Trial Outcomes & Findings for Phase IIa Proof of Concept Study of M5717-Pyronaridine in Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1) (NCT NCT05689047)

NCT ID: NCT05689047

Last Updated: 2025-08-27

Results Overview

An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 38 participants
• Primary outcome timeframe: Day 1 up to Day 43
• Results posted on: 2025-08-27

Participant Flow

Based on the data evaluated in Cohort A and Cohort B0, it was decided not to conduct Cohorts B1, B2 and B3 and study was completed after completion of Cohorts A and B0. Therefore, no enrollment was done in Cohorts B1, B2, and B3. All study analyses were conducted using data from Cohort A and B0 only.

Participant milestones

Measure	Cohort A: M5717+Pyronaridine Participants received 330 milligrams (mg) granules of M5717 orally in combination with 360 mg pyronaridine tablet	Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally in combination with 360 mg pyronaridine daily or adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717 in combination with 540 mg pyronaridine once daily under fasting condition. Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition. The follow up period for participants was 28 days.
Overall Study STARTED	12	26
Overall Study COMPLETED	11	25
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Cohort A: M5717+Pyronaridine Participants received 330 milligrams (mg) granules of M5717 orally in combination with 360 mg pyronaridine tablet	Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally in combination with 360 mg pyronaridine daily or adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717 in combination with 540 mg pyronaridine once daily under fasting condition. Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition. The follow up period for participants was 28 days.
Overall Study Lost to Follow-up	0	1
Overall Study Protocol Deviation	1	0

Baseline Characteristics

Phase IIa Proof of Concept Study of M5717-Pyronaridine in Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)

Baseline characteristics by cohort

Measure	Cohort A: M5717+Pyronaridine n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally in combination with 360 mg pyronaridine tablet	Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine n=26 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally in combination with 360 mg pyronaridine daily or adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717 in combination with 540 mg pyronaridine once daily under fasting condition. Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition. The follow up period for participants was 28 days.	Total n=38 Participants Total of all reporting groups
Age, Continuous	23 Years STANDARD_DEVIATION 9.56 • n=93 Participants	18 Years STANDARD_DEVIATION 9.03 • n=4 Participants	20 Years STANDARD_DEVIATION 9.38 • n=27 Participants
Sex: Female, Male Female	11 Participants n=93 Participants	15 Participants n=4 Participants	26 Participants n=27 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	11 Participants n=4 Participants	12 Participants n=27 Participants
Race/Ethnicity, Customized Ethnicity-Hispanic or Latino	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino	0 Participants n=93 Participants	25 Participants n=4 Participants	25 Participants n=27 Participants
Race/Ethnicity, Customized Ethnicity-Unknown or Not Reported	12 Participants n=93 Participants	0 Participants n=4 Participants	12 Participants n=27 Participants
Race/Ethnicity, Customized Race-Black or African American	12 Participants n=93 Participants	25 Participants n=4 Participants	37 Participants n=27 Participants
Race/Ethnicity, Customized Race-White	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants

PRIMARY outcome

Timeframe: Day 1 up to Day 43

Population: The safety analysis set included all participants, who were administered any dose of any study intervention.

An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs TEAEs	—	—	9 Participants	—	—	—
Cohort A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs Serious TEAEs	—	—	0 Participants	—	—	—
Cohort A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs Related TEAEs	—	—	1 Participants	—	—	—

PRIMARY outcome

Timeframe: Day 1 up to Day 29

Population: The safety analysis set included all participants, who were administered any dose of any study intervention.

Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, and coagulation.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A: Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters	—	—	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Day 1 up to Day 29

Population: The safety analysis set included all participants, who were administered any dose of any study intervention.

Number of participants with clinically significant change from baseline in ECG parameters were reported. Clinical Significance was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A: Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings	—	—	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Day 1 up to Day 29

Population: The safety analysis set included all participants, who were administered any dose of any study intervention.

Number of participants with clinically significant change from baseline in vital signs. Clinical Significance was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A: Number of Participants With Clinically Significant Change From Baseline in Vital Signs	—	—	0 Participants	—	—	—

PRIMARY outcome

Timeframe: At Day 29

Population: The Full Analysis Set included all enrolled participants. ACPR could not be assessed for 1 participant due to missing parasites assessment at Day 28. Here "Number Analyzed" is equivalent to the number of participants evaluable for this outcome measure.

