Plasmodium Falciparum Malaria
Conditions
Keywords
Plasmodium falciparum, malaria, artemether, lumefantrine, neonates, infants
Brief summary
The purpose of this study was to evaluate PK, safety, tolerability and efficacy of a new formulation of artemether-lumefantrine dispersible tablet in neonates and infants \<5 kg body weight with acute uncomplicated Plasmodium falciparum malaria.
Detailed description
This was a multicenter, open-label, single-arm, adaptive design with dose adaptation (deescalation or escalation) study in infants and neonates \<5 kg body weight with P. falciparum malaria. There were two sequential and age-descending cohorts of participants, all \<5 kg: Cohort 1 of infants \>28 days of age, and Cohort 2 of neonates ≤ 28 days of age.
Interventions
DRUGartemether:lumefantrine (2.5 mg:30 mg)
Two oral dispersible tablets twice daily for three consecutive days. Each tablet contained artemether-lumefantrine 2.5 mg:30 mg.
Sponsors
European and Developing Countries Clinical Trials Partnership (EDCTP)
Medicines for Malaria Venture
Groupe de Recherche Action en Sante
Institut de Recherche en Sciences de la Sante, Burkina Faso
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 365 Days
Healthy volunteers
No
Inclusion criteria
1. Male or female neonates/infants 2. Body weight \<5 kg but ≥ 2 kg 3. In Cohort 1, infants aged \>28 days; in Cohort 2, neonates aged 1 to ≤28 days (3 subgroups: 1-7 days; 8-14 days; 15-28 days) 4. Microscopically confirmed diagnosis of P. falciparum malaria (or mixed infections): * in Cohort 1 of ≥500 and \<100,000 parasites/µL asexual P. falciparum parasitemia * in Cohort 2 of ≥100 and \<100,000 parasites/µL asexual P. falciparum parasitemia * either congenital or neonatal * either symptomatic or asymptomatic
Exclusion criteria
1. Head circumference \< - 2 SD z-score in cm following WHO age and sex-specific reference curves (suspicion of microcephaly) 2. Presence of severe malaria (according to WHO 2015 definition) 3. HIV status : * in Cohort 1, patient's or patient's mother's current treatment with ARV * in Cohort 2, mother's known HIV positive status at patient's birth or mother's current treatment with ARV 4. Presence of the following signs of a critical condition: apnea-bradycardia, sustained bradycardia, tachycardia, desaturation, hypotension, hypothermia; or other severely deteriorated general condition (based on IMCI criteria in sick infants) (WHO 2005) 5. Presence of any clinically significant neurological condition: * any episode of convulsion during the present illness (in keeping with the IMCI list of general danger signs) * known neurological disorders (e.g. chronic seizure disorders, cerebral palsy) 6. Presence of clinically significant abnormality of the hepatic and renal systems 7. Patients unable to swallow or whose drinking is impaired 8. Known hypersensitivity of the patient or either patient's parent to artemether, lumefantrine, any of the excipients of Coartem®/Riamet® Dispersible tablet, or to drugs of similar chemical classes 9. History of malabsorption or previous gastrointestinal surgery, or history of radiation therapy that could affect drug absorption or metabolism, or any other disorder or history of a condition that could interfere with drug absorption, distribution, metabolism, or excretion 10. Known family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to be associated with prolongation of the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease 11. Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia) 12. Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities 13. Patients who received any antimalarial drug, including antibiotics with antimalarial activity, within 14 days of trial start, or any other prohibited drug (see Table 6-2) 14. Patients who received an investigational drug within 5 half-lives of enrollment or participated in an investigational study or within 30 days, whichever is longer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Artemether Cmax After First Dose | 1 and 2 hours after first dose (Day 1) | Artemether Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on artemether plasma concentrations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lumefantrine Cmax After Last Dose | 62, 66, 68 and 84 hours after first dose (corresponding to 2, 6, 8 and 24 hours after last dose) | Lumefantrine Cmax represents the highest concentration among four sampling time points after last dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on lumefantrine plasma concentrations. Dosing times were 0, 8, 24, 36, 48 and 60 hours. |
| DHA Cmax After First Dose | 1 and 2 hours after first dose (Day 1) | Dihydroartemisinin (DHA) is an active metabolite of artemether. DHA Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on DHA plasma concentrations. |
| Parasite Clearance Time (PCT) | Up to 48 hours after first dose | PCT is defined as time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours. PCT is based on uncorrected parasite counts. Patients who received rescue medication before parasite clearance were censored at the first use of rescue medication. Patients without parasite clearance were censored at the time of last parasite assessment. PCT was calculated using the Kaplan-Meier method. |
