Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria

A Randomized, Open Label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 Dose Levels of Artefenomel (OZ439) Given in Combination With Ferroquine (FQ) and FQ Alone, in African Patients With Uncomplicated Plasmodium Falciparum Malaria

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03660839

Enrollment

140

Registered

2018-09-07

Start date

2018-09-11

Completion date

2019-11-06

Last updated

2022-03-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Plasmodium Falciparum Infection

Brief summary

Primary Objective: To show the contribution of artefenomel (OZ439) to the clinical and parasiticidal effect of OZ439/Ferroquine (FQ) combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the curve (AUC) of OZ439 as pharmacokinetic (PK) predictor. Secondary Objectives: * To evaluate the exposure-response of OZ439 combined with FQ on crude Day 28 ACPR. * To evaluate the dose response of OZ439 combined with FQ on PCR-corrected and crude Day 28 ACPR. * To evaluate the dose-response of OZ439 combined with FQ on selected secondary endpoints. * To evaluate the safety and tolerability of different dosages of OZ439 in combination with FQ and FQ alone. * To characterize the PK of OZ439 in plasma, and of FQ and its active metabolite SSR97213 in blood.

Detailed description

The duration of the study was up to 32 days, including up to 1 day screening period before the single-dose treatment, 5 days of post-treatment surveillance (included 2 to 4 days hospitalization) and 24±2 days follow-up period.

Interventions

DRUGArtefenomel (OZ439)

Pharmaceutical form: Granules for oral suspension Route of administration: Oral

DRUGFerroquine (SSR97193)

Pharmaceutical form: Capsule Route of administration: Oral

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

14 Years to 69 Years

Healthy volunteers

Inclusion criteria

: Participants (14-69 years old inclusive) with body weight within 35 and 90 kilograms (kg), with uncomplicated Plasmodium falciparum (P. falciparum) malaria, with a fever as defined with axillary temperature greater than or equal to (\>=) 37.5 degree Celsius (°C) or oral/ rectal/ tympanic temperature \>=38°C or history of fever in the previous 24 hours (history of fever was documented), with a mono-infection with P. falciparum and parasitemia (microscopically, blood smear) \>= 3,000 and less than or equal to (\<=) 50,000 asexual parasites per microliter of blood.

Exclusion criteria

* Presence of severe malaria. * Known history or evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, respiratory, endocrine, immunological, infectious, neurological (in particular convulsions), malignancy, psychiatric disease or symptoms which, in the judgment of the investigator, might confuse the interpretation of the safety information. * Severe vomiting defined as more than 3 times in the 24 hours prior to enrollment in the study or inability to tolerate oral treatment or severe diarrhea defined as 3 or more watery stools per day. * Severe malnutrition defined as a body mass index of less than 16 kg per meter square for adults and for children Z-score less than (\<) -3 or weight for age (%) of the median \<60. * Splenectomized participants or presence of surgical scar on left hypochondrium. * Known history of hypersensitivity, allergic, or anaphylactoid reactions to FQ or other amino quinolines or to OZ439 or OZ277 or any of the excipients. * Participant treated with anti-malarial treatment: * With piperaquine phosphate-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine within the previous 6 weeks. * With amodiaquine or chloroquine within the previous 4 weeks. * With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days. * With any herbal products or traditional medicines, within the past 7 days. * Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest, which were: strong Cytochrome P450 (CYP) 2C or CYP3A inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers. * Any treatment known to induce a prolongation of QT interval. * Participated in any trial investigating OZ439 and/or FQ compounds. * Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance. * Enrolled in another clinical trial within the past 4 weeks or during the study period. * Mixed Plasmodium infection. * Presence of Hepatitis A - immunoglobulin, Hepatitis B surface antigen or Hepatitis C virus antibody and/or known to had active Hepatitis C virus ribonucleic acid. * Laboratory parameters with abnormalities deemed clinically significant by the investigator. * Abnormal Liver Function Test: aspartate transferase greater than (\>) 2 upper limit of normal range (ULN), or alanine transferase \>2 ULN or total bilirubin \>1.5 ULN. * Positive pregnancy test at study screening for female participants of childbearing potential. * QT interval corrected using Fridericia formula (QTcF) \>450 milliseconds at screening or pre-dose. * Hypokalemia (\<3.5 millimoles per liter \[mmol/L\]), hypocalcemia (\<2.0 mmol/L) or hypomagnesemia (\<0.5 mmol/L) at screening or pre-dose. * Family history of sudden death or of congenital prolongation of the QT interval or known congenital prolongation of the QT-interval or any clinical condition known to prolong the QT interval e.g., participants with a history of symptomatic cardiac arrhythmias including atrial fibrillation or with clinically relevant bradycardia. * Participant not suitable for participation, whatever the reason, as judged by the Investigator, included medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures or unable to drink. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)	Day 28	ACPR:absence of parasitemia at Day 28, irrespective of axillary temperature(AT), participants not meeting any criteria of early therapy failure(ETF):Danger signs(DS)/symptoms of complicated(SoC)/severe malaria(SM) at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia;or parasitemia on Day 2 \>Day 0 irrespective of AT;or parasitemia on Day 3 with AT\>=37.5 degree Celsius (°C);or parasitemia count on Day 3 \>=25 percent (%) on Day 0, or late clinical failure (LCF):DS/SM in presence of parasitemia between Day 4 and 28,concomitant to at least one positive parasitemia;or presence of parasitemia and AT\>=37.5°C on Day 4 to Day 28, or late parasitological failure(LPF):presence of parasitemia between Day 7 and 28 and AT\<37.5°C and without rescue therapy. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with reinfection.