PCR-adjusted ACPR 28 days after first treatment (i.e., on Day 29) was defined as absence of parasitemia (thick smear/microscopy, after adjustment for parasitemia due to new infections as determined by genotyping using PCR techniques), irrespective of axillary temperature, in participants who did not previously meet any of the criteria of Early treatment failure (ETF), Late clinical failure (LCF), or Late parasitological failure (LPF).

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=24 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort B0: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR)	—	—	92.3 percentage of participants Interval 75.9 to 97.9	—	—	—

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The Pharmacokinetics (PK) analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide more than equal to (\>=) 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination. Calculated as AUC0-inf = AUC0-tlast + Clast pred/ lambda z.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 and Pyronaridine	8557.596 hour*nanogram/milliliter(h*ng/ml) Geometric Coefficient of Variation 0.347	5899.378 hour*nanogram/milliliter(h*ng/ml) Geometric Coefficient of Variation 0.289	11194.723 hour*nanogram/milliliter(h*ng/ml) Geometric Coefficient of Variation 0.238	33307.278 hour*nanogram/milliliter(h*ng/ml) Geometric Coefficient of Variation 0.153	33756.087 hour*nanogram/milliliter(h*ng/ml) Geometric Coefficient of Variation 0.384	4397.819 hour*nanogram/milliliter(h*ng/ml) Geometric Coefficient of Variation 0.590

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

The AUC from time zero (dosing time) to 24 hours post dose was calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M5717 and Pyronaridine	2113.426 h*ng/ml Geometric Coefficient of Variation 0.399	1603.917 h*ng/ml Geometric Coefficient of Variation 0.197	3663.092 h*ng/ml Geometric Coefficient of Variation 0.373	13063.782 h*ng/ml Geometric Coefficient of Variation 0.127	12038.002 h*ng/ml Geometric Coefficient of Variation 0.393	1206.579 h*ng/ml Geometric Coefficient of Variation 0.417

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

The AUC from time zero (= dosing time) to the time of the last quantifiable concentration (tlast), calculated using the mixed log linear trapezoidal rule (linear up, log down)

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) of M5717 and Pyronaridine	8557.596 h*ng/ml Geometric Coefficient of Variation 0.347	5899.378 h*ng/ml Geometric Coefficient of Variation 0.289	9877.195 h*ng/ml Geometric Coefficient of Variation 0.455	32747.057 h*ng/ml Geometric Coefficient of Variation 0.153	33275.071 h*ng/ml Geometric Coefficient of Variation 0.391	4397.819 h*ng/ml Geometric Coefficient of Variation 0.590

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

The apparent total body clearance of study intervention following extravascular administration. CL/ F was calculated by oral dose divided by Area under the plasma concentration curve 0- infinity.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Apparent Total Clearance (CL/F) of M5717 and Pyronaridine	63.102 Liters/hour (l/h) Geometric Coefficient of Variation 0.347	122.047 Liters/hour (l/h) Geometric Coefficient of Variation 0.289	29.478 Liters/hour (l/h) Geometric Coefficient of Variation 0.238	15.012 Liters/hour (l/h) Geometric Coefficient of Variation 0.153	19.552 Liters/hour (l/h) Geometric Coefficient of Variation 0.384	81.859 Liters/hour (l/h) Geometric Coefficient of Variation 0.590

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

Cmax was taken directly from the observed concentration-time curve.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Maximum Plasma Concentration (Cmax) of M5717 and Pyronaridine	191.000 ng/ml Geometric Coefficient of Variation 78.773	138.000 ng/ml Geometric Coefficient of Variation 15.122	269.358 ng/ml Geometric Coefficient of Variation 0.483	956.145 ng/ml Geometric Coefficient of Variation 0.173	991.144 ng/ml Geometric Coefficient of Variation 0.385	125.600 ng/ml Geometric Coefficient of Variation 44.565

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

t1/2 was the time measured for the concentration to decrease by one half. t1/2 was calculated by natural log 2 divided by Lambda z.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Apparent Terminal Half-Life of M5717 and Pyronaridine	228.509 hours (h) Geometric Coefficient of Variation 0.233	229.264 hours (h) Geometric Coefficient of Variation 0.314	74.523 hours (h) Geometric Coefficient of Variation 0.264	65.638 hours (h) Geometric Coefficient of Variation 0.152	84.202 hours (h) Geometric Coefficient of Variation 0.325	174.918 hours (h) Geometric Coefficient of Variation 0.599

