FALCI: To Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine and Artefenomel in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria

• Sponsor: Sanofi (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02497612
• Collaborator: Medicines for Malaria Venture (Other)
• Enrollment: 377
• Locations: 12
• Arms: 4
• Actual Duration (Months): 50
• Patients Per Site: 31.4
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Primary Objective:

To determine whether a single dose combination of OZ439 (Artefenomel)/FQ (Ferroquine) was an efficacious treatment for uncomplicated Plasmodium falciparum malaria in adults and children.

Secondary Objectives:

• To evaluate the efficacy of OZ439/FQ:

• To determine the incidence of recrudescence and re-infection.

• To determine the time to relief of fever and parasite clearance.

• To evaluate the safety and tolerability of OZ439/FQ in adults and children.

• To characterize the pharmacokinetics of OZ439 in plasma, FQ and its active metabolite SSR97213 in blood.

• To determine the blood/plasma ratio for FQ and SSR97213 in some participants at limited time points in selected sites.

Condition or Disease	Intervention/Treatment	Phase
Plasmodium Falciparum Infection	Drug: Ferroquine SSR97193; Drug: Artefenomel; Other: Placebo	Phase 2

Detailed Description

Total duration was 63 days for each participant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 377 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine (FQ) With Artefenomel (OZ439) in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
• Actual Study Start Date: Jul 25, 2015
• Actual Primary Completion Date: Sep 23, 2019
• Actual Study Completion Date: Sep 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) On Day 0, based on the body weight (BW), participants received orally a single dose of ferroquine (FQ) capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of artefenomel (OZ439) (maximum dose up to 800 milligrams [mg]) oral suspension as follows: BW greater than or equal to (>=) 35 kilograms (kg): FQ 400 mg + OZ439 800 mg; BW >=24 kg to less than (<) 35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	Drug: Ferroquine SSR97193; Pharmaceutical form:Capsules Route of administration: oral; Drug: Artefenomel; Pharmaceutical form:Granules for suspension Route of administration: oral; Other: Placebo; Capsules. Placebo capsules were used to keep the same number of capsules in each weight band while keeping the ferroquine dose blinded. No participant received placebo only.
Experimental: Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	Drug: Ferroquine SSR97193; Pharmaceutical form:Capsules Route of administration: oral; Drug: Artefenomel; Pharmaceutical form:Granules for suspension Route of administration: oral; Other: Placebo; Capsules. Placebo capsules were used to keep the same number of capsules in each weight band while keeping the ferroquine dose blinded. No participant received placebo only.
Experimental: Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	Drug: Ferroquine SSR97193; Pharmaceutical form:Capsules Route of administration: oral; Drug: Artefenomel; Pharmaceutical form:Granules for suspension Route of administration: oral; Other: Placebo; Capsules. Placebo capsules were used to keep the same number of capsules in each weight band while keeping the ferroquine dose blinded. No participant received placebo only.
Experimental: Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.	Drug: Ferroquine SSR97193; Pharmaceutical form:Capsules Route of administration: oral; Drug: Artefenomel; Pharmaceutical form:Granules for suspension Route of administration: oral; Other: Placebo; Capsules. Placebo capsules were used to keep the same number of capsules in each weight band while keeping the ferroquine dose blinded. No participant received placebo only.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28: African <=5 Years Per Protocol Population at Day 28 (PP28) [Day 28]

   ACPR: negative parasitemia at Day 28, irrespective of axillary temperature(AT), in participants not meeting any criteria of early therapy failure (ETF):Danger signs (DS)/severe malaria (SM) at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count >Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5 degree Celsius (°C); or parasite 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; or presence of parasitemia and AT>=37.5°C between Day 4 and 28, or late parasitological failure (LPF):presence of parasitemia between Day 7 and 28 and AT<37.5°C or having rescue therapy for malaria. PCR-adjusted 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. In data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.

Secondary Outcome Measures

1. Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: African >5 Years Per Protocol Population at Day 28 (A5PP28) [Day 28]

   ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.

2. Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: Asian PP Population at Day 28 (APP28) [Day 28]

   ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.

3. Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP Population at Day 42 (PP42) [Day 42]

   ACPR: negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT >=37.5°C between Day 4 and 42, or LPF: presence of parasitemia between Day 7 and 42 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.

4. Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP Population at Day 63 (PP63) [Day 63]

   ACPR: negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT >=37.5°C between Day 4 and 63, or LPF: presence of parasitemia between Day 7 and 63 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.

5. Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28: African <=5 Years PP28 Population [Day 28]

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

6. Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP42 Population [Day 42]

   ACPR was defined as negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT >=37.5°C between Day 4 and 42 or, LPF: presence of parasitemia between Day 7 and 42 and AT <37.5°C or having rescue therapy for malaria PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.

7. Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP63 Population [Day 63]

   Crude ACPR was defined as negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT >=37.5°C between Day 4 and 63 or, LPF: presence of parasitemia between Day 7 and 63 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.

8. Time to Re-emergence [Up to Day 63]

   Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Re-emergence was confirmed by microscopy (positive blood smear). Kaplan-Maier method was used for estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.

9. Time to Recrudescence [Up to Day 63]

   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. Kaplan-Maier method was used for estimation.

10. Time to Re-infection [Up to Day 63]

    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 differs from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.

11. Parasite Clearance Time (PCT): African <=5 Years PP Population [From the start of study drug administration up to the time of the first negative film (up to Day 63)]

    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). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, in the data table "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.

12. Parasite Clearance Time: African >5 Years PP Population [From the start of study drug administration up to the time of the first negative film (up to Day 63)]

    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). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.

13. Parasite Clearance Time: Asian PP Population [From the start of study drug administration up to the time of the first negative film (up to Day 63)]

    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). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.

14. Fever Clearance Time (FCT): African <=5 Years PP Population [From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)]

    FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first assessment. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.

15. Fever Clearance Time: African >5 Years PP Population [From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)]

    FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.

16. Fever Clearance Time: Asian PP Population [From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)]

    FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.

17. Parasite Reduction Ratio (PRRlog10) at 24 Hours and 48 Hours: African <=5 Years PP Population [24 and 48 hours post dose]

    The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.

18. Parasite Reduction Ratio at 24 Hours and 48 Hours: African >5 Years PP Population [24 and 48 hours post dose]

    The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.

19. Parasite Reduction Ratio at 24 Hours and 48 Hours: Asian PP Population [24 and 48 hours post dose]

    The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.

20. 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 63]

    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 the first dose of double-blind drug administration up to the Day 63. 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.

21. Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Artefenomel [2, 4, 6, 12, 24, 48, 72 and 672 hours post dose]

    Cmax is the maximum observed plasma concentration of artefenomel.

22. Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Artefenomel [2, 4, 6, 12, 24, 48, 72 and 672 hours post dose]

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

23. Pharmacokinetics (PK): Apparent Total Clearance of Artefenomel From Plasma After Oral Administration [2, 4, 6, 12, 24, 48, 72 and 672 hours post dose]

    Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.

24. Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration (Vss/F) of Artefenomel [2, 4, 6, 12, 24, 48, 72 and 672 hours post dose]

    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

25. Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine (Cmax) [2, 4, 6, 12, 24, 48, 72 and 672 hours post dose]

    Cmax is the maximum observed plasma concentration of Ferroquine.

26. Pharmacokinetics: Area Under the Curve From Time 0 to Day 28 (AUC0-day28) of Ferroquine [2, 4, 6, 8, 12, 24, 48, 168, 336 and 672 hours postdose]

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

27. Pharmacokinetics: Apparent Total Clearance of Ferroquine From Plasma After Oral Administration [2, 4, 6, 12, 24, 48, 72 and 672 hours post dose]

    Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.

28. Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration of Ferroquine [2, 4, 6, 12, 24, 48, 72 and 672 hours post dose]

    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

29. Pharmacokinetics: Blood/Plasma Ratio for Ferroquine and Its Active Metabolite SSR97213 [2, 4, 6, 12, 24, 48, 72 and 672 hours post dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

Male or female participant aged greater than (>) 6 months old and <70 years old:

• Cohort 1 = 14 years < age <70 years and body weight greater than or equal to (>=) 35 kilogram (kg).

