Trial Outcomes & Findings for Study to Investigate the Clinical and Parasiticidal Activity and Pharmacokinetics of Different Doses of Artefenomel and Ferroquine in Patients With Uncomplicated Plasmodium Falciparum Malaria (NCT NCT03660839)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

140 participants

Primary outcome timeframe

Day 28

Results posted on

2022-03-21

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Ferroquine (FQ) 400 Milligram (mg) On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel (OZ439) 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.	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.	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.
Overall Study STARTED	35	36	36	33
Overall Study COMPLETED	35	36	36	33
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ferroquine 400 mg n=35 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=33 Participants 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.	Total n=140 Participants Total of all reporting groups
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Continuous	25.4 years STANDARD_DEVIATION 13.20 • n=5 Participants	21.8 years STANDARD_DEVIATION 11.49 • n=7 Participants	20.7 years STANDARD_DEVIATION 8.57 • n=5 Participants	22.2 years STANDARD_DEVIATION 11.28 • n=4 Participants	22.5 years STANDARD_DEVIATION 11.26 • n=21 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	28 Participants n=7 Participants	26 Participants n=5 Participants	20 Participants n=4 Participants	97 Participants n=21 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants	13 Participants n=4 Participants	43 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	35 Participants n=5 Participants	36 Participants n=7 Participants	35 Participants n=5 Participants	33 Participants n=4 Participants	139 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=26 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=31 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=33 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=31 Participants 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.
Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)	80.8 percentage of participants Interval 62.1 to 91.5	90.3 percentage of participants Interval 75.1 to 96.7	90.9 percentage of participants Interval 76.4 to 96.9	87.1 percentage of participants Interval 71.1 to 94.9

SECONDARY outcome

Timeframe: Day 28

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

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=31 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=33 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=32 Participants 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.
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28	64.5 percentage of participants Interval 46.9 to 78.9	81.8 percentage of participants Interval 65.6 to 91.4	77.8 percentage of participants Interval 61.9 to 88.3	78.1 percentage of participants Interval 61.2 to 89.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=35 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=33 Participants 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.
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	18799.6 parasites per microliter Standard Deviation 13559.14	15171.9 parasites per microliter Standard Deviation 13012.53	20546.8 parasites per microliter Standard Deviation 13835.31
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	-96.9 parasites per microliter Standard Deviation 11699.28	8515.4 parasites per microliter Standard Deviation 44264.14	893.2 parasites per microliter Standard Deviation 21052.27
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	-11471.6 parasites per microliter Standard Deviation 13399.27	-4156.6 parasites per microliter Standard Deviation 34663.71	-11319.4 parasites per microliter Standard Deviation 15490.43
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	-17021.4 parasites per microliter Standard Deviation 13015.29	-9447.5 parasites per microliter Standard Deviation 32303.36	-18281.9 parasites per microliter Standard Deviation 13796.37
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	-17939.0 parasites per microliter Standard Deviation 13061.86	-10674.6 parasites per microliter Standard Deviation 29868.45	-19461.9 parasites per microliter Standard Deviation 14049.02
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	-19110.5 parasites per microliter Standard Deviation 13556.35	-13299.6 parasites per microliter Standard Deviation 17452.15	-19657.5 parasites per microliter Standard Deviation 14393.75
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	-18792.2 parasites per microliter Standard Deviation 13548.16	-14573.9 parasites per microliter Standard Deviation 13623.86	-19587.9 parasites per microliter Standard Deviation 14051.82
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	-17706.1 parasites per microliter Standard Deviation 13389.25	-14542.3 parasites per microliter Standard Deviation 13547.11	-20327.7 parasites per microliter Standard Deviation 13739.17
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	-18396.3 parasites per microliter Standard Deviation 13091.47	-15333.7 parasites per microliter Standard Deviation 13382.41	-20314.2 parasites per microliter Standard Deviation 13980.12
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	-19024.7 parasites per microliter Standard Deviation 13200.22	-15258.5 parasites per microliter Standard Deviation 13191.95	-20662.0 parasites per microliter Standard Deviation 14108.54
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	-19024.7 parasites per microliter Standard Deviation 13200.22	-15265.3 parasites per microliter Standard Deviation 13190.14	-20350.4 parasites per microliter Standard Deviation 14010.21
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	-19023.3 parasites per microliter Standard Deviation 13198.28	-15254.5 parasites per microliter Standard Deviation 13190.39	-20029.7 parasites per microliter Standard Deviation 14121.74
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 11813.20	-18922.2 parasites per microliter Standard Deviation 13141.19	-15268.5 parasites per microliter Standard Deviation 13388.49	-20349.5 parasites per microliter Standard Deviation 14010.98

