Compounds > ferroquine
Page last updated: 2024-10-15

ferroquine

Description

ferroquine: an antimalarial agent; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID140118553
MeSH IDM0456809

Synonyms (10)

Synonym
185055-67-8
ssr97193
ssr-97193
8d81js19et ,
ssr 97193
ferroquine
ferrochloroquine
7-chloro-n-[[2-[(dimethylamino)methyl]cyclopenta-2,4-dien-1-yl]methyl]quinolin-4-amine;cyclopenta-1,3-diene;iron(2+)
ferroquina
ferroquinum

Research Excerpts

Overview

Ferroquine (FQ) is a 4-aminoquinoline antimalarial which contains a quinoline nucleus similar to chloroquine, but a novel ferrocenic group in its side chain. It shows good activity in vitro and in animal models, but development of cross-resistance is of concern.

ExcerptReference
"Ferroquine is a derivative of chloroquine with antimalarial properties."( Ferroquine and its derivatives: new generation of antimalarial agents.
Baig, U; Hun, LT; Jameel, E; Mumtazuddin, S; Wani, WA, 2015)
"Ferroquine is a new combination partner for fast-acting ACTs such as artesunate."( Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study.
Abdallah, AM; Bonkian, LN; Bouyou-Akotet, M; Cantalloube, C; Coulibaly, B; Din-Bell, C; Djeriou, E; Held, J; Kimutai, R; Koiwai, K; Kombila, M; Kremsner, PG; Lell, B; Mordmüller, B; Moulero, B; Nahum, A; Otieno, L; Otsyula, N; Salazar, CL; Sié, A; Siribie, M; Sirima, SB; Supan, C; Ter-Minassian, D; Tinto, H; Waitumbi, J, 2015)
"Ferroquine (SSR97193) is a candidate anti-malarial currently undergoing clinical trials for malaria. "( A Phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study.
Baker, M; Cantalloube, C; Djeriou, E; Griffin, P; Hooft van Huijsduijnen, R; Marquart, L; McCarthy, JS; Möhrle, JJ; O'Rourke, P; Rückle, T; Ter-Minassian, D, 2016)
"Ferroquine is a ferrocenic derivative of chloroquine with proven anti-malarial activity against chloroquine-resistant and -sensitive P."( Phase I randomized dose-ascending placebo-controlled trials of ferroquine--a candidate anti-malarial drug--in adults with asymptomatic Plasmodium falciparum infection.
Dal-Bianco, MP; Issifou, S; Kombila, M; Kremsner, PG; Lell, B; Matsiegui, PB; Missinou, MA; Mombo-Ngoma, G; Ospina Salazar, CL; Ramharter, M; Supan, C; Ter-Minassian, D, 2011)
"Ferroquine (FQ) is a 4-aminoquinoline antimalarial which contains a quinoline nucleus similar to chloroquine, but a novel ferrocenic group in its side chain. "( Insights into the mechanism of action of ferroquine. Relationship between physicochemical properties and antiplasmodial activity.
Basilico, N; Biot, C; Boyce, M; Brocard, JS; Egan, TJ; Forfar-Bares, I; Maciejewski, LA; Nowogrocki, G; Olliaro, P; Taramelli, D, )
"Ferroquine is a derivative of chloroquine and shows good activity in vitro and in animal models, but the development of cross-resistance is of concern."( In vitro activity of ferroquine (SAR97193) is independent of chloroquine resistance in Plasmodium falciparum.
Dietz, K; Kreidenweiss, A; Kremsner, PG; Mordmüller, B, 2006)
"Ferroquine (SSR97193) is a new 4-aminoquinoline antimalarial active against chloroquine resistant and sensitive P."( In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border.
Barends, M; Jaidee, A; Khaohirun, N; Nosten, F; Singhasivanon, P, 2007)