• Cohort 2 = 5 years < age less than or equal to (<=) 14 years.

• Cohort 3 = 2 years < age <=5 years.

• Cohort 4 = 6 months < age <=2 years.

Body weight >=5 kg and <=90 kg.

Presence of mono-infection by Plasmodium falciparum with:

• Fever, as defined by axillary temperature >=37.5 degrees Celsius (°C) or oral/rectal/tympanic temperature >=38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,

• Microscopically (blood smear) confirmed parasite infection, ranging from 1000 to 100 000 asexual parasites/microliter of blood.

Informed consent form signed by the participant or by the legally acceptable representative of the minor participant.

Exclusion criteria:

Presence of severe malaria.

Anti-malarial treatment:

• With piperaquine-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine (SP) within the previous 6 weeks (after their inhibition of new infections had fallen below 50%).

• 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.

Known history or evidence of clinically significant disorders.

Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest which are: P-glycoprotein substrates, Cytochrome P450 (CYP) 2D6 main substrates and/or strong CYP2C or CYP3A inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers.

Mixed plasmodium infection.

Severe vomiting.

Severe malnutrition.

Laboratory parameters with clinically significant abnormalities and/or reaching critical values. For Liver Function Test. Aspartate aminotransferase (>2 [upper limit of normal] ULN), or alanine aminotransferase (>2 ULN) or total bilirubin >1.5 ULN.

Presence of Hepatitis A Immunoglobulin M, Hepatitis B surface antigen or Hepatitis C antibody.

Had received an investigational drug within the past 4 weeks.

Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance.

Measles and yellow fever vaccine injection within the last 15 days and or planned for the 28 days after randomization.

Female participant of child bearing potential not willing to use an effective contraceptive(s) method(s) for the duration of the study.

Positive serum or urine beta-human chorionic gonadotropin pregnancy test at study screening for female participants of childbearing potential.

Breastfeeding women.

Male participant having a partner of child bearing potential not willing to use an effective method of birth control during the study treatment period.

Splenectomized participants or presence of surgical scar on left hypochondrium. Participant unable to drink.

Known history of hypersensitivity, allergic or anaphylactoid reactions to ferroquine or other amino-quinolines or to OZ439 or OZ277 or to any of the excipients.

Family history of sudden death or of congenital prolongation of the Corrected QT (QTc) interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval e.g., participants with a history of symptomatic cardiac arrhythmias or with clinically relevant bradycardia.

QTc using Fridericia's formula >450 millisecond 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.

Any treatment known to induce a lengthening of QT interval.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 204001	Cotonou		Benin
2	Investigational Site Number 854002	Comoé		Burkina Faso
3	Investigational Site Number 854003	Niangoloko		Burkina Faso
4	Investigational Site Number 854001	Ouagadougou		Burkina Faso
5	Investigational Site Number 266002	Lambaréné		Gabon
6	Investigational Site Number 266001	Libreville		Gabon
7	Investigational Site Number 404003	Kisumu		Kenya
8	Investigational Site Number 404002	Siaya		Kenya
9	Investigational Site Number 508001	Chokwé		Mozambique
10	Investigational Site Number 800002	Tororo		Uganda
11	Investigational Site Number 704003	Binh Phuoc		Vietnam
12	Investigational Site Number 704004	Gia Lai		Vietnam

Sponsors and Collaborators

• Sanofi
• Medicines for Malaria Venture

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Apr 10, 2019
• Statistical Analysis Plan - Dec 19, 2019

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02497612
• Other Study ID Numbers: DRI12805; U1111-1155-7960
• First Posted: Jul 14, 2015
• Last Update Posted: Mar 24, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Malaria; Malaria, Falciparum; Artefenomel; Ferroquine