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=35 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=33 Participants 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.
Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours At Hour 24	638.436 ratio Standard Deviation 2013.8609	5921.197 ratio Standard Deviation 11566.1520	5715.046 ratio Standard Deviation 9364.8892	7929.720 ratio Standard Deviation 12675.8348
Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours At Hour 48	9709.093 ratio Standard Deviation 13987.7127	17594.700 ratio Standard Deviation 13521.9507	13120.409 ratio Standard Deviation 13182.3022	19328.057 ratio Standard Deviation 14392.7604
Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours At Hour 72	15655.447 ratio Standard Deviation 12806.4644	18069.583 ratio Standard Deviation 13409.1341	14561.409 ratio Standard Deviation 13657.0665	19125.715 ratio Standard Deviation 14516.8397

SECONDARY outcome

Timeframe: Up to Day 28

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

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=21 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=28 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=28 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=25 Participants 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.
Time to 50% and 99% Parasite Reduction Time to 50% Parasite reduction	14.07 hours Standard Deviation 5.604	7.74 hours Standard Deviation 4.636	7.78 hours Standard Deviation 3.786	9.47 hours Standard Deviation 7.976
Time to 50% and 99% Parasite Reduction Time to 99% Parasite reduction	36.92 hours Standard Deviation 9.988	19.33 hours Standard Deviation 6.107	18.34 hours Standard Deviation 5.523	22.95 hours Standard Deviation 17.069

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=35 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=33 Participants 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.
Parasite Clearance Time (PCT)	56.1 hours Interval 48.0 to 72.0	30.0 hours Interval 30.0 to 30.0	30.0 hours Interval 24.1 to 30.1	30.0 hours Interval 24.0 to 30.0

SECONDARY outcome

Timeframe: Up to Day 28

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

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=21 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=28 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=28 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=25 Participants 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.
Parasite Clearance Rate	0.1956 1 per hour Standard Deviation 0.07627	0.3609 1 per hour Standard Deviation 0.09963	0.3962 1 per hour Standard Deviation 0.11983	0.3581 1 per hour Standard Deviation 0.12484

SECONDARY outcome

Timeframe: Up to Day 28

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

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=32 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=35 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=34 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=32 Participants 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.
Time to Re-emergence	NA days Interval 28.0 to Median and upper limit of confidence interval (CI) was not estimable due to very low number of participants with events.	NA days Median and 95% CI was not estimable due to very low number of participants with the events .	NA days Median and 95% CI was not estimable due to very low number of participants with the events .	NA days Median and 95% CI was not estimable due to very low number of participants with the events .

SECONDARY outcome

Timeframe: Up to Day 28

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

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=32 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=35 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=34 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=32 Participants 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.
Time to Recrudescence	NA days Median and 95% CI was not estimable due to very low number of participants with the events.	NA days Median and 95% CI was not estimable due to very low number of participants with the events.	NA days Median and 95% CI was not estimable due to very low number of participants with the events.	NA days Median and 95% CI was not estimable due to very low number of participants with the events.

SECONDARY outcome

Timeframe: Up to Day 28

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

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=32 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=35 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=34 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=32 Participants 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.
Time to Re-infection	NA days Median and 95% CI was not estimable due to very low number of participants with the events.	NA days Median and 95% CI was not estimable due to very low number of participants with the events.	NA days Median and 95% CI was not estimable due to very low number of participants with the events.	NA days Median and 95% CI was not estimable due to very low number of participants with the events.