Secondary

Measure	Time frame	Description
Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Baseline, 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post-dose	Parasitemia (quantitative content of parasites present in the blood) at baseline until Day 7 (i.e. 168 hours) was assessed by optical microscope.
Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	Baseline, 24, 48 and 72 hours post-dose	The observed PRR was defined as the ratio of the number of parasites at time t=0 (baseline) divided by the parasite count at each specified time t (post-treatment). If the post dose parasite count = 0 (due to a negative parasitemia) then a value of 1 parasite per microliter was imputed to allow a parasite reduction ratio calculation.
Time to 50% and 99% Parasite Reduction	Up to Day 28	Time to 50% and 99% parasite reduction was defined as time needed for the parasitemia (quantitative content of parasites present in blood) to be reduced to 50% and 99% of the initial value, respectively.
Parasite Clearance Time (PCT)	From the start of study drug administration up to the time of the first negative blood film (up to Day 28)	PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites by microscopy). This first negative film was confirmed by a second negative film which was taken \>=6 to \<=12 hours of the first film. If the second film was performed \<6 hours or \>12 hours of the first film, then the parasite clearance was confirmed or invalidated by the third (thick) film following the second one, whatever the timing of this third film: If the third film was negative, then the clearance was considered confirmed and if the third film was positive, then the clearance was invalidated. Kaplan-Meier method was used for the estimation.
Parasite Clearance Rate	Up to Day 28	Parasite clearance rate (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite Clearance Estimator.
Time to Re-emergence	Up to Day 28	Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Re-emergence was confirmed by microscopy (positive blood smear). Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation.
Time to Recrudescence	Up to Day 28	Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation.
Time to Re-infection	Up to Day 28	Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differed from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Maier method was used for estimation.
Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia	Up to Day 28	The time elapsed below LOQ (LOQ expressed in parasites/microliter) of parasitemia (quantitative content of parasites present in the blood) was defined as the time (in days) for which no parasites were seen i.e., time corresponding to PCT, up to the time of occurrence of a new malaria infection or recrudescence. If there was no occurrence of a new malaria infection or recrudescence, then this was the time corresponding to the first negative thick blood film, until the end of study. PCT (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite clearance estimator. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Meier method was used for estimation.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	From Baseline up to Day 28	An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to the Day 28. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.
Pharmacokinetics (PK): Concentration of OZ439 in Plasma	1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose	Concentrations of OZ439 in plasma was analyzed by liquid chromatography tandem mass spectroscopy (LC-MS/MS). The lower limit of quantification (LLOQ) was 1 nanograms per milliliter for analysis of OZ439. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28	Day 28	ACPR: absence of parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS/SoC/SM at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia; or parasitemia on Day 2 \> Day 0 irrespective of AT; or parasitemia on Day 3 with AT \>=37.5°C; or parasitemia count on Day 3 \>=25% on Day 0, or LCF: DS/SM in presence of parasitemia between Day 4 and 28, concomitant to at least one positive parasitemia; or presence of parasitemia and AT\>=37.5°C on Day 4 to Day 28, or LPF: presence of parasitemia between Day 7 and 28 and AT\<37.5°C or having rescue therapy for malaria. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish reinfection (new clone of parasite) or recrudescence.
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel	Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose	Cmax is the maximum observed plasma concentration of Artefenomel. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.
Pharmacokinetics: Time to Reach Maximum Plasma Concentration (Tmax) of Artefenomel	Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose	tmax is the time taken by the drug to reach the maximum plasma concentration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.
Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel	At 168 hours post-dose	The observed plasma concentration of artefenomel post 168 hours of drug administration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.
Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel	Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose	Area under the plasma concentration versus time curve from time 0 to infinity. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.
Pharmacokinetics: Terminal Half-life (t1/2) of Artefenomel	Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose	Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.
Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose	Cmax is the maximum observed plasma concentration of Ferroquine.
Pharmacokinetics: Time to Reach Maximum Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose	tmax is the time taken by the drug to reach the maximum plasma concentration.
Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213	At 168 hours post-dose	The observed plasma concentration of FQ and SSR97213 post 168 hours of FQ administration.
Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213	Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose	Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours).
Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213	Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose	Area under the plasma concentration versus time curve from time 0 to infinity.
Pharmacokinetics: Terminal Half-life of Ferroquine	Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose	Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration.
Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose	Concentrations of FQ and SSR97213 in blood was analyzed by LC-MS/MS. The LLOQ was 5 nanograms per milliliter for analysis of FQ and SSR97213.

Countries

Benin, Burkina Faso, Gabon, Kenya, Uganda

Participant flow

Recruitment details

Study was conducted at 7 active sites in 5 countries. Total of 448 participants were screened between 11 September 2018 and 09 October 2019, of which 140 were randomized to 1 of 4 treatment arms and those who failed to meet inclusion criteria were considered as screen failure.

Pre-assignment details

All eligible participants were randomized via a centralized randomization system using interactive response technology to 1 of the 4 arms in 1:1:1:1 ratio. Day 0 (drug administration day, per protocol) was considered as Day 1 for all analysis using Safety population as per Clinical Data Interchange Standards Consortium convention.

Participants by arm

Arm	Count
Ferroquine 400 mg On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	35
Ferroquine 400 mg + Artefenomel 300 mg On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 300 mg oral suspension.	36
Ferroquine 400 mg + Artefenomel 600 mg On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 600 mg oral suspension.	36
Ferroquine 400 mg + Artefenomel 1000 mg On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition followed by OZ439 1000 mg oral suspension.	33
Total	140

Baseline characteristics

Characteristic	Ferroquine 400 mg	Total	Ferroquine 400 mg + Artefenomel 1000 mg	Ferroquine 400 mg + Artefenomel 600 mg	Ferroquine 400 mg + Artefenomel 300 mg
Age, Continuous	25.4 years STANDARD_DEVIATION 13.2	22.5 years STANDARD_DEVIATION 11.26	22.2 years STANDARD_DEVIATION 11.28	20.7 years STANDARD_DEVIATION 8.57	21.8 years STANDARD_DEVIATION 11.49
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	35 Participants	139 Participants	33 Participants	35 Participants	36 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Race (NIH/OMB) White	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Female	23 Participants	97 Participants	20 Participants	26 Participants	28 Participants
Sex: Female, Male Male	12 Participants	43 Participants	13 Participants	10 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 35	0 / 36	0 / 36	0 / 33
other Total, other adverse events	13 / 35	17 / 36	17 / 36	22 / 33
serious Total, serious adverse events	0 / 35	0 / 36	1 / 36	0 / 33

Outcome results

Primary

Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)

ACPR:absence of parasitemia at Day 28, irrespective of axillary temperature(AT), participants not meeting any criteria of early therapy failure(ETF):Danger signs(DS)/symptoms of complicated(SoC)/severe malaria(SM) at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia;or parasitemia on Day 2 \>Day 0 irrespective of AT;or parasitemia on Day 3 with AT\>=37.5 degree Celsius (°C);or parasitemia count on Day 3 \>=25 percent (%) on Day 0, or late clinical failure (LCF):DS/SM in presence of parasitemia between Day 4 and 28,concomitant to at least one positive parasitemia;or presence of parasitemia and AT\>=37.5°C on Day 4 to Day 28, or late parasitological failure(LPF):presence of parasitemia between Day 7 and 28 and AT\<37.5°C and without rescue therapy. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with reinfection.