Study Results

Participant Flow

Recruitment Details	Study conducted at 12 active sites in 7 countries. Total of 806 participants were screened between 25 July 2015 and 22 July 2019, of which 377 were randomized to 1 of 4 treatment arms (via Integrated Web Recognition System using permuted block randomization schedules). 429 participants failed screening mainly due to meeting exclusion criteria.
Pre-assignment Detail	In each arm, participants were divided in 4 cohorts (C):C1 (greater than [>] 14 years (yrs) to less than [<] 70 yrs); C2 (>5 yrs to less than or equal to [<=] 14 yrs );C3 (>2 yrs to <=5 yrs); C4 (>6 months to <=2 yrs). Day 0 (drug administration day, per protocol) was Day 1 for safety reporting as per Clinical Data Interchange Standards Consortium.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the body weight (BW), participants received orally a single dose of ferroquine (FQ) capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of artefenomel (OZ439) (maximum dose up to 800 milligrams [mg]) oral suspension as follows: BW greater than or equal to (>=) 35 kilograms (kg): FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Period Title: Overall Study
STARTED	93	94	97	93
Treated	92	94	96	91
Cohort 1: >14 Years to <70 Years	14	15	18	16
Cohort 2: >5 Years to <=14 Years	6	5	6	5
Cohort 3: >2 Years to <=5 Years	66	66	67	65
Cohort 4: >6 Months to <=2 Years	7	8	6	7
COMPLETED	27	37	48	46
NOT COMPLETED	66	57	49	47

Baseline Characteristics

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)	Total
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg	Total of all reporting groups
Overall Participants	93	94	97	93	377
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.34 (9.94)	6.97 (8.97)	7.61 (9.60)	7.68 (10.44)	7.40 (9.71)
Age, Customized (Count of Participants)
>6 months to <=2 years	7 7.5%	8 8.5%	6 6.2%	7 7.5%	28 7.4%
>2 to <=5 years	66 71%	66 70.2%	67 69.1%	65 69.9%	264 70%
>5 to <=14 years	6 6.5%	5 5.3%	6 6.2%	5 5.4%	22 5.8%
>14 to <18 years	6 6.5%	5 5.3%	7 7.2%	4 4.3%	22 5.8%
>=18 years	8 8.6%	10 10.6%	11 11.3%	12 12.9%	41 10.9%
Sex: Female, Male (Count of Participants)
Female	37 39.8%	46 48.9%	43 44.3%	56 60.2%	182 48.3%
Male	56 60.2%	48 51.1%	54 55.7%	37 39.8%	195 51.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	4 4.3%	5 5.3%	6 6.2%	6 6.5%	21 5.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	89 95.7%	89 94.7%	91 93.8%	87 93.5%	356 94.4%
White	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28: African <=5 Years Per Protocol Population at Day 28 (PP28)
Description	ACPR: negative parasitemia at Day 28, irrespective of axillary temperature(AT), in participants not meeting any criteria of early therapy failure (ETF):Danger signs (DS)/severe malaria (SM) at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count >Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5 degree Celsius (°C); or parasite 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; or presence of parasitemia and AT>=37.5°C between Day 4 and 28, or late parasitological failure (LPF):presence of parasitemia between Day 7 and 28 and AT<37.5°C or having rescue therapy for malaria. PCR-adjusted 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. In data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

African <=5 years PP28: participants with parasitologically confirmed Plasmodium falciparum malaria at screening/baseline, received the single administration of OZ439/FQ, without major protocol violations impacting efficacy, evaluable for crude ACPR at Day 28, excluding those who received rescue treatment due to vomiting during drug administration.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	51	60	57	60
Number (95% Confidence Interval) [percentage of participants]	78.4 84.3%	85.0 90.4%	89.5 92.3%	91.7 98.6%

2. Secondary Outcome

Title	Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: African >5 Years Per Protocol Population at Day 28 (A5PP28)
Description	ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

African >5 years PP28: participants with parasitologically confirmed Plasmodium falciparum malaria at screening/baseline, received the single administration of OZ439/FQ, without major protocol violations impacting efficacy, evaluable for crude ACPR at Day 28, excluding those who received rescue treatment due to vomiting during drug administration.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	11	10	12	10
Number (95% Confidence Interval) [percentage of participants]	72.7 78.2%	100 106.4%	100 103.1%	90.0 96.8%

