistry Parameter: Sodium | Baseline | 136.7 mmol/L | Standard Deviation 3.61 |
| Placebo | Change From Baseline in Biochemistry Parameter: Sodium | Month 1 | 137.1 mmol/L | Standard Deviation 3.94 |
| Placebo | Change From Baseline in Biochemistry Parameter: Sodium | Day 5 | 137.1 mmol/L | Standard Deviation 3.97 |
Secondary
Change From Baseline in Biochemistry Parameter: Total Bilirubin
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Total Bilirubin | Baseline | 0.879 mg/dL | Standard Deviation 0.3457 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Total Bilirubin | Day 5 | 0.739 mg/dL | Standard Deviation 0.2957 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Total Bilirubin | Month 1 | 0.818 mg/dL | Standard Deviation 0.2641 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Total Bilirubin | Month 4 | 0.887 mg/dL | Standard Deviation 0.318 |
| Placebo | Change From Baseline in Biochemistry Parameter: Total Bilirubin | Month 4 | 0.902 mg/dL | Standard Deviation 0.2937 |
| Placebo | Change From Baseline in Biochemistry Parameter: Total Bilirubin | Baseline | 0.869 mg/dL | Standard Deviation 0.3469 |
| Placebo | Change From Baseline in Biochemistry Parameter: Total Bilirubin | Month 1 | 0.884 mg/dL | Standard Deviation 0.2591 |
| Placebo | Change From Baseline in Biochemistry Parameter: Total Bilirubin | Day 5 | 0.809 mg/dL | Standard Deviation 0.2506 |
Secondary
Change From Baseline in Biochemistry Parameter: Total Protein
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Biochemistry Parameter: Total Protein | Baseline | 7.63 g/dL | Standard Deviation 0.589 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Total Protein | Day 5 | 7.46 g/dL | Standard Deviation 0.566 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Total Protein | Month 1 | 7.55 g/dL | Standard Deviation 0.547 |
| Acoziborole | Change From Baseline in Biochemistry Parameter: Total Protein | Month 4 | 7.54 g/dL | Standard Deviation 0.573 |
| Placebo | Change From Baseline in Biochemistry Parameter: Total Protein | Month 4 | 7.57 g/dL | Standard Deviation 0.591 |
| Placebo | Change From Baseline in Biochemistry Parameter: Total Protein | Baseline | 7.65 g/dL | Standard Deviation 0.565 |
| Placebo | Change From Baseline in Biochemistry Parameter: Total Protein | Month 1 | 7.59 g/dL | Standard Deviation 0.583 |
| Placebo | Change From Baseline in Biochemistry Parameter: Total Protein | Day 5 | 7.61 g/dL | Standard Deviation 0.584 |
Secondary
Change From Baseline in ECG (Electrocardiogram) Parameter: Heart Rate (HR)
Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an analysis of covariance (ANCOVA) model adjusted for sex and age.
Time frame: From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization)
Population: ECG central tendency set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data) and who had valid ECG evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in ECG (Electrocardiogram) Parameter: Heart Rate (HR) | Day 1 (pre-dose) | 66.8 beats/min | Standard Deviation 10.7 |
| Acoziborole | Change From Baseline in ECG (Electrocardiogram) Parameter: Heart Rate (HR) | Day 5 | 66.4 beats/min | Standard Deviation 9.9 |
| Acoziborole | Change From Baseline in ECG (Electrocardiogram) Parameter: Heart Rate (HR) | Change from baseline at Day 5 (Δ) | -0.4 beats/min | Standard Deviation 8.4 |
| Placebo | Change From Baseline in ECG (Electrocardiogram) Parameter: Heart Rate (HR) | Day 1 (pre-dose) | 70.0 beats/min | Standard Deviation 12.1 |
| Placebo | Change From Baseline in ECG (Electrocardiogram) Parameter: Heart Rate (HR) | Day 5 | 69.1 beats/min | Standard Deviation 12.6 |
| Placebo | Change From Baseline in ECG (Electrocardiogram) Parameter: Heart Rate (HR) | Change from baseline at Day 5 (Δ) | -0.9 beats/min | Standard Deviation 8.3 |
Comparison: Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.90% CI: [-2.1, 1.4]
Secondary
Change From Baseline in ECG Parameter: PR Interval
Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.