| Fever Clearance Times (FCT) | Up to 36 hours after first dose | FCT is defined as time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours. Patients who received rescue medication before fever clearance were censored at the first use of rescue medication. Patients without fever clearance were censored at the time of last parasite assessment. FCT was calculated using the Kaplan-Meier method. |
| PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis | Days 15, 29 and 43 | PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated on Days 15, 29 and 43. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 15, 29 or 43 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation was considered as a reinfection only if the parasitemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR. |
| Lumefantrine Day 8 Concentration (C168h) | 168 hours after first dose (corresponding to 108 hours after last dose) | Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on lumefantrine plasma concentrations. Dosing times were 0, 8, 24, 36, 48 and 60 hours. |
| PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR) | Days 8, 15, 29 and 43 | PCR-uncorrected ACPR, defined as the absence of parasitemia, was evaluated on Days 8, 15, 29 and 43. A participant was considered as PCR-uncorrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 8, 15, 29 or 43 irrespective of axillary temperature. |
| Number of Participants With Recrudescence Events | Days 15, 29 and 43 | Recrudescence is defined as appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline. Recrudescence had to be confirmed by PCR analysis. |
| Number of Participants With New Infections Events | Days 15, 29 and 43 | New infection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline. New infection had to be confirmed by PCR analysis. |
| Number of Participants With Adverse Events (AEs) | From first dose of study treatment until Day 43 | Number of participants with adverse events (any AEs regardless of seriousness), including changes in laboratory results qualifying and reported as adverse events. |
| Number of Participants With Serious Adverse Events (SAEs) | From first dose of study treatment until 12 months of age (assessed up to maximum 1 year) | Number of participants with serious adverse events (SAEs), including changes in laboratory results qualifying and reported as serious adverse events. |
| PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis | Days 15, 29 and 43 | PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated on Days 15, 29 and 43. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 15, 29 or 43 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation was considered as a reinfection only if the parasitemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR. |
Countries
Burkina Faso, Democratic Republic of the Congo
Participant flow
Recruitment details
Participants took part in 3 investigative sites in 2 countries.
Pre-assignment details
The Screening procedures began once the study informed consent had been obtained. Screening was performed within 12 hours before the first study drug administration.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Infants \>28 days of age treated with artemether-lumefantrine (5 mg:60 mg) twice daily for 3 days | 22 |
| Cohort 2 Term neonates 1-28 days of age treated with artemether-lumefantrine (5 mg:60 mg) twice daily for 3 days | 6 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 96.0 days | 22.5 days | 83.0 days |
| Age, Customized 15-28 days | 0 Participants | 5 Participants | 5 Participants |
| Age, Customized 1-7 days | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized >28 days | 22 Participants | 0 Participants | 22 Participants |
| Age, Customized 8-14 days | 0 Participants | 0 Participants | 0 Participants |
| Plasmodium falciparum density | 8400 parasites/µL | 3660 parasites/µL | 7020 parasites/µL |
| Plasmodium species P. falciparum asexual forms | 21 Participants | 6 Participants | 27 Participants |
| Plasmodium species P. falciparum gametocytes | 4 Participants | 1 Participants | 5 Participants |
| Plasmodium species P. knowlesi | 0 Participants | 0 Participants | 0 Participants |
| Plasmodium species P. malariae | 1 Participants | 0 Participants | 1 Participants |
| Plasmodium species P. ovale | 0 Participants | 0 Participants | 0 Participants |
| Plasmodium species P. vivax | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 22 Participants | 6 Participants | 28 Participants |
| Sex: Female, Male Female | 15 Participants | 3 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 10 Participants |
| Weight | 4.82 kilograms | 3.50 kilograms | 4.76 kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 6 | 0 / 28 |
| other Total, other adverse events | 17 / 22 | 4 / 6 | 21 / 28 |
| serious Total, serious adverse events | 0 / 22 | 0 / 6 | 0 / 28 |
Outcome results
Primary
Artemether Cmax After First Dose
Artemether Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on artemether plasma concentrations.