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

tmax was obtained directly from the concentration versus time curve.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Time to Reach Maximum Plasma Concentration (Tmax) of M5717 and Pyronaridine	3.394 hours Geometric Coefficient of Variation 0.599	4.444 hours Geometric Coefficient of Variation 0.767	3.179 hours Geometric Coefficient of Variation 0.480	2.784 hours Geometric Coefficient of Variation 0.385	3.196 hours Geometric Coefficient of Variation 0.508	2.778 hours Geometric Coefficient of Variation 0.325

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

The apparent volume of distribution during the terminal phase following extravascular administration. Vz/F = Dose/(AUC0-∞*λz) following single dose.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Apparent Volume of Distribution (Vz/F) of M5717 and Pyronaridine	20802.718 liters (l) Geometric Coefficient of Variation 0.250	40368.007 liters (l) Geometric Coefficient of Variation 0.224	3169.306 liters (l) Geometric Coefficient of Variation 0.389	1421.536 liters (l) Geometric Coefficient of Variation 0.220	2375.135 liters (l) Geometric Coefficient of Variation 0.647	20657.284 liters (l) Geometric Coefficient of Variation 0.459

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

The dose normalized AUC from time zero to 24 hours post dose. Normalized using the dose, using the formula AUC0-24/Dose.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Dose Normalized Area Under the Curve From Time Zero to 24 Hours Post Dose (AUC0-24h/Dose) of M5717 and Pyronaridine	3.914 h*ng/mL/mg Geometric Coefficient of Variation 0.399	2.228 h*ng/mL/mg Geometric Coefficient of Variation 0.197	11.100 h*ng/mL/mg Geometric Coefficient of Variation 0.373	26.128 h*ng/mL/mg Geometric Coefficient of Variation 0.127	18.239 h*ng/mL/mg Geometric Coefficient of Variation 0.393	3.352 h*ng/mL/mg Geometric Coefficient of Variation 0.417

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

The dose normalized AUC from time zero to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Normalized using the dose, using the formula AUC0-tlast /Dose.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Dose Normalized Area Under the Curve From Time Zero to the Last Sampling Time (AUC0-tlast/Dose) of M5717 and Pyronaridine	14.792 h*ng/mL/mg Geometric Coefficient of Variation 0.366	7.639 h*ng/mL/mg Geometric Coefficient of Variation 0.303	29.931 h*ng/mL/mg Geometric Coefficient of Variation 0.455	65.494 h*ng/mL/mg Geometric Coefficient of Variation 0.153	50.417 h*ng/mL/mg Geometric Coefficient of Variation 0.391	11.033 h*ng/mL/mg Geometric Coefficient of Variation 0.625

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

The dose normalized AUC from time zero extrapolated to infinity. Normalized using dose, using the formula AUC0-∞ /Dose.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Dose Normalized Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞/Dose) of M5717 and Pyronaridine	15.847 h*ng/mL/mg Geometric Coefficient of Variation 0.347	8.194 h*ng/mL/mg Geometric Coefficient of Variation 0.289	33.923 h*ng/mL/mg Geometric Coefficient of Variation 0.238	66.615 h*ng/mL/mg Geometric Coefficient of Variation 0.153	51.146 h*ng/mL/mg Geometric Coefficient of Variation 0.384	12.216 h*ng/mL/mg Geometric Coefficient of Variation 0.590

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Terminal Elimination Rate Constant (Lambda z) of M5717 and Pyronaridine	0.003 hours (h) Geometric Coefficient of Variation 0.233	0.003 hours (h) Geometric Coefficient of Variation 0.314	0.009 hours (h) Geometric Coefficient of Variation 0.264	0.011 hours (h) Geometric Coefficient of Variation 0.152	0.008 hours (h) Geometric Coefficient of Variation 0.325	0.004 hours (h) Geometric Coefficient of Variation 0.599

SECONDARY outcome

Timeframe: Predose and Post dose on Day 1, Post dose on Day 2, 3, 4, 8, 15, 22, 29 and Day 43

Population: The PK analysis set included all participants, who received more than equal to 1 dose of study intervention, have no clinically important protocol deviations or important events affecting PK and provide \>= 1 measurable post-dose concentration. Dose wise results have been reported for M5717 and Pyronaridine as per the planned analysis.