3. Secondary Outcome

Title	Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: Asian PP Population at Day 28 (APP28)
Description	ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Asian PP28 population: participants with parasitologically confirmed Plasmodium falciparum malaria at screening/baseline, received the single administration of OZ439/FQ, without major protocol violations impacting efficacy, evaluable for crude ACPR at Day 28, excluding those who received rescue treatment due to vomiting during drug administration.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	4	4	5	5
Number (95% Confidence Interval) [percentage of participants]	25.0 26.9%	25.0 26.6%	40.0 41.2%	20.0 21.5%

4. Secondary Outcome

Title	Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP Population at Day 42 (PP42)
Description	ACPR: negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT >=37.5°C between Day 4 and 42, or LPF: presence of parasitemia between Day 7 and 42 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

African <=5 years PP42: participants with parasitologically confirmed Plasmodium falciparum malaria at screening/baseline, received the single administration of OZ439/FQ, without major protocol violations impacting efficacy, evaluable for crude ACPR at Day 42, excluding those who received rescue treatment due to vomiting during drug administration.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	43	55	50	57
Number (95% Confidence Interval) [percentage of participants]	69.8 75.1%	81.8 87%	84.0 86.6%	87.7 94.3%

5. Secondary Outcome

Title	Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP Population at Day 63 (PP63)
Description	ACPR: negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT >=37.5°C between Day 4 and 63, or LPF: presence of parasitemia between Day 7 and 63 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame	Day 63

Outcome Measure Data

Analysis Population Description

African <=5 years PP63: participants with parasitologically confirmed Plasmodium falciparum malaria at screening/baseline, received the single administration of OZ439/FQ, without major protocol violations impacting efficacy, evaluable for crude ACPR at Day 63, excluding those who received rescue treatment due to vomiting during drug administration.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	39	43	44	47
Number (95% Confidence Interval) [percentage of participants]	64.1 68.9%	76.7 81.6%	81.8 84.3%	87.2 93.8%

6. Secondary Outcome

Title	Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28: African <=5 Years PP28 Population
Description	ACPR was defined as negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28 or, LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish re-infection (new clone of parasite) or recrudescence.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Analysis was performed on African <=5 years PP28 population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	69	67	63	62
Number (95% Confidence Interval) [percentage of participants]	49.3 53%	71.6 76.2%	76.2 78.6%	87.1 93.7%

7. Secondary Outcome

Title	Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP42 Population
Description	ACPR was defined as negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT >=37.5°C between Day 4 and 42 or, LPF: presence of parasitemia between Day 7 and 42 and AT <37.5°C or having rescue therapy for malaria PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

Analysis was performed on African <=5 years PP42 population.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	69	65	59	61
Number (95% Confidence Interval) [percentage of participants]	39.1 42%	50.8 54%	61.0 62.9%	68.9 74.1%

8. Secondary Outcome

Title	Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP63 Population
Description	Crude ACPR was defined as negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT >=37.5°C between Day 4 and 63 or, LPF: presence of parasitemia between Day 7 and 63 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
Time Frame	Day 63

Outcome Measure Data

Analysis Population Description

Analysis was performed on African <=5 years PP63 population.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	68	65	59	60
Number (95% Confidence Interval) [percentage of participants]	35.3 38%	46.2 49.1%	57.6 59.4%	58.3 62.7%

9. Secondary Outcome

Title	Time to Re-emergence
Description	Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Re-emergence was confirmed by microscopy (positive blood smear). Kaplan-Maier method was used for estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame	Up to Day 63

Outcome Measure Data

Analysis Population Description

African <=5 years modified Intent-To-Treat (mITT) population: all randomized African participants <=5 years with parasitological confirmed Plasmodium falciparum (P. falciparum) malaria at baseline, who received the single administration of OZ439/FQ and excluding participants who required rescue treatment due to vomiting during drug administration.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	69	73	70	69
Median (95% Confidence Interval) [days]	36.0	61.0	NA	64.0

10. Secondary Outcome

Title	Time to Recrudescence
Description	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. Kaplan-Maier method was used for estimation.
Time Frame	Up to Day 63

