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
- Conditions
- Plasmodium Falciparum Infection
- Interventions
- Registration Number
- NCT02497612
- Lead Sponsor
- Sanofi
- 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.
- Detailed Description
Total duration was 63 days for each participant.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 377
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) Ferroquine SSR97193 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. Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) Placebo 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. Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) Ferroquine SSR97193 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. Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) Placebo 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. Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) Ferroquine SSR97193 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. Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) Ferroquine SSR97193 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. Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) Placebo 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. Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) Placebo 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. Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg) Artefenomel 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. Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg) Artefenomel 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. Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg) Artefenomel 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. Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg) Artefenomel 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
Pharmacokinetics: Blood/Plasma Ratio for Ferroquine and Its Active Metabolite SSR97213 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Trial Locations
- Locations (12)
Investigational Site Number 854001
🇧🇫Ouagadougou, Burkina Faso
Investigational Site Number 266001
🇬🇦Libreville, Gabon
Investigational Site Number 704003
🇻🇳Binh Phuoc, Vietnam
Investigational Site Number 800002
🇺🇬Tororo, Uganda
Investigational Site Number 204001
🇧🇯Cotonou, Benin
Investigational Site Number 854002
🇧🇫Comoé, Burkina Faso
Investigational Site Number 854003
🇧🇫Niangoloko, Burkina Faso
Investigational Site Number 404003
🇰🇪Kisumu, Kenya
Investigational Site Number 266002
🇬🇦Lambaréné, Gabon
Investigational Site Number 404002
🇰🇪Siaya, Kenya
Investigational Site Number 508001
🇲🇿Chokwé, Mozambique
Investigational Site Number 704004
🇻🇳Gia Lai, Vietnam