Time frame: From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization)
Population: ECG central tendency set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data) and who had valid ECG evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in ECG Parameter: PR Interval | Day 1 (pre-dose) | 162.4 ms | Standard Deviation 25.2 |
| Acoziborole | Change From Baseline in ECG Parameter: PR Interval | Day 5 | 161.4 ms | Standard Deviation 23 |
| Acoziborole | Change From Baseline in ECG Parameter: PR Interval | Change from baseline at Day 5 (Δ) | -1.0 ms | Standard Deviation 1.11 |
| Placebo | Change From Baseline in ECG Parameter: PR Interval | Day 1 (pre-dose) | 162.2 ms | Standard Deviation 20.3 |
| Placebo | Change From Baseline in ECG Parameter: PR Interval | Day 5 | 161.9 ms | Standard Deviation 20.5 |
| Placebo | Change From Baseline in ECG Parameter: PR Interval | Change from baseline at Day 5 (Δ) | -0.3 ms | Standard Deviation 12.8 |
Comparison: Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.90% CI: [-3.6, 1.3]
Secondary
Change From Baseline in ECG Parameter: QRS Interval
Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusting for sex and age.
Time frame: From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in ECG Parameter: QRS Interval | Day 1 (pre-dose) | 82.2 ms | Standard Deviation 8.2 |
| Acoziborole | Change From Baseline in ECG Parameter: QRS Interval | Day 5 | 81.8 ms | Standard Deviation 8.4 |
| Acoziborole | Change From Baseline in ECG Parameter: QRS Interval | Change from baseline at Day 5 (Δ) | -0.5 ms | Standard Deviation 5.4 |
| Placebo | Change From Baseline in ECG Parameter: QRS Interval | Day 1 (pre-dose) | 82.3 ms | Standard Deviation 10.2 |
| Placebo | Change From Baseline in ECG Parameter: QRS Interval | Day 5 | 82.5 ms | Standard Deviation 9 |
| Placebo | Change From Baseline in ECG Parameter: QRS Interval | Change from baseline at Day 5 (Δ) | 0.3 ms | Standard Deviation 4.5 |
Comparison: Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.90% CI: [-1.9, 0.4]
Secondary
Change From Baseline in ECG Parameter: QTcB
Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.
Time frame: From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization)
Population: ECG central tendency set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data) and who had valid ECG evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in ECG Parameter: QTcB | Day 1 (pre-dose) | 407.9 ms | Standard Deviation 23 |
| Acoziborole | Change From Baseline in ECG Parameter: QTcB | Day 5 | 394.6 ms | Standard Deviation 23.3 |
| Acoziborole | Change From Baseline in ECG Parameter: QTcB | Change from baseline at Day 5 (Δ) | -13.3 ms | Standard Deviation 14.2 |
| Placebo | Change From Baseline in ECG Parameter: QTcB | Day 1 (pre-dose) | 410.1 ms | Standard Deviation 25.8 |
| Placebo | Change From Baseline in ECG Parameter: QTcB | Day 5 | 407.8 ms | Standard Deviation 24.6 |
| Placebo | Change From Baseline in ECG Parameter: QTcB | Change from baseline at Day 5 (Δ) | -2.3 ms | Standard Deviation 14.8 |
Comparison: Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.90% CI: [-14.9, -8.6]
Secondary
Change From Baseline in ECG Parameter: QTcF
Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.
Time frame: From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization)
Population: ECG central tendency set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data) and who had valid ECG evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in ECG Parameter: QTcF | Day 1 (pre-dose) | 401.3 ms | Standard Deviation 20 |
| Acoziborole | Change From Baseline in ECG Parameter: QTcF | Day 5 | 388.5 ms | Standard Deviation 20.5 |
| Acoziborole | Change From Baseline in ECG Parameter: QTcF | Change from baseline at Day 5 (Δ) | -12.8 ms | Standard Deviation 13.3 |
| Placebo | Change From Baseline in ECG Parameter: QTcF | Day 1 (pre-dose) | 400.5 ms | Standard Deviation 24 |
| Placebo | Change From Baseline in ECG Parameter: QTcF | Day 5 | 399.0 ms | Standard Deviation 21.8 |
| Placebo | Change From Baseline in ECG Parameter: QTcF | Change from baseline at Day 5 (Δ) | -1.5 ms | Standard Deviation 13.8 |
Comparison: Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.90% CI: [-14.4, -8.7]
Secondary
Change From Baseline in ECG Parameter: QT Interval
Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.
Time frame: From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization)
Population: ECG central tendency set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data) and who had valid ECG evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in ECG Parameter: QT Interval | Day 1 (pre-dose) | 389.5 ms | Standard Deviation 27.8 |
| Acoziborole | Change From Baseline in ECG Parameter: QT Interval | Day 5 | 377.3 ms | Standard Deviation 26.7 |
| Acoziborole | Change From Baseline in ECG Parameter: QT Interval | Change from baseline at Day 5 (Δ) | -12.1 ms | Standard Deviation 21.4 |
| Placebo | Change From Baseline in ECG Parameter: QT Interval | Day 1 (pre-dose) | 383.0 ms | Standard Deviation 33.1 |
| Placebo | Change From Baseline in ECG Parameter: QT Interval | Day 5 | 383.1 ms | Standard Deviation 30.8 |
| Placebo | Change From Baseline in ECG Parameter: QT Interval | Change from baseline at Day 5 (Δ) | 0.1 ms | Standard Deviation 20.4 |
Comparison: Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.90% CI: [-15.3, -6.6]
Secondary
Change From Baseline in ECG Parameter: RR Interval
Actual values at baseline (Day 1 pre-dose) and Day 5. Change from baseline at Day 5 (Δ). Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.