Time frame: Day 28

Population: Pharmacokinetic/Pharmacodynamic (PK/PD) efficacy population: who received at least 1 dose of OZ439/FQ with parasitologically confirmed Plasmodium falciparum at baseline with data post-randomization, 1 evaluable PK blood sample (OZ439/FQ) post dose, adequate documentation of dosing \& sampling date, without any major protocol deviation related to drug administration (e.g. vomiting after drug intake). Here,overall number of participants analyzed=participants evaluable for this outcome measure.

Arm	Measure	Value (NUMBER)
Ferroquine 400 mg	Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)	80.8 percentage of participants
Ferroquine 400 mg + Artefenomel 300 mg	Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)	90.3 percentage of participants
Ferroquine 400 mg + Artefenomel 600 mg	Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)	90.9 percentage of participants
Ferroquine 400 mg + Artefenomel 1000 mg	Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)	87.1 percentage of participants

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)

An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to the Day 28. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.

Time frame: From Baseline up to Day 28

Population: Analysis was performed on safety population: participants who received single administration of OZ439/FQ and were analyzed according to the treatment actually received.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Ferroquine 400 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE	18 Participants
Ferroquine 400 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any treatment-emergent AESI	0 Participants
Ferroquine 400 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE led to treatment discontinuation	0 Participants
Ferroquine 400 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE led to death	0 Participants
Ferroquine 400 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any treatment-emergent SAE	0 Participants
Ferroquine 400 mg + Artefenomel 300 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any treatment-emergent AESI	1 Participants
Ferroquine 400 mg + Artefenomel 300 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any treatment-emergent SAE	0 Participants
Ferroquine 400 mg + Artefenomel 300 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE led to death	0 Participants
Ferroquine 400 mg + Artefenomel 300 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE	21 Participants
Ferroquine 400 mg + Artefenomel 300 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE led to treatment discontinuation	0 Participants
Ferroquine 400 mg + Artefenomel 600 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE led to treatment discontinuation	0 Participants
Ferroquine 400 mg + Artefenomel 600 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE led to death	0 Participants
Ferroquine 400 mg + Artefenomel 600 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any treatment-emergent SAE	1 Participants
Ferroquine 400 mg + Artefenomel 600 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE	24 Participants
Ferroquine 400 mg + Artefenomel 600 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any treatment-emergent AESI	0 Participants
Ferroquine 400 mg + Artefenomel 1000 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any treatment-emergent AESI	1 Participants
Ferroquine 400 mg + Artefenomel 1000 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE led to treatment discontinuation	0 Participants
Ferroquine 400 mg + Artefenomel 1000 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE	24 Participants
Ferroquine 400 mg + Artefenomel 1000 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any treatment-emergent SAE	0 Participants
Ferroquine 400 mg + Artefenomel 1000 mg	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)	Any TEAE led to death	0 Participants

Secondary

Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours

The observed PRR was defined as the ratio of the number of parasites at time t=0 (baseline) divided by the parasite count at each specified time t (post-treatment). If the post dose parasite count = 0 (due to a negative parasitemia) then a value of 1 parasite per microliter was imputed to allow a parasite reduction ratio calculation.

Time frame: Baseline, 24, 48 and 72 hours post-dose

Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category.

Arm	Measure	Group	Value (MEAN)	Dispersion
Ferroquine 400 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 72	15655.447 ratio	Standard Deviation 12806.4644
Ferroquine 400 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 48	9709.093 ratio	Standard Deviation 13987.7127
Ferroquine 400 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 24	638.436 ratio	Standard Deviation 2013.8609
Ferroquine 400 mg + Artefenomel 300 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 24	5921.197 ratio	Standard Deviation 11566.152
Ferroquine 400 mg + Artefenomel 300 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 72	18069.583 ratio	Standard Deviation 13409.1341
Ferroquine 400 mg + Artefenomel 300 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 48	17594.700 ratio	Standard Deviation 13521.9507
Ferroquine 400 mg + Artefenomel 600 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 72	14561.409 ratio	Standard Deviation 13657.0665
Ferroquine 400 mg + Artefenomel 600 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 24	5715.046 ratio	Standard Deviation 9364.8892
Ferroquine 400 mg + Artefenomel 600 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 48	13120.409 ratio	Standard Deviation 13182.3022
Ferroquine 400 mg + Artefenomel 1000 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 24	7929.720 ratio	Standard Deviation 12675.8348
Ferroquine 400 mg + Artefenomel 1000 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 48	19328.057 ratio	Standard Deviation 14392.7604
Ferroquine 400 mg + Artefenomel 1000 mg	Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours	At Hour 72	19125.715 ratio	Standard Deviation 14516.8397

Secondary

Parasite Clearance Rate

Parasite clearance rate (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite Clearance Estimator.

Time frame: Up to Day 28

Population: Analysis was performed on mITT population. Here, Overall Number of Participants Analyzed = participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Ferroquine 400 mg	Parasite Clearance Rate	0.1956 1 per hour	Standard Deviation 0.07627
Ferroquine 400 mg + Artefenomel 300 mg	Parasite Clearance Rate	0.3609 1 per hour	Standard Deviation 0.09963
Ferroquine 400 mg + Artefenomel 600 mg	Parasite Clearance Rate	0.3962 1 per hour	Standard Deviation 0.11983
Ferroquine 400 mg + Artefenomel 1000 mg	Parasite Clearance Rate	0.3581 1 per hour	Standard Deviation 0.12484

Secondary

Parasite Clearance Time (PCT)

PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites by microscopy). This first negative film was confirmed by a second negative film which was taken \>=6 to \<=12 hours of the first film. If the second film was performed \<6 hours or \>12 hours of the first film, then the parasite clearance was confirmed or invalidated by the third (thick) film following the second one, whatever the timing of this third film: If the third film was negative, then the clearance was considered confirmed and if the third film was positive, then the clearance was invalidated. Kaplan-Meier method was used for the estimation.

Time frame: From the start of study drug administration up to the time of the first negative blood film (up to Day 28)

Population: Analysis was performed on mITT population.

Arm	Measure	Value (MEDIAN)
Ferroquine 400 mg	Parasite Clearance Time (PCT)	56.1 hours
Ferroquine 400 mg + Artefenomel 300 mg	Parasite Clearance Time (PCT)	30.0 hours
Ferroquine 400 mg + Artefenomel 600 mg	Parasite Clearance Time (PCT)	30.0 hours
Ferroquine 400 mg + Artefenomel 1000 mg	Parasite Clearance Time (PCT)	30.0 hours

Secondary

Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours

Parasitemia (quantitative content of parasites present in the blood) at baseline until Day 7 (i.e. 168 hours) was assessed by optical microscope.