Effects

ExcerptReference
"Ferroquine has a potent ex vivo effect on P."( Plasmodium vivax susceptibility to ferroquine.
Barends, M; Jaidee, A; Kaewpongsri, S; Leimanis, ML; Nosten, F; Phyo, AP; Renia, L; Russell, B; Sriprawat, K; Suwanarusk, R, 2010)
"Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. "( In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models and antimalarial activity of major metabolites on Plasmodium falciparum.
Biot, C; Bourrié, M; Brocard, J; Daher, W; Dive, D; Fabre, G; Fraisse, L; Guillou, F; Khalife, J; Klieber, S; Maffrand, JP; Meunier, V; Pelinski, L; Sadoun, F, 2006)

Toxicity

ExcerptReference
" Safety was determined by recording adverse events and monitoring clinical laboratory assessments during the course of the study."( A Phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study.
Baker, M; Cantalloube, C; Djeriou, E; Griffin, P; Hooft van Huijsduijnen, R; Marquart, L; McCarthy, JS; Möhrle, JJ; O'Rourke, P; Rückle, T; Ter-Minassian, D, 2016)

Pharmacokinetics

ExcerptReference
" This study characterizes its pharmacokinetic properties."( Pharmacokinetics of ferroquine, a novel 4-aminoquinoline, in asymptomatic carriers of Plasmodium falciparum infections.
Biot, C; Dal-Bianco, MP; Filali-Ansary, A; Issifou, S; Kremsner, PG; Lell, B; Mazuir, F; Mombo-Ngoma, G; Ospina Salazar, CL; Ramharter, M; Supan, C; Ter-Minassian, D, 2012)