SECONDARY outcome

Timeframe: Up to Day 28

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

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=32 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=35 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=34 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=32 Participants 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.
Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia	25.0 days Interval 23.0 to 26.0	26.0 days Interval 26.0 to 27.0	26.5 days Interval 26.0 to 27.0	26.0 days Interval 26.0 to 27.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=35 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=33 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI) Any TEAE	18 Participants	21 Participants	24 Participants	24 Participants
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	0 Participants	1 Participants	0 Participants
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	1 Participants	0 Participants	1 Participants
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	0 Participants	0 Participants	0 Participants
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	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=36 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=33 Participants 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.	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.
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 1 hour post-dose	88.641 nanograms per milliliter Geometric Coefficient of Variation 104.631	149.199 nanograms per milliliter Geometric Coefficient of Variation 87.153	188.423 nanograms per milliliter Geometric Coefficient of Variation 82.588	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 2 hours post-dose	269.075 nanograms per milliliter Geometric Coefficient of Variation 59.803	450.218 nanograms per milliliter Geometric Coefficient of Variation 58.642	655.851 nanograms per milliliter Geometric Coefficient of Variation 58.311	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 4 hours post-dose	349.134 nanograms per milliliter Geometric Coefficient of Variation 54.880	576.673 nanograms per milliliter Geometric Coefficient of Variation 54.357	978.649 nanograms per milliliter Geometric Coefficient of Variation 60.263	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 6 hours post-dose	234.375 nanograms per milliliter Geometric Coefficient of Variation 52.902	478.929 nanograms per milliliter Geometric Coefficient of Variation 87.523	865.581 nanograms per milliliter Geometric Coefficient of Variation 75.154	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 12 hours post-dose	92.614 nanograms per milliliter Geometric Coefficient of Variation 60.229	164.028 nanograms per milliliter Geometric Coefficient of Variation 99.433	369.335 nanograms per milliliter Geometric Coefficient of Variation 85.243	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 24 hours post-dose	17.526 nanograms per milliliter Geometric Coefficient of Variation 65.757	48.257 nanograms per milliliter Geometric Coefficient of Variation 107.605	84.167 nanograms per milliliter Geometric Coefficient of Variation 78.221	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 48 hours post-dose	6.097 nanograms per milliliter Geometric Coefficient of Variation 54.492	14.611 nanograms per milliliter Geometric Coefficient of Variation 95.627	29.554 nanograms per milliliter Geometric Coefficient of Variation 83.028	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 72 hours post-dose	3.224 nanograms per milliliter Geometric Coefficient of Variation 50.406	8.162 nanograms per milliliter Geometric Coefficient of Variation 77.493	16.665 nanograms per milliliter Geometric Coefficient of Variation 83.936	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 120 hours post-dose	2.144 nanograms per milliliter Geometric Coefficient of Variation 39.859	5.339 nanograms per milliliter Geometric Coefficient of Variation 61.816	8.596 nanograms per milliliter Geometric Coefficient of Variation 77.245	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 168 hours post-dose	1.745 nanograms per milliliter Geometric Coefficient of Variation 38.466	3.408 nanograms per milliliter Geometric Coefficient of Variation 73.232	5.903 nanograms per milliliter Geometric Coefficient of Variation 78.608	—
Pharmacokinetics (PK): Concentration of OZ439 in Plasma 336 hours post-dose	1.227 nanograms per milliliter Geometric Coefficient of Variation 19.402	1.970 nanograms per milliliter Geometric Coefficient of Variation 66.212	3.149 nanograms per milliliter Geometric Coefficient of Variation 58.029	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=33 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=32 Participants 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.	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.
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel	277.3 nanograms per milliliter Geometric Coefficient of Variation 169	488.3 nanograms per milliliter Geometric Coefficient of Variation 232	920.6 nanograms per milliliter Geometric Coefficient of Variation 77	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 168 hours post-dose

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

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=33 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=32 Participants 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.	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.
Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel	0.9251 nanograms per milliliter Geometric Coefficient of Variation 110	2.152 nanograms per milliliter Geometric Coefficient of Variation 202	4.445 nanograms per milliliter Geometric Coefficient of Variation 165	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=33 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=32 Participants 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.	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.
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	6.46 micrograms*hour per milliliter Geometric Coefficient of Variation 181	13.05 micrograms*hour per milliliter Geometric Coefficient of Variation 114	—

SECONDARY outcome

Timeframe: 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 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Cmax is the maximum observed plasma concentration of Ferroquine.

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=31 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=33 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=32 Participants 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.
Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213 FQ	80.99 nanograms per milliliter Geometric Coefficient of Variation 61	79.95 nanograms per milliliter Geometric Coefficient of Variation 93	72.64 nanograms per milliliter Geometric Coefficient of Variation 88	82.45 nanograms per milliliter Geometric Coefficient of Variation 95
Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213 SSR97213	24.58 nanograms per milliliter Geometric Coefficient of Variation 61	22.65 nanograms per milliliter Geometric Coefficient of Variation 83	19.14 nanograms per milliliter Geometric Coefficient of Variation 99	19.76 nanograms per milliliter Geometric Coefficient of Variation 78

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 168 hours post-dose

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

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

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=31 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=33 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=32 Participants 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.
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	18.32 nanograms per milliliter Geometric Coefficient of Variation 42	18.69 nanograms per milliliter Geometric Coefficient of Variation 52	17.83 nanograms per milliliter Geometric Coefficient of Variation 60
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	16.03 nanograms per milliliter Geometric Coefficient of Variation 68	15.2 nanograms per milliliter Geometric Coefficient of Variation 78	14.95 nanograms per milliliter Geometric Coefficient of Variation 86