Time frame: Baseline, 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

Population: Analysis was performed on modified intention-to-treat (mITT) population which included all randomized participants with parasitological confirmed P.falciparum malaria at baseline with parasitemia data post-randomization, received the single administration of OZ439/FQ. Here, number analyzed = participants with available data for each specified category.

Arm	Measure	Group	Value (MEAN)	Dispersion
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 144 hours post-dose	-18526.0 parasites per microliter	Standard Deviation 11889.52
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 24 hours post-dose	-14238.4 parasites per microliter	Standard Deviation 11402.25
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 18 hours post-dose	-9181.2 parasites per microliter	Standard Deviation 11892.89
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 6 hours post-dose	-1349.3 parasites per microliter	Standard Deviation 11331.78
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 72 hours post-dose	-18231.8 parasites per microliter	Standard Deviation 11801.65
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 12 hours post-dose	-5721.5 parasites per microliter	Standard Deviation 12441.39
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 30 hours post-dose	-16571.1 parasites per microliter	Standard Deviation 12354.88
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 120 hours post-dose	-19280.0 parasites per microliter	Standard Deviation 12145.86
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 96 hours post-dose	-18287.6 parasites per microliter	Standard Deviation 12011.77
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 168 hours post-dose	-18962.8 parasites per microliter	Standard Deviation 11813.2
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 48 hours post-dose	-17595.3 parasites per microliter	Standard Deviation 12037.99
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 36 hours post-dose	-17036.9 parasites per microliter	Standard Deviation 12307.57
Ferroquine 400 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Baseline	17496.0 parasites per microliter	Standard Deviation 11889.55
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 72 hours post-dose	-18396.3 parasites per microliter	Standard Deviation 13091.47
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 36 hours post-dose	-18792.2 parasites per microliter	Standard Deviation 13548.16
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 12 hours post-dose	-11471.6 parasites per microliter	Standard Deviation 13399.27
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 144 hours post-dose	-19023.3 parasites per microliter	Standard Deviation 13198.28
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Baseline	18799.6 parasites per microliter	Standard Deviation 13559.14
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 6 hours post-dose	-96.9 parasites per microliter	Standard Deviation 11699.28
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 18 hours post-dose	-17021.4 parasites per microliter	Standard Deviation 13015.29
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 24 hours post-dose	-17939.0 parasites per microliter	Standard Deviation 13061.86
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 30 hours post-dose	-19110.5 parasites per microliter	Standard Deviation 13556.35
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 48 hours post-dose	-17706.1 parasites per microliter	Standard Deviation 13389.25
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 96 hours post-dose	-19024.7 parasites per microliter	Standard Deviation 13200.22
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 120 hours post-dose	-19024.7 parasites per microliter	Standard Deviation 13200.22
Ferroquine 400 mg + Artefenomel 300 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 168 hours post-dose	-18922.2 parasites per microliter	Standard Deviation 13141.19
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Baseline	15171.9 parasites per microliter	Standard Deviation 13012.53
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 24 hours post-dose	-10674.6 parasites per microliter	Standard Deviation 29868.45
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 36 hours post-dose	-14573.9 parasites per microliter	Standard Deviation 13623.86
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 30 hours post-dose	-13299.6 parasites per microliter	Standard Deviation 17452.15
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 144 hours post-dose	-15254.5 parasites per microliter	Standard Deviation 13190.39
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 12 hours post-dose	-4156.6 parasites per microliter	Standard Deviation 34663.71
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 48 hours post-dose	-14542.3 parasites per microliter	Standard Deviation 13547.11
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 72 hours post-dose	-15333.7 parasites per microliter	Standard Deviation 13382.41
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 96 hours post-dose	-15258.5 parasites per microliter	Standard Deviation 13191.95
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 168 hours post-dose	-15268.5 parasites per microliter	Standard Deviation 13388.49
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 6 hours post-dose	8515.4 parasites per microliter	Standard Deviation 44264.14
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 120 hours post-dose	-15265.3 parasites per microliter	Standard Deviation 13190.14
Ferroquine 400 mg + Artefenomel 600 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 18 hours post-dose	-9447.5 parasites per microliter	Standard Deviation 32303.36
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 18 hours post-dose	-18281.9 parasites per microliter	Standard Deviation 13796.37
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 120 hours post-dose	-20350.4 parasites per microliter	Standard Deviation 14010.21
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 72 hours post-dose	-20314.2 parasites per microliter	Standard Deviation 13980.12
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 24 hours post-dose	-19461.9 parasites per microliter	Standard Deviation 14049.02
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 96 hours post-dose	-20662.0 parasites per microliter	Standard Deviation 14108.54
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 168 hours post-dose	-20349.5 parasites per microliter	Standard Deviation 14010.98
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 30 hours post-dose	-19657.5 parasites per microliter	Standard Deviation 14393.75
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 144 hours post-dose	-20029.7 parasites per microliter	Standard Deviation 14121.74
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 36 hours post-dose	-19587.9 parasites per microliter	Standard Deviation 14051.82
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 12 hours post-dose	-11319.4 parasites per microliter	Standard Deviation 15490.43
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Baseline	20546.8 parasites per microliter	Standard Deviation 13835.31
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 6 hours post-dose	893.2 parasites per microliter	Standard Deviation 21052.27
Ferroquine 400 mg + Artefenomel 1000 mg	Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours	Change from baseline at 48 hours post-dose	-20327.7 parasites per microliter	Standard Deviation 13739.17

Secondary

Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28

ACPR: absence of parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS/SoC/SM at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia; or parasitemia on Day 2 \> Day 0 irrespective of AT; or parasitemia on Day 3 with AT \>=37.5°C; or parasitemia count on Day 3 \>=25% on Day 0, or LCF: DS/SM in presence of parasitemia between Day 4 and 28, concomitant to at least one positive parasitemia; or presence of parasitemia and AT\>=37.5°C on Day 4 to Day 28, or LPF: presence of parasitemia between Day 7 and 28 and AT\<37.5°C or having rescue therapy for malaria. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish reinfection (new clone of parasite) or recrudescence.

Time frame: Day 28

Population: Analysis was performed on PK/PD efficacy population.