Dosage Studied

ExcerptReference
" PK/PD modelling resulted in a predicted minimal parasiticidal concentration of 20 ng/mL, and the single dosing tested in this study was predicted to maintain an exposure above this threshold for 454 h (37."( A Phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study.
Baker, M; Cantalloube, C; Djeriou, E; Griffin, P; Hooft van Huijsduijnen, R; Marquart, L; McCarthy, JS; Möhrle, JJ; O'Rourke, P; Rückle, T; Ter-Minassian, D, 2016)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (55)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's13 (23.64)29.6817
2010's32 (58.18)24.3611
2020's10 (18.18)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials7 (12.07%)5.53%
Reviews9 (15.52%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other42 (72.41%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (6)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Evaluation of the Effect of Artemisinin-based Combination Therapies on Urinary Schistosoma Haematobium When Administered for the Treatment of Malaria Co-infection[NCT04264130]Phase 254 participants (Actual)Interventional2018-07-31Completed
Parallel Group, Double-blind, Randomized Study Assessing the Efficacy, Safety and Pharmacokinetic Profiles of Ferroquine Associated With Artesunate and a Single-blind Dose Level of Ferroquine Alone in a 3-day Treatment of Uncomplicated Malaria Due to Plas[NCT00988507]Phase 2440 participants (Anticipated)Interventional2009-10-31Terminated(stopped due to Company decision to modify the ferroquine development strategy; discontinuation not due to safety or activity unexpected findings)
An Open Label, 4 Escalating Dose, Randomized Multicentre Study Evaluating the Safety and Activity of Ferroquine Associated With Artesunate Versus a Positive Calibrator (Amodiaquine Associated With Artesunate) in African Adult Patients With Uncomplicated M[NCT00563914]Phase 1/Phase 272 participants (Actual)Interventional2007-10-31Completed
A Randomized, Open Label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 Dose Levels of Artefenomel (OZ439) Given in Combination With Ferroquine (FQ) and FQ Alone, [NCT03660839]Phase 2140 participants (Actual)Interventional2018-09-11Completed
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[NCT02497612]Phase 2377 participants (Actual)Interventional2015-07-25Terminated(stopped due to All treatment arms met the futility criteria for efficacy during the pre-planned interim analysis, therefore the study was stopped.)
Phase Ib, Single-center, Randomized, Study to Determine Safety, Tolerability, and Pharmacokinetics of Different Orally Administered Regimens of the Combination ZY19489-Ferroquine in Adult Asymptomatic Plasmodium Falciparum Carriers[NCT05911828]Phase 136 participants (Anticipated)Interventional2023-07-01Not yet recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT02497612 (25) [back to overview]Parasite Clearance Time: African >5 Years PP Population
NCT02497612 (25) [back to overview]Parasite Clearance Time: Asian PP Population
NCT02497612 (25) [back to overview]Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28: African <=5 Years PP28 Population
NCT02497612 (25) [back to overview]Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP63 Population
NCT02497612 (25) [back to overview]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)
NCT02497612 (25) [back to overview]Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP42 Population
NCT02497612 (25) [back to overview]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)
NCT02497612 (25) [back to overview]Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: Asian PP Population at Day 28 (APP28)
NCT02497612 (25) [back to overview]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)
NCT02497612 (25) [back to overview]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)
NCT02497612 (25) [back to overview]Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Artefenomel
NCT02497612 (25) [back to overview]Pharmacokinetics: Area Under the Curve From Time 0 to Day 28 (AUC0-day28) of Ferroquine
NCT02497612 (25) [back to overview]Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Artefenomel
NCT02497612 (25) [back to overview]Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine (Cmax)
NCT02497612 (25) [back to overview]Time to Re-emergence
NCT02497612 (25) [back to overview]Time to Recrudescence
NCT02497612 (25) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)
NCT02497612 (25) [back to overview]Parasite Reduction Ratio (PRRlog10) at 24 Hours and 48 Hours: African <=5 Years PP Population
NCT02497612 (25) [back to overview]Fever Clearance Time: Asian PP Population
NCT02497612 (25) [back to overview]Parasite Reduction Ratio at 24 Hours and 48 Hours: African >5 Years PP Population
NCT02497612 (25) [back to overview]Parasite Reduction Ratio at 24 Hours and 48 Hours: Asian PP Population
NCT02497612 (25) [back to overview]Fever Clearance Time (FCT): African <=5 Years PP Population
NCT02497612 (25) [back to overview]Fever Clearance Time: African >5 Years PP Population
NCT02497612 (25) [back to overview]Time to Re-infection
NCT02497612 (25) [back to overview]Parasite Clearance Time (PCT): African <=5 Years PP Population
NCT03660839 (21) [back to overview]Parasite Clearance Rate
NCT03660839 (21) [back to overview]Parasite Clearance Time (PCT)
NCT03660839 (21) [back to overview]Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28
NCT03660839 (21) [back to overview]Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 28 (ACPR28)
NCT03660839 (21) [back to overview]Pharmacokinetics: Area Under the Concentration Curve (AUC) Form Time 0 to Infinity (AUC0-inf]) of Artefenomel
NCT03660839 (21) [back to overview]Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose (C168h) of Artefenomel
NCT03660839 (21) [back to overview]Time Elapsed Below the Limit of Quantification (LOQ) of Parasitemia
NCT03660839 (21) [back to overview]Time to Re-emergence
NCT03660839 (21) [back to overview]Time to Re-infection
NCT03660839 (21) [back to overview]Time to Recrudescence
NCT03660839 (21) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)
NCT03660839 (21) [back to overview]Observed Parasite Reduction Ratio (PRR) at 24 Hours, 48 Hours, and 72 Hours
NCT03660839 (21) [back to overview]Parasitemia: Change From Baseline in Number of Parasites Per Microliter of Blood at 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 Hours
NCT03660839 (21) [back to overview]Pharmacokinetics (PK): Concentration of OZ439 in Plasma
NCT03660839 (21) [back to overview]Pharmacokinetics: Area Under the Concentration Curve Form Time 0 to Day 28 (AUC0-28) of Ferroquine and Its Active Metabolite SSR97213
NCT03660839 (21) [back to overview]Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity of Ferroquine and Its Active Metabolite SSR97213
NCT03660839 (21) [back to overview]Pharmacokinetics: Concentration of FQ and Its Active Metabolite SSR97213 in Blood
NCT03660839 (21) [back to overview]Pharmacokinetics: Plasma Concentration at 168 Hours Post-dose of Ferroquine and Its Active Metabolite SSR97213
NCT03660839 (21) [back to overview]Time to 50% and 99% Parasite Reduction
NCT03660839 (21) [back to overview]Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel
NCT03660839 (21) [back to overview]Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine and Its Active Metabolite SSR97213