Time frame: 1 and 2 hours after first dose (Day 1)
Population: Participants in the PK set who had an available value for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1 | Artemether Cmax After First Dose | 68.0 ng/mL |
| Cohort 2 | Artemether Cmax After First Dose | 62.2 ng/mL |
Secondary
DHA Cmax After First Dose
Dihydroartemisinin (DHA) is an active metabolite of artemether. DHA Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on DHA plasma concentrations.
Time frame: 1 and 2 hours after first dose (Day 1)
Population: Participants in the PK set who had an available value for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1 | DHA Cmax After First Dose | 11.5 ng/mL |
| Cohort 2 | DHA Cmax After First Dose | 15.7 ng/mL |
Secondary
Fever Clearance Times (FCT)
FCT is defined as time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours. Patients who received rescue medication before fever clearance were censored at the first use of rescue medication. Patients without fever clearance were censored at the time of last parasite assessment. FCT was calculated using the Kaplan-Meier method.
Time frame: Up to 36 hours after first dose
Population: Participants in the Full Analysis Set (FAS) who had fever at baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Fever Clearance Times (FCT) | 15.7 hours |
| Cohort 2 | Fever Clearance Times (FCT) | 7.6 hours |
Secondary
Lumefantrine Cmax After Last Dose
Lumefantrine Cmax represents the highest concentration among four sampling time points after last dose. Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on lumefantrine plasma concentrations. Dosing times were 0, 8, 24, 36, 48 and 60 hours.
Time frame: 62, 66, 68 and 84 hours after first dose (corresponding to 2, 6, 8 and 24 hours after last dose)
Population: Participants in the PK set who had an available value for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1 | Lumefantrine Cmax After Last Dose | 3180 ng/mL |
| Cohort 2 | Lumefantrine Cmax After Last Dose | 3510 ng/mL |
Secondary
Lumefantrine Day 8 Concentration (C168h)
Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on lumefantrine plasma concentrations. Dosing times were 0, 8, 24, 36, 48 and 60 hours.
Time frame: 168 hours after first dose (corresponding to 108 hours after last dose)
Population: Participants in the PK set who had an available value for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1 | Lumefantrine Day 8 Concentration (C168h) | 353 ng/mL |
| Cohort 2 | Lumefantrine Day 8 Concentration (C168h) | 480 ng/mL |
Secondary
Number of Participants With Adverse Events (AEs)
Number of participants with adverse events (any AEs regardless of seriousness), including changes in laboratory results qualifying and reported as adverse events.
Time frame: From first dose of study treatment until Day 43
Population: Safety Set, including all patients who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Number of Participants With Adverse Events (AEs) | 17 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AEs) | 4 Participants |
Secondary
Number of Participants With New Infections Events
New infection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline. New infection had to be confirmed by PCR analysis.
Time frame: Days 15, 29 and 43
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With New Infections Events | Day 15 | 0 Participants |
| Cohort 1 | Number of Participants With New Infections Events | Day 29 | 4 Participants |
| Cohort 1 | Number of Participants With New Infections Events | Day 43 | 2 Participants |
| Cohort 2 | Number of Participants With New Infections Events | Day 15 | 0 Participants |
| Cohort 2 | Number of Participants With New Infections Events | Day 29 | 0 Participants |
| Cohort 2 | Number of Participants With New Infections Events | Day 43 | 0 Participants |
Secondary
Number of Participants With Recrudescence Events
Recrudescence is defined as appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline. Recrudescence had to be confirmed by PCR analysis.