Arm	Measure	Value (NUMBER)
Ferroquine 400 mg	Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28	64.5 percentage of participants
Ferroquine 400 mg + Artefenomel 300 mg	Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28	81.8 percentage of participants
Ferroquine 400 mg + Artefenomel 600 mg	Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28	77.8 percentage of participants
Ferroquine 400 mg + Artefenomel 1000 mg	Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28	78.1 percentage of participants

Secondary

Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel

Area under the plasma concentration versus time curve from time 0 to infinity. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.

Time frame: Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose

Population: Analysis was performed on PK/PD efficacy population.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ferroquine 400 mg	Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel	3.269 micrograms*hour per milliliter	Geometric Coefficient of Variation 113
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel	6.46 micrograms*hour per milliliter	Geometric Coefficient of Variation 181
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel	13.05 micrograms*hour per milliliter	Geometric Coefficient of Variation 114

Secondary

Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213

Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours).

Time frame: Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

Population: Analysis was performed on PK/PD efficacy population.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Ferroquine 400 mg	Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213	FQ	8.874 micrograms*hour per milliliter	Geometric Coefficient of Variation 42
Ferroquine 400 mg	Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213	SSR97213	8.878 micrograms*hour per milliliter	Geometric Coefficient of Variation 48
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213	SSR97213	9.051 micrograms*hour per milliliter	Geometric Coefficient of Variation 56
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213	FQ	10.33 micrograms*hour per milliliter	Geometric Coefficient of Variation 40
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213	FQ	10.13 micrograms*hour per milliliter	Geometric Coefficient of Variation 51
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213	SSR97213	8.483 micrograms*hour per milliliter	Geometric Coefficient of Variation 68
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213	FQ	10.14 micrograms*hour per milliliter	Geometric Coefficient of Variation 56
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213	SSR97213	8.487 micrograms*hour per milliliter	Geometric Coefficient of Variation 71

Secondary

Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213

Area under the plasma concentration versus time curve from time 0 to infinity.

Time frame: Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

Population: Analysis was performed on PK/PD efficacy population.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Ferroquine 400 mg	Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213	FQ	15.5 micrograms*hour per milliliter	Geometric Coefficient of Variation 47
Ferroquine 400 mg	Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213	SSR97213	19.58 micrograms*hour per milliliter	Geometric Coefficient of Variation 53
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213	FQ	17.81 micrograms*hour per milliliter	Geometric Coefficient of Variation 43
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213	SSR97213	20.09 micrograms*hour per milliliter	Geometric Coefficient of Variation 48
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213	SSR97213	17.94 micrograms*hour per milliliter	Geometric Coefficient of Variation 69
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213	FQ	16.3 micrograms*hour per milliliter	Geometric Coefficient of Variation 63
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213	FQ	16.87 micrograms*hour per milliliter	Geometric Coefficient of Variation 59
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213	SSR97213	18.32 micrograms*hour per milliliter	Geometric Coefficient of Variation 68

Secondary

Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood

Concentrations of FQ and SSR97213 in blood was analyzed by LC-MS/MS. The LLOQ was 5 nanograms per milliliter for analysis of FQ and SSR97213.