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=31 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=33 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=32 Participants 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.
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	10.33 micrograms*hour per milliliter Geometric Coefficient of Variation 40	10.13 micrograms*hour per milliliter Geometric Coefficient of Variation 51	10.14 micrograms*hour per milliliter Geometric Coefficient of Variation 56
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	9.051 micrograms*hour per milliliter Geometric Coefficient of Variation 56	8.483 micrograms*hour per milliliter Geometric Coefficient of Variation 68	8.487 micrograms*hour per milliliter Geometric Coefficient of Variation 71

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Ferroquine 400 mg n=31 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=33 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=32 Participants 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.
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	17.81 micrograms*hour per milliliter Geometric Coefficient of Variation 43	16.3 micrograms*hour per milliliter Geometric Coefficient of Variation 63	16.87 micrograms*hour per milliliter Geometric Coefficient of Variation 59
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	20.09 micrograms*hour per milliliter Geometric Coefficient of Variation 48	17.94 micrograms*hour per milliliter Geometric Coefficient of Variation 69	18.32 micrograms*hour per milliliter Geometric Coefficient of Variation 68

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

Adverse Events

Ferroquine 400 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Ferroquine 400 mg + Artefenomel 300 mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Ferroquine 400 mg + Artefenomel 600 mg

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Ferroquine 400 mg + Artefenomel 1000 mg

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ferroquine 400 mg n=35 participants at risk On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 participants at risk 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 participants at risk 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=33 participants at risk 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.
Infections and infestations Malaria	0.00% 0/35 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/36 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	2.8% 1/36 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/33 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.

Other adverse events

Other adverse events
Measure	Ferroquine 400 mg n=35 participants at risk On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 participants at risk 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 participants at risk 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=33 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/35 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	5.6% 2/36 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	2.8% 1/36 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/33 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Blood and lymphatic system disorders Thrombocytopenia	5.7% 2/35 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/36 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/36 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/33 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Gastrointestinal disorders Abdominal pain	2.9% 1/35 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	11.1% 4/36 • Number of events 4 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/36 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	6.1% 2/33 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Gastrointestinal disorders Constipation	0.00% 0/35 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	5.6% 2/36 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/36 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/33 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Gastrointestinal disorders Diarrhoea	0.00% 0/35 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	2.8% 1/36 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/36 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	6.1% 2/33 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Gastrointestinal disorders Nausea	2.9% 1/35 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	2.8% 1/36 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	5.6% 2/36 • Number of events 3 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	6.1% 2/33 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Gastrointestinal disorders Vomiting	8.6% 3/35 • Number of events 3 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	8.3% 3/36 • Number of events 3 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	13.9% 5/36 • Number of events 5 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	30.3% 10/33 • Number of events 10 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
General disorders Pyrexia	0.00% 0/35 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	5.6% 2/36 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	2.8% 1/36 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	12.1% 4/33 • Number of events 4 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Infections and infestations Malaria	20.0% 7/35 • Number of events 7 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	16.7% 6/36 • Number of events 6 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	19.4% 7/36 • Number of events 7 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	18.2% 6/33 • Number of events 6 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Infections and infestations Rhinitis	0.00% 0/35 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	2.8% 1/36 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	5.6% 2/36 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	6.1% 2/33 • Number of events 3 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Nervous system disorders Dizziness	0.00% 0/35 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/36 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	5.6% 2/36 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	12.1% 4/33 • Number of events 4 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Nervous system disorders Headache	8.6% 3/35 • Number of events 3 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	16.7% 6/36 • Number of events 10 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	2.8% 1/36 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	21.2% 7/33 • Number of events 9 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Pruritus	5.7% 2/35 • Number of events 2 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/36 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	0.00% 0/36 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.	3.0% 1/33 • Number of events 1 • From Baseline up to Day 28 Reported AEs were TEAEs, defined as AEs that developed/worsened or became serious during on-treatment phase - defined as the time from the start of the first dose of study drug administration up to Day 28. Analysis was performed on safety population.