Time frame: Days 15, 29 and 43
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With Recrudescence Events | Day 15 | 0 Participants |
| Cohort 1 | Number of Participants With Recrudescence Events | Day 29 | 1 Participants |
| Cohort 1 | Number of Participants With Recrudescence Events | Day 43 | 1 Participants |
| Cohort 2 | Number of Participants With Recrudescence Events | Day 15 | 0 Participants |
| Cohort 2 | Number of Participants With Recrudescence Events | Day 29 | 0 Participants |
| Cohort 2 | Number of Participants With Recrudescence Events | Day 43 | 0 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs)
Number of participants with serious adverse events (SAEs), including changes in laboratory results qualifying and reported as serious adverse events.
Time frame: From first dose of study treatment until 12 months of age (assessed up to maximum 1 year)
Population: Safety Set, including all patients who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| Cohort 2 | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Parasite Clearance Time (PCT)
PCT is defined as time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours. PCT is based on uncorrected parasite counts. Patients who received rescue medication before parasite clearance were censored at the first use of rescue medication. Patients without parasite clearance were censored at the time of last parasite assessment. PCT was calculated using the Kaplan-Meier method.
Time frame: Up to 48 hours after first dose
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Parasite Clearance Time (PCT) | 35.0 hours |
| Cohort 2 | Parasite Clearance Time (PCT) | 30.6 hours |
Secondary
PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis
PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated on Days 15, 29 and 43. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 15, 29 or 43 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation was considered as a reinfection only if the parasitemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.
Time frame: Days 15, 29 and 43
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis | Day 15 | 100 percentage of participants |
| Cohort 1 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis | Day 29 | 95.5 percentage of participants |
| Cohort 1 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis | Day 43 | 90.9 percentage of participants |
| Cohort 2 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis | Day 15 | 100 percentage of participants |
| Cohort 2 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis | Day 29 | 100 percentage of participants |
| Cohort 2 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis | Day 43 | 100 percentage of participants |
Secondary
PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis
PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated on Days 15, 29 and 43. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 15, 29 or 43 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation was considered as a reinfection only if the parasitemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.
Time frame: Days 15, 29 and 43
Population: Per-Protocol Set (PPS). Five patients in Cohort 1 were excluded from the PPS due to the use of prohibited concomitant medication, i.e. erythromycin.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis | Day 15 | 100 percentage of participants |
| Cohort 1 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis | Day 29 | 100 percentage of participants |
| Cohort 1 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis | Day 43 | 94.1 percentage of participants |
| Cohort 2 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis | Day 15 | 100 percentage of participants |
| Cohort 2 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis | Day 29 | 100 percentage of participants |
| Cohort 2 | PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis | Day 43 | 100 percentage of participants |
Secondary
PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR)
PCR-uncorrected ACPR, defined as the absence of parasitemia, was evaluated on Days 8, 15, 29 and 43. A participant was considered as PCR-uncorrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 8, 15, 29 or 43 irrespective of axillary temperature.
Time frame: Days 8, 15, 29 and 43
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR) | Day 8 | 100 percentage of participants |
| Cohort 1 | PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR) | Day 15 | 100 percentage of participants |
| Cohort 1 | PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR) | Day 29 | 77.3 percentage of participants |
| Cohort 1 | PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR) | Day 43 | 63.6 percentage of participants |
| Cohort 2 | PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR) | Day 43 | 100 percentage of participants |
| Cohort 2 | PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR) | Day 8 | 100 percentage of participants |
| Cohort 2 | PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR) | Day 29 | 100 percentage of participants |
| Cohort 2 | PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR) | Day 15 | 100 percentage of participants |