Time frame: From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization)
Population: ECG central tendency set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data) and who had valid ECG evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in ECG Parameter: RR Interval | Day 1 (pre-dose) | 921.6 ms | Standard Deviation 143.8 |
| Acoziborole | Change From Baseline in ECG Parameter: RR Interval | Day 5 | 923.5 ms | Standard Deviation 137.4 |
| Acoziborole | Change From Baseline in ECG Parameter: RR Interval | Change from baseline at Day 5 (Δ) | 1.9 ms | Standard Deviation 103.5 |
| Placebo | Change From Baseline in ECG Parameter: RR Interval | Day 1 (pre-dose) | 882.2 ms | Standard Deviation 149.3 |
| Placebo | Change From Baseline in ECG Parameter: RR Interval | Day 5 | 893.7 ms | Standard Deviation 149.4 |
| Placebo | Change From Baseline in ECG Parameter: RR Interval | Change from baseline at Day 5 (Δ) | 11.5 ms | Standard Deviation 94.8 |
Comparison: Placebo-corrected change from baseline (ΔΔ), calculated using an ANCOVA model adjusted for sex and age.90% CI: [-22, 21.1]
Secondary
Change From Baseline in Hematology Parameter: Hemoglobin
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Hematology Parameter: Hemoglobin | Baseline | 13.09 g/dL | Standard Deviation 1.706 |
| Acoziborole | Change From Baseline in Hematology Parameter: Hemoglobin | Day 5 | 12.57 g/dL | Standard Deviation 1.627 |
| Acoziborole | Change From Baseline in Hematology Parameter: Hemoglobin | Month 1 | 12.78 g/dL | Standard Deviation 1.55 |
| Acoziborole | Change From Baseline in Hematology Parameter: Hemoglobin | Month 4 | 13.04 g/dL | Standard Deviation 1.644 |
| Placebo | Change From Baseline in Hematology Parameter: Hemoglobin | Month 4 | 12.93 g/dL | Standard Deviation 1.646 |
| Placebo | Change From Baseline in Hematology Parameter: Hemoglobin | Baseline | 13.10 g/dL | Standard Deviation 1.554 |
| Placebo | Change From Baseline in Hematology Parameter: Hemoglobin | Month 1 | 13.00 g/dL | Standard Deviation 1.489 |
| Placebo | Change From Baseline in Hematology Parameter: Hemoglobin | Day 5 | 12.95 g/dL | Standard Deviation 1.513 |
Secondary
Change From Baseline in Hematology Parameter: Leukocytes
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Hematology Parameter: Leukocytes | Baseline | 5.53 10^9 Leukocytes/L | Standard Deviation 1.576 |
| Acoziborole | Change From Baseline in Hematology Parameter: Leukocytes | Day 5 | 5.64 10^9 Leukocytes/L | Standard Deviation 1.563 |
| Acoziborole | Change From Baseline in Hematology Parameter: Leukocytes | Month 1 | 5.51 10^9 Leukocytes/L | Standard Deviation 1.446 |
| Acoziborole | Change From Baseline in Hematology Parameter: Leukocytes | Month 4 | 5.49 10^9 Leukocytes/L | Standard Deviation 1.385 |
| Placebo | Change From Baseline in Hematology Parameter: Leukocytes | Month 4 | 5.52 10^9 Leukocytes/L | Standard Deviation 1.426 |
| Placebo | Change From Baseline in Hematology Parameter: Leukocytes | Baseline | 5.46 10^9 Leukocytes/L | Standard Deviation 1.539 |
| Placebo | Change From Baseline in Hematology Parameter: Leukocytes | Month 1 | 5.50 10^9 Leukocytes/L | Standard Deviation 1.427 |
| Placebo | Change From Baseline in Hematology Parameter: Leukocytes | Day 5 | 5.60 10^9 Leukocytes/L | Standard Deviation 1.507 |
Secondary
Change From Baseline in Hematology Parameter: Platelet Count
Changes from baseline to Day 5, Month 1 and Month 4; presented by treatment arm.
Time frame: From baseline to the Month 4 follow-up visit (End of Study).