Additional Information

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Measure	Ferroquine 400 mg n=35 Participants On Day 0, participants received orally a single dose of FQ 400 mg (4 capsules of 100 mg) in fasted condition.	Ferroquine 400 mg + Artefenomel 300 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 600 mg n=36 Participants 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.	Ferroquine 400 mg + Artefenomel 1000 mg n=33 Participants 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.
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	27.214 nanograms per milliliter Geometric Coefficient of Variation 79.000	21.165 nanograms per milliliter Geometric Coefficient of Variation 55.491	26.599 nanograms per milliliter Geometric Coefficient of Variation 95.999
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 54.030	10.375 nanograms per milliliter Geometric Coefficient of Variation 15.713	6.161 nanograms per milliliter Geometric Coefficient of Variation 9.504	6.805 nanograms per milliliter Geometric Coefficient of Variation 28.203
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	100.569 nanograms per milliliter Geometric Coefficient of Variation 61.578	79.656 nanograms per milliliter Geometric Coefficient of Variation 74.707	97.007 nanograms per milliliter Geometric Coefficient of Variation 72.230
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	29.632 nanograms per milliliter Geometric Coefficient of Variation 49.701	18.377 nanograms per milliliter Geometric Coefficient of Variation 98.310	17.559 nanograms per milliliter Geometric Coefficient of Variation 68.694
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	92.657 nanograms per milliliter Geometric Coefficient of Variation 50.449	84.803 nanograms per milliliter Geometric Coefficient of Variation 75.544	95.062 nanograms per milliliter Geometric Coefficient of Variation 126.388
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	28.098 nanograms per milliliter Geometric Coefficient of Variation 53.438	25.954 nanograms per milliliter Geometric Coefficient of Variation 88.481	20.687 nanograms per milliliter Geometric Coefficient of Variation 70.211
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	82.639 nanograms per milliliter Geometric Coefficient of Variation 49.891	78.196 nanograms per milliliter Geometric Coefficient of Variation 72.454	82.990 nanograms per milliliter Geometric Coefficient of Variation 69.989
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	29.319 nanograms per milliliter Geometric Coefficient of Variation 48.679	25.304 nanograms per milliliter Geometric Coefficient of Variation 78.822	20.299 nanograms per milliliter Geometric Coefficient of Variation 63.388
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 57.540	68.384 nanograms per milliliter Geometric Coefficient of Variation 50.887	59.106 nanograms per milliliter Geometric Coefficient of Variation 70.461	71.743 nanograms per milliliter Geometric Coefficient of Variation 61.238
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	24.385 nanograms per milliliter Geometric Coefficient of Variation 48.408	20.615 nanograms per milliliter Geometric Coefficient of Variation 77.739	18.203 nanograms per milliliter Geometric Coefficient of Variation 64.197
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	53.211 nanograms per milliliter Geometric Coefficient of Variation 48.834	47.568 nanograms per milliliter Geometric Coefficient of Variation 61.373	51.250 nanograms per milliliter Geometric Coefficient of Variation 75.940
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	22.967 nanograms per milliliter Geometric Coefficient of Variation 55.037	19.826 nanograms per milliliter Geometric Coefficient of Variation 70.907	16.763 nanograms per milliliter Geometric Coefficient of Variation 69.091
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	31.161 nanograms per milliliter Geometric Coefficient of Variation 47.829	31.373 nanograms per milliliter Geometric Coefficient of Variation 70.287	29.792 nanograms per milliliter Geometric Coefficient of Variation 76.912
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	20.059 nanograms per milliliter Geometric Coefficient of Variation 45.134	21.315 nanograms per milliliter Geometric Coefficient of Variation 68.366	17.756 nanograms per milliliter Geometric Coefficient of Variation 82.612
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	20.524 nanograms per milliliter Geometric Coefficient of Variation 39.625	21.543 nanograms per milliliter Geometric Coefficient of Variation 63.679	21.322 nanograms per milliliter Geometric Coefficient of Variation 62.951
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 52.300	19.196 nanograms per milliliter Geometric Coefficient of Variation 46.115	20.463 nanograms per milliliter Geometric Coefficient of Variation 55.587	19.108 nanograms per milliliter Geometric Coefficient of Variation 62.123
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 36.770	11.678 nanograms per milliliter Geometric Coefficient of Variation 38.490	12.469 nanograms per milliliter Geometric Coefficient of Variation 48.236	11.263 nanograms per milliliter Geometric Coefficient of Variation 82.611
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	14.797 nanograms per milliliter Geometric Coefficient of Variation 46.036	15.647 nanograms per milliliter Geometric Coefficient of Variation 47.974	13.686 nanograms per milliliter Geometric Coefficient of Variation 72.213
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	7.623 nanograms per milliliter Geometric Coefficient of Variation 28.348	7.601 nanograms per milliliter Geometric Coefficient of Variation 29.047	7.342 nanograms per milliliter Geometric Coefficient of Variation 53.998
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	10.324 nanograms per milliliter Geometric Coefficient of Variation 33.482	10.977 nanograms per milliliter Geometric Coefficient of Variation 34.251	12.014 nanograms per milliliter Geometric Coefficient of Variation 59.403