Time frame: 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

Population: Analysis was performed on PK population which included all participants who received FQ and had at least one evaluable blood sample for PK FQ post study drug administration and with adequate documentation of date of dosing and date of sampling. Here, 'number analyzed' = participants with available data for each specified category.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	1 hour post-dose: FQ	36.094 nanograms per milliliter	Geometric Coefficient of Variation 80.476
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	1 hour post-dose: SSR97213	13.209 nanograms per milliliter	Geometric Coefficient of Variation 54.03
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	4 hours post-dose: SSR97213	20.079 nanograms per milliliter	Geometric Coefficient of Variation 90.358
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	6 hours post-dose: SSR97213	23.170 nanograms per milliliter	Geometric Coefficient of Variation 82.875
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	6 hours post-dose: FQ	69.005 nanograms per milliliter	Geometric Coefficient of Variation 75.045
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	8 hours post-dose: FQ	64.293 nanograms per milliliter	Geometric Coefficient of Variation 70.724
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	8 hours post-dose: SSR97213	25.131 nanograms per milliliter	Geometric Coefficient of Variation 66.944
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	12 hours post-dose: FQ	50.621 nanograms per milliliter	Geometric Coefficient of Variation 57.54
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	12 hours post-dose: SSR97213	19.957 nanograms per milliliter	Geometric Coefficient of Variation 61.856
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	24 hours post-dose: FQ	44.351 nanograms per milliliter	Geometric Coefficient of Variation 52.316
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	24 hours post-dose: SSR97213	18.874 nanograms per milliliter	Geometric Coefficient of Variation 56.412
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	72 hours post-dose: FQ	25.343 nanograms per milliliter	Geometric Coefficient of Variation 35.315
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	72 hours post-dose: SSR97213	16.757 nanograms per milliliter	Geometric Coefficient of Variation 46.038
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	168 hours post-dose: FQ	16.973 nanograms per milliliter	Geometric Coefficient of Variation 39.627
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	168 hours post-dose: SSR97213	16.308 nanograms per milliliter	Geometric Coefficient of Variation 52.3
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	336 hours post-dose: FQ	10.543 nanograms per milliliter	Geometric Coefficient of Variation 36.77
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	336 hours post-dose: SSR97213	13.612 nanograms per milliliter	Geometric Coefficient of Variation 45.485
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	672 hours post-dose: FQ	6.737 nanograms per milliliter	Geometric Coefficient of Variation 18.832
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	672 hours post-dose: SSR97213	9.751 nanograms per milliliter	Geometric Coefficient of Variation 41.862
Ferroquine 400 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	4 hours post-dose: FQ	64.934 nanograms per milliliter	Geometric Coefficient of Variation 87.235
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	1 hour post-dose: FQ	27.214 nanograms per milliliter	Geometric Coefficient of Variation 79
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	672 hours post-dose: SSR97213	10.324 nanograms per milliliter	Geometric Coefficient of Variation 33.482
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	12 hours post-dose: FQ	68.384 nanograms per milliliter	Geometric Coefficient of Variation 50.887
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	12 hours post-dose: SSR97213	24.385 nanograms per milliliter	Geometric Coefficient of Variation 48.408
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	24 hours post-dose: FQ	53.211 nanograms per milliliter	Geometric Coefficient of Variation 48.834
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	24 hours post-dose: SSR97213	22.967 nanograms per milliliter	Geometric Coefficient of Variation 55.037
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	72 hours post-dose: FQ	31.161 nanograms per milliliter	Geometric Coefficient of Variation 47.829
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	1 hour post-dose: SSR97213	10.375 nanograms per milliliter	Geometric Coefficient of Variation 15.713
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	72 hours post-dose: SSR97213	20.059 nanograms per milliliter	Geometric Coefficient of Variation 45.134
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	168 hours post-dose: FQ	20.524 nanograms per milliliter	Geometric Coefficient of Variation 39.625
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	168 hours post-dose: SSR97213	19.196 nanograms per milliliter	Geometric Coefficient of Variation 46.115
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	336 hours post-dose: FQ	11.678 nanograms per milliliter	Geometric Coefficient of Variation 38.49
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	4 hours post-dose: FQ	100.569 nanograms per milliliter	Geometric Coefficient of Variation 61.578
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	336 hours post-dose: SSR97213	14.797 nanograms per milliliter	Geometric Coefficient of Variation 46.036
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	4 hours post-dose: SSR97213	29.632 nanograms per milliliter	Geometric Coefficient of Variation 49.701
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	6 hours post-dose: FQ	92.657 nanograms per milliliter	Geometric Coefficient of Variation 50.449
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	672 hours post-dose: FQ	7.623 nanograms per milliliter	Geometric Coefficient of Variation 28.348
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	6 hours post-dose: SSR97213	28.098 nanograms per milliliter	Geometric Coefficient of Variation 53.438
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	8 hours post-dose: FQ	82.639 nanograms per milliliter	Geometric Coefficient of Variation 49.891
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	8 hours post-dose: SSR97213	29.319 nanograms per milliliter	Geometric Coefficient of Variation 48.679
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	6 hours post-dose: FQ	84.803 nanograms per milliliter	Geometric Coefficient of Variation 75.544
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	8 hours post-dose: FQ	78.196 nanograms per milliliter	Geometric Coefficient of Variation 72.454
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	72 hours post-dose: SSR97213	21.315 nanograms per milliliter	Geometric Coefficient of Variation 68.366
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	1 hour post-dose: SSR97213	6.161 nanograms per milliliter	Geometric Coefficient of Variation 9.504
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	168 hours post-dose: FQ	21.543 nanograms per milliliter	Geometric Coefficient of Variation 63.679
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	672 hours post-dose: FQ	7.601 nanograms per milliliter	Geometric Coefficient of Variation 29.047
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	168 hours post-dose: SSR97213	20.463 nanograms per milliliter	Geometric Coefficient of Variation 55.587
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	4 hours post-dose: SSR97213	18.377 nanograms per milliliter	Geometric Coefficient of Variation 98.31
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	336 hours post-dose: FQ	12.469 nanograms per milliliter	Geometric Coefficient of Variation 48.236
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	6 hours post-dose: SSR97213	25.954 nanograms per milliliter	Geometric Coefficient of Variation 88.481
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	336 hours post-dose: SSR97213	15.647 nanograms per milliliter	Geometric Coefficient of Variation 47.974
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	12 hours post-dose: FQ	59.106 nanograms per milliliter	Geometric Coefficient of Variation 70.461
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	672 hours post-dose: SSR97213	10.977 nanograms per milliliter	Geometric Coefficient of Variation 34.251
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	4 hours post-dose: FQ	79.656 nanograms per milliliter	Geometric Coefficient of Variation 74.707
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	12 hours post-dose: SSR97213	20.615 nanograms per milliliter	Geometric Coefficient of Variation 77.739
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	24 hours post-dose: FQ	47.568 nanograms per milliliter	Geometric Coefficient of Variation 61.373
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	8 hours post-dose: SSR97213	25.304 nanograms per milliliter	Geometric Coefficient of Variation 78.822
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	24 hours post-dose: SSR97213	19.826 nanograms per milliliter	Geometric Coefficient of Variation 70.907
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	1 hour post-dose: FQ	21.165 nanograms per milliliter	Geometric Coefficient of Variation 55.491
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	72 hours post-dose: FQ	31.373 nanograms per milliliter	Geometric Coefficient of Variation 70.287
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	672 hours post-dose: SSR97213	12.014 nanograms per milliliter	Geometric Coefficient of Variation 59.403
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	72 hours post-dose: FQ	29.792 nanograms per milliliter	Geometric Coefficient of Variation 76.912
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	6 hours post-dose: FQ	95.062 nanograms per milliliter	Geometric Coefficient of Variation 126.388
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	8 hours post-dose: SSR97213	20.299 nanograms per milliliter	Geometric Coefficient of Variation 63.388
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	1 hour post-dose: FQ	26.599 nanograms per milliliter	Geometric Coefficient of Variation 95.999
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	72 hours post-dose: SSR97213	17.756 nanograms per milliliter	Geometric Coefficient of Variation 82.612
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	336 hours post-dose: SSR97213	13.686 nanograms per milliliter	Geometric Coefficient of Variation 72.213
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	4 hours post-dose: SSR97213	17.559 nanograms per milliliter	Geometric Coefficient of Variation 68.694
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	672 hours post-dose: FQ	7.342 nanograms per milliliter	Geometric Coefficient of Variation 53.998
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	168 hours post-dose: FQ	21.322 nanograms per milliliter	Geometric Coefficient of Variation 62.951
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	1 hour post-dose: SSR97213	6.805 nanograms per milliliter	Geometric Coefficient of Variation 28.203
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	12 hours post-dose: FQ	71.743 nanograms per milliliter	Geometric Coefficient of Variation 61.238
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	4 hours post-dose: FQ	97.007 nanograms per milliliter	Geometric Coefficient of Variation 72.23
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	168 hours post-dose: SSR97213	19.108 nanograms per milliliter	Geometric Coefficient of Variation 62.123
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	24 hours post-dose: FQ	51.250 nanograms per milliliter	Geometric Coefficient of Variation 75.94
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	8 hours post-dose: FQ	82.990 nanograms per milliliter	Geometric Coefficient of Variation 69.989
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	24 hours post-dose: SSR97213	16.763 nanograms per milliliter	Geometric Coefficient of Variation 69.091
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	336 hours post-dose: FQ	11.263 nanograms per milliliter	Geometric Coefficient of Variation 82.611
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	12 hours post-dose: SSR97213	18.203 nanograms per milliliter	Geometric Coefficient of Variation 64.197
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood	6 hours post-dose: SSR97213	20.687 nanograms per milliliter	Geometric Coefficient of Variation 70.211

Secondary

Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel

Cmax is the maximum observed plasma concentration of Artefenomel. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.

Time frame: Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose

Population: Analysis was performed on PK/PD efficacy population.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ferroquine 400 mg	Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel	277.3 nanograms per milliliter	Geometric Coefficient of Variation 169
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel	488.3 nanograms per milliliter	Geometric Coefficient of Variation 232
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel	920.6 nanograms per milliliter	Geometric Coefficient of Variation 77

Secondary

Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213

Cmax is the maximum observed plasma concentration of Ferroquine.