The dose normalized maximum concentration. Normalized using the dose, and the formula Cmax /Dose.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg n=11 Participants Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg n=4 Participants Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg n=15 Participants Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg n=21 Participants Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Dose Normalized Maximum Concentration (Cmax/Dose) of M5717 and Pyronaridine	15.847 ng/mL/mg Geometric Coefficient of Variation 0.347	8.194 ng/mL/mg Geometric Coefficient of Variation 0.289	0.816 ng/mL/mg Geometric Coefficient of Variation 0.483	1.912 ng/mL/mg Geometric Coefficient of Variation 0.173	1.502 ng/mL/mg Geometric Coefficient of Variation 0.385	12.216 ng/mL/mg Geometric Coefficient of Variation 0.590

SECONDARY outcome

Timeframe: Up to Day 3 post treatment on Day 1

Population: The Full Analysis Set (FAS) included all enrolled participants.

Early treatment failure (ETF) was defined as meeting any of the following : 1. Danger signs or severe malaria 1, 2, or 3 days after treatment, in the presence of parasitemia2. Parasitemia 2 days after treatment higher than on day of treatment, irrespective of axillary temperature

• Parasitemia 3 days after treatment with temperature ≥ 37.5°C 3. Parasitemia 3 days after treatment ≥ 25% of count on day of treatment. ETF rate will be estimated with 95% confidence intervals. Confidence intervals was derived by use of Wilson's score method.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=26 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Percentage of Participants With Early Treatment Failure (ETF)	—	—	0.0 percentage of participants Interval 0.0 to 24.3	0.0 percentage of participants Interval 0.0 to 12.9	—	—

SECONDARY outcome

Timeframe: Day 1 up to Day 29

Population: The FAS included all enrolled participants.

Late clinical failure (LCF) was defined as:1. Danger signs or severe malaria in the presence of parasitemia on any day between 4 and 28 days after treatment (i.e., between Days 5 and 29) in participants who did not previously meet any of the criteria of ETF. 2. Presence of parasitemia on any day between 4 and 28 days after treatment with temperature ≥ 37.5°C in participants who did not previously meet any of the criteria of ETF. LCF was estimated with 95% confidence intervals. Confidence intervals will be derived by use of Wilson's score method.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=26 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Percentage of Participants With Late Clinical Failure (LCF)	—	—	0.0 percentage of participants Interval 0.0 to 24.3	0.0 percentage of participants Interval 0.0 to 12.9	—	—

SECONDARY outcome

Timeframe: From Day 8 to Day 29

Population: The FAS included all enrolled participants.

Late parasitological failure (LPF) was defined as: Presence of parasitemia on any day between 7 and 28 days after treatment (i.e., between Days 8 and 29) with temperature < 37.5°C in participants who did not previously meet any of the criteria of ETF or LCF. LPF was estimated with 95% confidence intervals. Confidence intervals will be derived by use of Wilson's score method.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=26 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Percentage of Participants With Late Parasitological Failure (LPF)	—	—	0.0 percentage of participants Interval 0.0 to 24.3	0.0 percentage of participants Interval 0.0 to 12.9	—	—

SECONDARY outcome

Timeframe: Day 28 and 42

Population: The FAS included all enrolled participants. ACPR could not be assessed for 1 patient due to missing parasites assessment at Day 28.

PCR-adjusted ACPR 28 and 42 days after treatment defined as absence of parasitemia (thick smear/microscopy, after adjustment for parasitemia due to new infections as determined by genotyping using PCR techniques), irrespective of axillary temperature, in participants who did not previously meet any of the criteria of ETF, LCF, or LPF.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) Day 28	—	—	91.7 percentage of participants Interval 64.6 to 98.5	—	—	—
Cohort A: Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) Day 42	—	—	91.7 percentage of participants Interval 64.6 to 98.5	—	—	—

SECONDARY outcome

Timeframe: Day 28 and 42

Population: The FAS included all enrolled participants.

Crude ACPR 28 and 42 days after first dose is defined as absence of parasitemia (parasite count = 0) from thick smear/microscopy, irrespective of axillary temperature, in participants who did not previously meet any of the criteria of ETF, LCF, or LPF.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=26 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and B0: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR) Day 28	—	—	91.7 percentage of participants Interval 64.6 to 98.5	92.3 percentage of participants Interval 75.9 to 97.9	—	—
Cohort A and B0: Percentage of Participants With Crude Adequate Clinical and Parasitological Response (ACPR) Day 42	—	—	91.7 percentage of participants Interval 64.6 to 98.5	76.9 percentage of participants Interval 57.9 to 89.0	—	—

SECONDARY outcome

Timeframe: Day 1 up to Day 29

Population: The FAS included all enrolled participants. Here "Number Analyzed" is equivalent to the number of participants evaluable for this outcome measure.