Parasite Clearance Time: African >5 Years PP Population

"PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). 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." (NCT02497612)
Timeframe: From the start of study drug administration up to the time of the first negative film (up to Day 63)

Interventionhours (Median)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)24.0
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)24.3
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)24.3
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)27.2

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Parasite Clearance Time: Asian PP Population

"PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). 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." (NCT02497612)
Timeframe: From the start of study drug administration up to the time of the first negative film (up to Day 63)

Interventionhours (Median)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)82.0
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)75.1
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)79.8
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)72.2

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

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. (NCT02497612)
Timeframe: Day 28

Interventionpercentage of participants (Number)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)49.3
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)71.6
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)76.2
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)87.1

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

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. (NCT02497612)
Timeframe: Day 63

Interventionpercentage of participants (Number)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)35.3
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)46.2
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)57.6
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)58.3

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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)

"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." (NCT02497612)
Timeframe: Day 28

Interventionpercentage of participants (Number)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)78.4
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)85.0
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)89.5
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)91.7

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

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. (NCT02497612)
Timeframe: Day 42

Interventionpercentage of participants (Number)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)39.1
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)50.8
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)61.0
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)68.9

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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)

"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." (NCT02497612)
Timeframe: Day 28

Interventionpercentage of participants (Number)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)72.7
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)100
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)100
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)90.0

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

"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." (NCT02497612)
Timeframe: Day 28

Interventionpercentage of participants (Number)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)25.0
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)25.0
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)40.0
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)20.0

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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)

"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." (NCT02497612)
Timeframe: Day 42

Interventionpercentage of participants (Number)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)69.8
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)81.8
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)84.0
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)87.7

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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)

"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." (NCT02497612)
Timeframe: Day 63

Interventionpercentage of participants (Number)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)64.1
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)76.7
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)81.8
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)87.2

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Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Artefenomel

Cmax is the maximum observed plasma concentration of artefenomel. (NCT02497612)
Timeframe: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Interventionnanograms per milliliter (Geometric Mean)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)1072
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)936.7
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)771.8
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)797.8

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Pharmacokinetics: Area Under the Curve From Time 0 to Day 28 (AUC0-day28) of Ferroquine

Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours). (NCT02497612)
Timeframe: 2, 4, 6, 8, 12, 24, 48, 168, 336 and 672 hours postdose

Interventionmicrograms*hour per milliliter (Geometric Mean)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)14.92
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)22.56
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)33.84
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)46.4

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Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Artefenomel

Area under the plasma concentration versus time curve from time zero to infinity. (NCT02497612)
Timeframe: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Interventionmicrograms*hour per milliliter (Geometric Mean)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)14.24
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)12.41
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)9.621
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)9.605

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Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine (Cmax)

Cmax is the maximum observed plasma concentration of Ferroquine. (NCT02497612)
Timeframe: 2, 4, 6, 12, 24, 48, 72 and 672 hours post dose

Interventionnanograms per milliliter (Geometric Mean)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)148.1
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)222.8
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)350
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)467.6

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Time to Re-emergence

"Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. 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." (NCT02497612)
Timeframe: Up to Day 63

Interventiondays (Median)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)36.0
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)61.0
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)NA
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)64.0

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Time to Recrudescence

Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Kaplan-Maier method was used for estimation. (NCT02497612)
Timeframe: Up to Day 63

Interventiondays (Median)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)NA
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)NA
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)NA
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)NA

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

An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of 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. (NCT02497612)
Timeframe: From Baseline up to Day 63