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acoziborole | Change From Baseline in Hematology Parameter: Platelet Count | Baseline | 229.1 10^9 platelets/L | Standard Deviation 64.75 |
| Acoziborole | Change From Baseline in Hematology Parameter: Platelet Count | Day 5 | 230.5 10^9 platelets/L | Standard Deviation 65.2 |
| Acoziborole | Change From Baseline in Hematology Parameter: Platelet Count | Month 1 | 227.7 10^9 platelets/L | Standard Deviation 62.55 |
| Acoziborole | Change From Baseline in Hematology Parameter: Platelet Count | Month 4 | 228.4 10^9 platelets/L | Standard Deviation 60.29 |
| Placebo | Change From Baseline in Hematology Parameter: Platelet Count | Month 4 | 229.1 10^9 platelets/L | Standard Deviation 63.44 |
| Placebo | Change From Baseline in Hematology Parameter: Platelet Count | Baseline | 229.0 10^9 platelets/L | Standard Deviation 63.04 |
| Placebo | Change From Baseline in Hematology Parameter: Platelet Count | Month 1 | 227.6 10^9 platelets/L | Standard Deviation 64.01 |
| Placebo | Change From Baseline in Hematology Parameter: Platelet Count | Day 5 | 226.5 10^9 platelets/L | Standard Deviation 65.84 |
Secondary
Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds
Incidence of abnormal values for PR, QRS, QTcB and QTcF at Day 1 and/or Day 5, according to pre-defined thresholds
Time frame: From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization)
Population: ECG categorical analyses set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data) and who had valid ECG evaluations at Day 1 or Day 5.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | HR >120 beats/min | 0 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF >500 ms | 0 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QRS >120 ms | 1 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF change from baseline >30 ms and ≤60 ms | 0 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | PR >220 ms | 2 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF change from >60 ms | 0 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QRS relative change from baseline >25% | 0 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB >450 ms and ≤480 ms | 3 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | HR relative change from baseline >25% | 6 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB >480 ms and ≤500 ms | 1 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF >450 ms and ≤480 ms | 2 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB >500 ms | 0 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | PR relative change from baseline >25% | 0 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB change from baseline >30 ms and ≤60 ms | 1 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF >480 ms and ≤500 ms | 0 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB change from >60 ms | 0 Participants |
| Acoziborole | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | HR <40 beats/min | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB change from >60 ms | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | HR <40 beats/min | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | HR >120 beats/min | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | HR relative change from baseline >25% | 2 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | PR >220 ms | 1 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | PR relative change from baseline >25% | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QRS >120 ms | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QRS relative change from baseline >25% | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF >450 ms and ≤480 ms | 1 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF >480 ms and ≤500 ms | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF >500 ms | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF change from baseline >30 ms and ≤60 ms | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcF change from >60 ms | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB >450 ms and ≤480 ms | 1 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB >480 ms and ≤500 ms | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB >500 ms | 0 Participants |
| Placebo | Incidence of Abnormal Values for PR, QRS, QTcB and QTcF According to Pre-defined Thresholds | QTcB change from baseline >30 ms and ≤60 ms | 1 Participants |
Secondary
Occurrence of Adverse Events (AEs)
Occurrence of any Adverse Event from Inform Consent signature to 4 month follow-up visit. Of note, all AEs reported during this study were TEAEs.
Time frame: From Inform Consent signature (up to 2 days before treatment) to the Month 4 follow up visit (End of Study)
Population: Safety set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acoziborole | Occurrence of Adverse Events (AEs) | 195 Participants |
| Placebo | Occurrence of Adverse Events (AEs) | 69 Participants |
Comparison: Of note, all AEs reported during this study were TEAEs.95% CI: [-7.2, 3.7]
Secondary
Placebo-corrected Baseline-adjusted QTcF (ΔΔQTcF), Computed From a Concentration-response (C-R) Model Between Dry Blood Spot Concentration and Changes From Baseline in QTcF Parameter
Mixed linear model developed based on the model defined by Garnett et al (2017). The fixed effect parameters of the pre-specified model were intercept, slope for acoziborole concentrations, influence of baseline (centered on mean), and a treatment specific intercept (0=acoziborole, 1=Placebo). Sex and age were included in the model as fixed covariates.
Time frame: From baseline (Day 1 pre-dose) to Day 5 (End of Hospitalization)
Population: C-R analysis set: participants who received at least 1 tablet of the investigational product (based on the actual treatment received, confirmed by drug concentration data), who had valid ECG evaluations, and at least one change from baseline in ECG matching a PK sample.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Acoziborole | Placebo-corrected Baseline-adjusted QTcF (ΔΔQTcF), Computed From a Concentration-response (C-R) Model Between Dry Blood Spot Concentration and Changes From Baseline in QTcF Parameter | -12.9 ms |
Comparison: Estimated ΔΔQTcF (in ms) computed from a concentration-response (C-R) model between dry blood spot concentration of acoziborole and changes from baseline in QTcF parameter90% CI: [-13.5, -7.85]