Time frame: Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

Population: Analysis was performed on PK/PD efficacy population.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Ferroquine 400 mg	Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	FQ	80.99 nanograms per milliliter	Geometric Coefficient of Variation 61
Ferroquine 400 mg	Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	SSR97213	24.58 nanograms per milliliter	Geometric Coefficient of Variation 61
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	SSR97213	22.65 nanograms per milliliter	Geometric Coefficient of Variation 83
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	FQ	79.95 nanograms per milliliter	Geometric Coefficient of Variation 93
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	FQ	72.64 nanograms per milliliter	Geometric Coefficient of Variation 88
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	SSR97213	19.14 nanograms per milliliter	Geometric Coefficient of Variation 99
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	FQ	82.45 nanograms per milliliter	Geometric Coefficient of Variation 95
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213	SSR97213	19.76 nanograms per milliliter	Geometric Coefficient of Variation 78

Secondary

Pharmacokinetics (PK): Concentration of OZ439 in Plasma

Concentrations of OZ439 in plasma was analyzed by liquid chromatography tandem mass spectroscopy (LC-MS/MS). The lower limit of quantification (LLOQ) was 1 nanograms per milliliter for analysis of OZ439. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.

Time frame: 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose

Population: Analysis was performed on PK population which included all participants who received OZ439 and had at least one evaluable blood sample for PK OZ439 post study drug administration and with adequate documentation of date of dosing and date of sampling. Here, 'number analyzed' = participants with available data for each specified category.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	336 hours post-dose	1.227 nanograms per milliliter	Geometric Coefficient of Variation 19.402
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	12 hours post-dose	92.614 nanograms per milliliter	Geometric Coefficient of Variation 60.229
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	168 hours post-dose	1.745 nanograms per milliliter	Geometric Coefficient of Variation 38.466
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	1 hour post-dose	88.641 nanograms per milliliter	Geometric Coefficient of Variation 104.631
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	2 hours post-dose	269.075 nanograms per milliliter	Geometric Coefficient of Variation 59.803
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	4 hours post-dose	349.134 nanograms per milliliter	Geometric Coefficient of Variation 54.88
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	6 hours post-dose	234.375 nanograms per milliliter	Geometric Coefficient of Variation 52.902
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	24 hours post-dose	17.526 nanograms per milliliter	Geometric Coefficient of Variation 65.757
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	48 hours post-dose	6.097 nanograms per milliliter	Geometric Coefficient of Variation 54.492
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	72 hours post-dose	3.224 nanograms per milliliter	Geometric Coefficient of Variation 50.406
Ferroquine 400 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	120 hours post-dose	2.144 nanograms per milliliter	Geometric Coefficient of Variation 39.859
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	2 hours post-dose	450.218 nanograms per milliliter	Geometric Coefficient of Variation 58.642
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	4 hours post-dose	576.673 nanograms per milliliter	Geometric Coefficient of Variation 54.357
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	120 hours post-dose	5.339 nanograms per milliliter	Geometric Coefficient of Variation 61.816
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	6 hours post-dose	478.929 nanograms per milliliter	Geometric Coefficient of Variation 87.523
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	24 hours post-dose	48.257 nanograms per milliliter	Geometric Coefficient of Variation 107.605
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	168 hours post-dose	3.408 nanograms per milliliter	Geometric Coefficient of Variation 73.232
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	48 hours post-dose	14.611 nanograms per milliliter	Geometric Coefficient of Variation 95.627
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	12 hours post-dose	164.028 nanograms per milliliter	Geometric Coefficient of Variation 99.433
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	336 hours post-dose	1.970 nanograms per milliliter	Geometric Coefficient of Variation 66.212
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	72 hours post-dose	8.162 nanograms per milliliter	Geometric Coefficient of Variation 77.493
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	1 hour post-dose	149.199 nanograms per milliliter	Geometric Coefficient of Variation 87.153
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	72 hours post-dose	16.665 nanograms per milliliter	Geometric Coefficient of Variation 83.936
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	2 hours post-dose	655.851 nanograms per milliliter	Geometric Coefficient of Variation 58.311
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	1 hour post-dose	188.423 nanograms per milliliter	Geometric Coefficient of Variation 82.588
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	6 hours post-dose	865.581 nanograms per milliliter	Geometric Coefficient of Variation 75.154
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	4 hours post-dose	978.649 nanograms per milliliter	Geometric Coefficient of Variation 60.263
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	48 hours post-dose	29.554 nanograms per milliliter	Geometric Coefficient of Variation 83.028
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	336 hours post-dose	3.149 nanograms per milliliter	Geometric Coefficient of Variation 58.029
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	120 hours post-dose	8.596 nanograms per milliliter	Geometric Coefficient of Variation 77.245
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	12 hours post-dose	369.335 nanograms per milliliter	Geometric Coefficient of Variation 85.243
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	24 hours post-dose	84.167 nanograms per milliliter	Geometric Coefficient of Variation 78.221
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics (PK): Concentration of OZ439 in Plasma	168 hours post-dose	5.903 nanograms per milliliter	Geometric Coefficient of Variation 78.608

Secondary

Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel

The observed plasma concentration of artefenomel post 168 hours of drug administration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.

Time frame: At 168 hours post-dose

Population: Analysis was performed on PK/PD efficacy population.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ferroquine 400 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel	0.9251 nanograms per milliliter	Geometric Coefficient of Variation 110
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel	2.152 nanograms per milliliter	Geometric Coefficient of Variation 202
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel	4.445 nanograms per milliliter	Geometric Coefficient of Variation 165

Secondary

Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213

The observed plasma concentration of FQ and SSR97213 post 168 hours of FQ administration.

Time frame: At 168 hours post-dose

Population: Analysis was performed on PK/PD efficacy population.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Ferroquine 400 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213	SSR97213	16.15 nanograms per milliliter	Geometric Coefficient of Variation 51
Ferroquine 400 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213	FQ	15.86 nanograms per milliliter	Geometric Coefficient of Variation 44
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213	SSR97213	16.03 nanograms per milliliter	Geometric Coefficient of Variation 68
Ferroquine 400 mg + Artefenomel 300 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213	FQ	18.32 nanograms per milliliter	Geometric Coefficient of Variation 42
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213	FQ	18.69 nanograms per milliliter	Geometric Coefficient of Variation 52
Ferroquine 400 mg + Artefenomel 600 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213	SSR97213	15.2 nanograms per milliliter	Geometric Coefficient of Variation 78
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213	SSR97213	14.95 nanograms per milliliter	Geometric Coefficient of Variation 86
Ferroquine 400 mg + Artefenomel 1000 mg	Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213	FQ	17.83 nanograms per milliliter	Geometric Coefficient of Variation 60

Secondary

Pharmacokinetics: Terminal Half-life of Ferroquine

Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration.