Outcome Measure Data

Analysis Population Description

Analysis was performed on African <=5 years mITT population. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	69	73	70	69
Median (95% Confidence Interval) [days]	NA	NA	NA	NA

11. Secondary Outcome

Title	Time to Re-infection
Description	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 differs from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.
Time Frame	Up to Day 63

Outcome Measure Data

Analysis Population Description

Analysis was performed on African <=5 years mITT population. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	69	73	70	69
Median (95% Confidence Interval) [days]	NA	NA	NA	65.0

12. Secondary Outcome

Title	Parasite Clearance Time (PCT): African <=5 Years PP Population
Description	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). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, in the data table "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame	From the start of study drug administration up to the time of the first negative film (up to Day 63)

Outcome Measure Data

Analysis Population Description

African<=5years PP population participants with parasitologically confirmed P.falciparum malaria at screening/baseline, received the single administration of OZ439/FQ, without major protocol violation impacting efficacy, evaluable for crude ACPR at pre-defined time point, excluding who had rescue treatment due to vomiting during drug administration

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	69	67	63	62
Median (95% Confidence Interval) [hours]	36.0	36.0	36.1	36.1

13. Secondary Outcome

Title	Parasite Clearance Time: African >5 Years PP Population
Description	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). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame	From the start of study drug administration up to the time of the first negative film (up to Day 63)

Outcome Measure Data

Analysis Population Description

African >5years PP population participants with parasitologically confirmed P.falciparum malaria at screening/baseline, received the single administration of OZ439/FQ, without major protocol violation impacting efficacy, evaluable for crude ACPR at pre-defined time point, excluding who had rescue treatment due to vomiting during drug administration

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	11	11	12	10
Median (95% Confidence Interval) [hours]	24.0	24.3	24.3	27.2

14. Secondary Outcome

Title	Parasite Clearance Time: Asian PP Population
Description	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). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame	From the start of study drug administration up to the time of the first negative film (up to Day 63)

Outcome Measure Data

Analysis Population Description

Asian PP population: participants with parasitologically confirmed P.falciparum malaria at screening/baseline, received the single administration of OZ439/FQ, without major protocol violations impacting efficacy, evaluable for crude ACPR at pre-defined time point, excluding who had rescue treatment due to vomiting during drug administration.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	4	5	5	5
Median (95% Confidence Interval) [hours]	82.0	75.1	79.8	72.2

15. Secondary Outcome

Title	Fever Clearance Time (FCT): African <=5 Years PP Population
Description	FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first assessment. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
Time Frame	From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)

Outcome Measure Data

Analysis Population Description

Analyzed performed on African <=5 years PP population participants with fever and did not receive paracetamol within 96 hours of study drug administration. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had event, plus those who were censored.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	5	3	4	4
Median (95% Confidence Interval) [hours]	1.0	1.0	1.0	1.0

16. Secondary Outcome

Title	Fever Clearance Time: African >5 Years PP Population
Description	FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
Time Frame	From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)

Outcome Measure Data

Analysis Population Description

Analysis was performed on African >5 years PP population participants with fever and did not receive paracetamol within 96 hours of study drug administration. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had event, plus those who were censored.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	3	1	2	1
Median (95% Confidence Interval) [hours]	1.0	1.0	1.5	2.0

17. Secondary Outcome

Title	Fever Clearance Time: Asian PP Population
Description	FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame	From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Asian PP population participants with fever and did not receive paracetamol within 96 hours of study drug administration. Here, '0' in "overall number of participants analyzed"=no participants were evaluable since they had paracetamol within 96 hours of study drug administration.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	1	0	0	1
Median (95% Confidence Interval) [hours]	18.0	36.0

18. Secondary Outcome

Title	Parasite Reduction Ratio (PRRlog10) at 24 Hours and 48 Hours: African <=5 Years PP Population
Description	The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Time Frame	24 and 48 hours post dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on African <=5 years PP population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	63	57	58	53
PRR24 (log10)	2.867	3.011	2.397	2.587
PRR48 (log10)	5.734	6.023	4.794	5.174