Fever clearance time was defined as the time from first dosing to the first measurement of temperature < 37.5°C for 2 consecutive temperature readings plus confirmed normal temperature 24 h after the first normal body temperature reading. This analysis was done on participants with fever.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=1 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=9 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Time to Fever Clearance as Estimated by Kaplan-Meier Method	—	—	6.0 hours Interval 6.0 to 6.0	6.2 hours Interval 6.0 to 17.9	—	—

SECONDARY outcome

Timeframe: Day 1 up to Day 43

Population: The FAS included all enrolled participants.

Parasite clearance time defined as time from dosing to the first negative (no parasites) film

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=12 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg n=26 Participants Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort A and Cohort B0: Parasite Clearance Time as Estimated by Kaplan-Meier Method	—	—	4.0 days Interval 3.0 to 9.0	4.5 days Interval 2.0 to 10.0	—	—

SECONDARY outcome

Timeframe: Day 1 up to Day 43

Population: The safety analysis set included all participants, who were administered any dose of any study intervention.

An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.

Outcome measures

Measure	Cohort B0: Pyronaridine 540 mg Participants with weight \>=45 to \<65 kg received 540 mg of Pyronaridine tablets under fasting conditions.	Cohort B0: Pyronaridine 720 mg Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets under fasting conditions.	Cohort A: M5717 330 mg n=26 Participants Participants received 330 milligrams (mg) granules of M5717 orally.	Cohort B0: M5717 500 mg Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally.	Cohort B0: M5717 660 mg Adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717.	Cohort A and B0: Pyronaridine 360 mg Participants received 360 mg of pyronaridine tablets under fasting conditions.
Cohort B0: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs TEAEs	—	—	16 Participants	—	—	—
Cohort B0: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs Serious TEAEs	—	—	0 Participants	—	—	—
Cohort B0: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs Related TEAEs	—	—	0 Participants	—	—	—

Adverse Events

Cohort A: M5717+Pyronaridine

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Cohort A: M5717+Pyronaridine n=12 participants at risk Participants received 330 milligrams (mg) granules of M5717 orally in combination with 360 mg pyronaridine tablet	Cohort B0: Dose Escalation Cohort: M5717+Pyronaridine n=26 participants at risk Participants with weight less than (\<) 45 kilograms (kg) received 500 mg granules of M5717 orally in combination with 360 mg pyronaridine daily or adult and adolescent participants with weight more than or equal to (\>=) 45 kg received orally 660 mg granules of M5717 in combination with 540 mg pyronaridine once daily under fasting condition. Participants with weight \>=65 kg received 720 mg of Pyronaridine tablets in combination with M5717 under fasting condition. The follow up period for participants was 28 days.
Blood and lymphatic system disorders Anaemia	0.00% 0/12 • Up to Day 43	11.5% 3/26 • Number of events 3 • Up to Day 43
Infections and infestations Conjunctivitis viral	0.00% 0/12 • Up to Day 43	7.7% 2/26 • Number of events 2 • Up to Day 43
Infections and infestations Malaria	0.00% 0/12 • Up to Day 43	15.4% 4/26 • Number of events 4 • Up to Day 43
Infections and infestations Upper respiratory tract infection	8.3% 1/12 • Number of events 1 • Up to Day 43	11.5% 3/26 • Number of events 3 • Up to Day 43
Infections and infestations Urinary tract infection	16.7% 2/12 • Number of events 2 • Up to Day 43	3.8% 1/26 • Number of events 1 • Up to Day 43
Investigations Blood alkaline phosphatase increased	0.00% 0/12 • Up to Day 43	19.2% 5/26 • Number of events 5 • Up to Day 43
Investigations Blood bilirubin increased	0.00% 0/12 • Up to Day 43	7.7% 2/26 • Number of events 2 • Up to Day 43
Nervous system disorders Dizziness	16.7% 2/12 • Number of events 2 • Up to Day 43	0.00% 0/26 • Up to Day 43
Nervous system disorders Headache	41.7% 5/12 • Number of events 5 • Up to Day 43	3.8% 1/26 • Number of events 1 • Up to Day 43

Additional Information

Communication Center

Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: service@emdgroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place