Time frame: Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

Population: Focus of PK assessment was to support the analysis of exposure versus efficacy relationship (PK and PD). Since terminal t1/2 was not considered relevant to the objective of exposure-response analysis, therefore data for this outcome measure were not collected and reported.

Secondary

Pharmacokinetics: Terminal Half-life (t1/2) of Artefenomel

Terminal t1/2 is defined as the time required for the plasma concentration of a drug to decrease by half of its initial concentration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.

Time frame: Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose

Secondary

Pharmacokinetics: Time to Reach Maximum Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213

tmax is the time taken by the drug to reach the maximum plasma concentration.

Time frame: Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

Population: Focus of PK assessment was to support the analysis of exposure versus efficacy relationship (PK and PD). Since tmax was not considered relevant to the objective of exposure-response analysis, therefore data for this outcome measure were not collected and reported.

Secondary

Pharmacokinetics: Time to Reach Maximum Plasma Concentration (Tmax) of Artefenomel

tmax is the time taken by the drug to reach the maximum plasma concentration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered.

Time frame: Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose

Population: Focus of PK assessment was to support the analysis of exposure versus efficacy relationship (PK and PD). Since tmax was not considered relevant to the objective of exposure-response analysis, data for this outcome measure were not collected and reported.

Secondary

Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia

The time elapsed below LOQ (LOQ expressed in parasites/microliter) of parasitemia (quantitative content of parasites present in the blood) was defined as the time (in days) for which no parasites were seen i.e., time corresponding to PCT, up to the time of occurrence of a new malaria infection or recrudescence. If there was no occurrence of a new malaria infection or recrudescence, then this was the time corresponding to the first negative thick blood film, until the end of study. PCT (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite clearance estimator. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Meier method was used for estimation.

Time frame: Up to Day 28

Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
Ferroquine 400 mg	Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia	25.0 days
Ferroquine 400 mg + Artefenomel 300 mg	Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia	26.0 days
Ferroquine 400 mg + Artefenomel 600 mg	Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia	26.5 days
Ferroquine 400 mg + Artefenomel 1000 mg	Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia	26.0 days

Secondary

Time to 50% and 99% Parasite Reduction

Time to 50% and 99% parasite reduction was defined as time needed for the parasitemia (quantitative content of parasites present in blood) to be reduced to 50% and 99% of the initial value, respectively.

Time frame: Up to Day 28

Population: Analysis was performed on mITT population. Here, Overall Number of Participants Analyzed = participants evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
Ferroquine 400 mg	Time to 50% and 99% Parasite Reduction	Time to 50% Parasite reduction	14.07 hours	Standard Deviation 5.604
Ferroquine 400 mg	Time to 50% and 99% Parasite Reduction	Time to 99% Parasite reduction	36.92 hours	Standard Deviation 9.988
Ferroquine 400 mg + Artefenomel 300 mg	Time to 50% and 99% Parasite Reduction	Time to 99% Parasite reduction	19.33 hours	Standard Deviation 6.107
Ferroquine 400 mg + Artefenomel 300 mg	Time to 50% and 99% Parasite Reduction	Time to 50% Parasite reduction	7.74 hours	Standard Deviation 4.636
Ferroquine 400 mg + Artefenomel 600 mg	Time to 50% and 99% Parasite Reduction	Time to 99% Parasite reduction	18.34 hours	Standard Deviation 5.523
Ferroquine 400 mg + Artefenomel 600 mg	Time to 50% and 99% Parasite Reduction	Time to 50% Parasite reduction	7.78 hours	Standard Deviation 3.786
Ferroquine 400 mg + Artefenomel 1000 mg	Time to 50% and 99% Parasite Reduction	Time to 50% Parasite reduction	9.47 hours	Standard Deviation 7.976
Ferroquine 400 mg + Artefenomel 1000 mg	Time to 50% and 99% Parasite Reduction	Time to 99% Parasite reduction	22.95 hours	Standard Deviation 17.069

Secondary

Time to Recrudescence

Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation.

Time frame: Up to Day 28

Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
Ferroquine 400 mg	Time to Recrudescence	NA days
Ferroquine 400 mg + Artefenomel 300 mg	Time to Recrudescence	NA days
Ferroquine 400 mg + Artefenomel 600 mg	Time to Recrudescence	NA days
Ferroquine 400 mg + Artefenomel 1000 mg	Time to Recrudescence	NA days

Secondary

Time to Re-emergence

Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Re-emergence was confirmed by microscopy (positive blood smear). Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation.

Time frame: Up to Day 28

Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
Ferroquine 400 mg	Time to Re-emergence	NA days
Ferroquine 400 mg + Artefenomel 300 mg	Time to Re-emergence	NA days
Ferroquine 400 mg + Artefenomel 600 mg	Time to Re-emergence	NA days
Ferroquine 400 mg + Artefenomel 1000 mg	Time to Re-emergence	NA days

Secondary

Time to Re-infection

Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differed from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Maier method was used for estimation.

Time frame: Up to Day 28

Population: Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
Ferroquine 400 mg	Time to Re-infection	NA days
Ferroquine 400 mg + Artefenomel 300 mg	Time to Re-infection	NA days
Ferroquine 400 mg + Artefenomel 600 mg	Time to Re-infection	NA days
Ferroquine 400 mg + Artefenomel 1000 mg	Time to Re-infection	NA days

Source: ClinicalTrials.gov · Data processed: Feb 13, 2026

Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)

Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours

Parasite Clearance Rate

Parasite Clearance Time (PCT)

Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours

Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28

Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel

Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213

Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213

Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood

Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel

Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213

Pharmacokinetics (PK): Concentration of OZ439 in Plasma

Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel

Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213

Pharmacokinetics: Terminal Half-life of Ferroquine

Pharmacokinetics: Terminal Half-life (t1/2) of Artefenomel

Pharmacokinetics: Time to Reach Maximum Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213

Pharmacokinetics: Time to Reach Maximum Plasma Concentration (Tmax) of Artefenomel

Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia

Time to 50% and 99% Parasite Reduction

Time to Recrudescence

Time to Re-emergence

Time to Re-infection