19. Secondary Outcome

Title	Parasite Reduction Ratio at 24 Hours and 48 Hours: African >5 Years PP Population
Description	The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Time Frame	24 and 48 hours post dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on African >5 years PP population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	7	9	10	8
PRR24 (log10)	2.979	4.069	3.288	3.054
PRR48 (log10)	5.957	8.137	6.577	6.108

20. Secondary Outcome

Title	Parasite Reduction Ratio at 24 Hours and 48 Hours: Asian PP Population
Description	The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Time Frame	24 and 48 hours post dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	4	5	4	4
PRR24 (log10)	1.167	1.125	1.688	1.353
PRR48 (log10)	2.335	2.250	3.377	2.705

21. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)
Description	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 the first dose of double-blind drug administration up to the Day 63. 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 63

Outcome Measure Data

Analysis Population Description

Analyzed on safety population which included all randomized participants who received at least 1 dose or part of a dose of the study medication.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	92	94	96	91
Any TEAE	84 90.3%	87 92.6%	85 87.6%	81 87.1%
Any treatment-emergent SAE	0 0%	2 2.1%	4 4.1%	2 2.2%
Any treatment-emergent AESI	5 5.4%	8 8.5%	9 9.3%	11 11.8%
Any TEAE led to treatment discontinuation	3 3.2%	2 2.1%	3 3.1%	2 2.2%
Any TEAE led to death	0 0%	0 0%	0 0%	0 0%

22. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Artefenomel
Description	Cmax is the maximum observed plasma concentration of artefenomel.
Time Frame	2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PK population for OZ439 which included all participants who received OZ439 and had at least one evaluable blood sample for PK and with adequate documentation of dosing date and sampling date.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	88	93	93	90
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter]	1072 (95)	936.7 (91)	771.8 (92)	797.8 (119)

23. Secondary Outcome

Title	Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Artefenomel
Description	Area under the plasma concentration versus time curve from time zero to infinity.
Time Frame	2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population for OZ439.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	88	93	93	90
Geometric Mean (Geometric Coefficient of Variation) [micrograms*hour per milliliter]	14.24 (124)	12.41 (127)	9.621 (130)	9.605 (147)

24. Secondary Outcome

Title	Pharmacokinetics (PK): Apparent Total Clearance of Artefenomel From Plasma After Oral Administration
Description	Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame	2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Outcome Measure Data

Analysis Population Description

Focus of PK assessment was to support the analysis of exposure versus efficacy relationship (PK and pharmacodynamic [PD]). Since clearance was considered irrelevant to the objective of the PK and exposure-response analyses, therefore data for this outcome measure were not collected and reported.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	0	0	0	0

25. Secondary Outcome

Title	Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration (Vss/F) of Artefenomel
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame	2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	0	0	0	0

26. Secondary Outcome

Title	Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine (Cmax)
Description	Cmax is the maximum observed plasma concentration of Ferroquine.
Time Frame	2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PK population for FQ which included all participants who received FQ and had at least one evaluable blood sample for PK and with adequate documentation of dosing date and sampling date. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	88	93	93	90
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter]	148.1 (52)	222.8 (66)	350 (55)	467.6 (80)

27. Secondary Outcome

Title	Pharmacokinetics: Area Under the Curve From Time 0 to Day 28 (AUC0-day28) of Ferroquine
Description	Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours).
Time Frame	2, 4, 6, 8, 12, 24, 48, 168, 336 and 672 hours postdose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	88	93	93	90
Geometric Mean (Geometric Coefficient of Variation) [micrograms*hour per milliliter]	14.92 (40)	22.56 (48)	33.84 (48)	46.4 (52)

28. Secondary Outcome

Title	Pharmacokinetics: Apparent Total Clearance of Ferroquine From Plasma After Oral Administration
Description	Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame	2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	0	0	0	0

29. Secondary Outcome

Title	Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration of Ferroquine
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame	2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	0	0	0	0

30. Secondary Outcome

Title	Pharmacokinetics: Blood/Plasma Ratio for Ferroquine and Its Active Metabolite SSR97213
Time Frame	2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Outcome Measure Data

Analysis Population Description

Focus of PK assessment was to support the analysis of exposure versus efficacy relationship (PK and PD). Since blood plasma ratio of active drug and metabolite was considered irrelevant to the objective of the PK and exposure-response analyses, therefore data for this outcome measure were not collected and reported.

Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)	Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Measure Participants	0	0	0	0

Adverse Events

Time Frame	From Baseline up to Day 63
Adverse Event Reporting Description	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 double-blind drug administration up to Day 63. Analysis was performed on safety population.
Arm/Group Title	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm/Group Description	On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg oral suspension as follows: BW >= 35 kg: FQ 400 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.		On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.		On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.		On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
All Cause Mortality
	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/92 (0%)		0/94 (0%)		0/96 (0%)		0/91 (0%)
Serious Adverse Events
	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/92 (0%)		2/94 (2.1%)		4/96 (4.2%)		2/91 (2.2%)
Hepatobiliary disorders
Drug-Induced Liver Injury	0/92 (0%)	0	0/94 (0%)	0	1/96 (1%)	1	0/91 (0%)	0
Infections and infestations
Malaria	0/92 (0%)	0	1/94 (1.1%)	1	1/96 (1%)	1	0/91 (0%)	0
Hepatitis A	0/92 (0%)	0	0/94 (0%)	0	0/96 (0%)	0	1/91 (1.1%)	1
Pharyngitis	0/92 (0%)	0	1/94 (1.1%)	1	0/96 (0%)	0	0/91 (0%)	0
Investigations
Alanine Aminotransferase Increased	0/92 (0%)	0	0/94 (0%)	0	2/96 (2.1%)	2	0/91 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration	0/92 (0%)	0	0/94 (0%)	0	0/96 (0%)	0	1/91 (1.1%)	1
Other (Not Including Serious) Adverse Events
	Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)		Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/92 (83.7%)		79/94 (84%)		77/96 (80.2%)		74/91 (81.3%)
Gastrointestinal disorders
Vomiting	27/92 (29.3%)	29	27/94 (28.7%)	28	34/96 (35.4%)	37	34/91 (37.4%)	37
Diarrhoea	10/92 (10.9%)	10	11/94 (11.7%)	12	7/96 (7.3%)	9	11/91 (12.1%)	13
Abdominal Pain	7/92 (7.6%)	7	5/94 (5.3%)	5	5/96 (5.2%)	5	6/91 (6.6%)	6
General disorders
Pyrexia	7/92 (7.6%)	9	2/94 (2.1%)	3	9/96 (9.4%)	12	10/91 (11%)	10
Infections and infestations
Malaria	55/92 (59.8%)	75	50/94 (53.2%)	65	40/96 (41.7%)	49	41/91 (45.1%)	45
Upper Respiratory Tract Infection	7/92 (7.6%)	9	6/94 (6.4%)	8	17/96 (17.7%)	18	10/91 (11%)	10
Bronchitis	3/92 (3.3%)	3	5/94 (5.3%)	5	4/96 (4.2%)	4	5/91 (5.5%)	5
Rhinitis	4/92 (4.3%)	4	3/94 (3.2%)	4	1/96 (1%)	1	7/91 (7.7%)	8
Investigations
Electrocardiogram Qt Prolonged	6/92 (6.5%)	6	5/94 (5.3%)	5	6/96 (6.3%)	7	8/91 (8.8%)	8
Metabolism and nutrition disorders
Decreased Appetite	5/92 (5.4%)	6	8/94 (8.5%)	8	5/96 (5.2%)	5	5/91 (5.5%)	5
Nervous system disorders
Headache	6/92 (6.5%)	6	7/94 (7.4%)	8	7/96 (7.3%)	8	5/91 (5.5%)	6
Respiratory, thoracic and mediastinal disorders
Cough	10/92 (10.9%)	13	7/94 (7.4%)	9	15/96 (15.6%)	16	15/91 (16.5%)	17

Limitations/Caveats

The study was terminated early because all treatment arms met the futility criteria for efficacy during the pre-planned interim analysis. On 02-August-2018, recruitment in Asia was stopped due to lack of efficacy.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.