,,,
InterventionParticipants (Count of Participants)
Any TEAEAny treatment-emergent SAEAny treatment-emergent AESIAny TEAE led to treatment discontinuationAny TEAE led to death
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)8121120
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)840530
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)872820
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)854930

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Parasite Reduction Ratio (PRRlog10) at 24 Hours and 48 Hours: African <=5 Years PP Population

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. (NCT02497612)
Timeframe: 24 and 48 hours post dose

,,,
Interventionratio (Median)
PRR24 (log10)PRR48 (log10)
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)2.5875.174
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)2.8675.734
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)3.0116.023
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)2.3974.794

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Fever Clearance Time: Asian PP Population

"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." (NCT02497612)
Timeframe: From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)

Interventionhours (Median)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)18.0
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)36.0

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Parasite Reduction Ratio at 24 Hours and 48 Hours: African >5 Years PP Population

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. (NCT02497612)
Timeframe: 24 and 48 hours post dose

,,,
Interventionratio (Median)
PRR24 (log10)PRR48 (log10)
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)3.0546.108
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)2.9795.957
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)4.0698.137
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)3.2886.577

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Parasite Reduction Ratio at 24 Hours and 48 Hours: Asian PP Population

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. (NCT02497612)
Timeframe: 24 and 48 hours post dose

,,,
Interventionratio (Median)
PRR24 (log10)PRR48 (log10)
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)1.3532.705
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)1.1672.335
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)1.1252.250
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)1.6883.377

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Fever Clearance Time (FCT): African <=5 Years PP Population

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. (NCT02497612)
Timeframe: From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)

Interventionhours (Median)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)1.0
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)1.0
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)1.0
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)1.0

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Fever Clearance Time: African >5 Years PP Population

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. (NCT02497612)
Timeframe: From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)

Interventionhours (Median)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)1.0
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)1.0
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)1.5
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)2.0

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Time to Re-infection

Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differs from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Kaplan-Maier method was used for estimation. (NCT02497612)
Timeframe: Up to Day 63

Interventiondays (Median)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)NA
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)NA
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)NA
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)65.0

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Parasite Clearance Time (PCT): African <=5 Years PP Population

"PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). 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." (NCT02497612)
Timeframe: From the start of study drug administration up to the time of the first negative film (up to Day 63)

Interventionhours (Median)
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)36.0
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)36.0
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)36.1
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)36.1

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Parasite Clearance Rate

Parasite clearance rate (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite Clearance Estimator. (NCT03660839)
Timeframe: Up to Day 28

Intervention1 per hour (Mean)
Ferroquine 400 mg0.1956
Ferroquine 400 mg + Artefenomel 300 mg0.3609
Ferroquine 400 mg + Artefenomel 600 mg0.3962
Ferroquine 400 mg + Artefenomel 1000 mg0.3581

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Parasite Clearance Time (PCT)

PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites by microscopy). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. If the second film was performed <6 hours or >12 hours of the first film, then the parasite clearance was confirmed or invalidated by the third (thick) film following the second one, whatever the timing of this third film: If the third film was negative, then the clearance was considered confirmed and if the third film was positive, then the clearance was invalidated. Kaplan-Meier method was used for the estimation. (NCT03660839)
Timeframe: From the start of study drug administration up to the time of the first negative blood film (up to Day 28)

Interventionhours (Median)
Ferroquine 400 mg56.1
Ferroquine 400 mg + Artefenomel 300 mg30.0
Ferroquine 400 mg + Artefenomel 600 mg30.0
Ferroquine 400 mg + Artefenomel 1000 mg30.0

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

ACPR: absence of parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS/SoC/SM at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia; or parasitemia on Day 2 > Day 0 irrespective of AT; or parasitemia on Day 3 with AT >=37.5°C; or parasitemia count on Day 3 >=25% on Day 0, or LCF: DS/SM in presence of parasitemia between Day 4 and 28, concomitant to at least one positive parasitemia; or presence of parasitemia and AT>=37.5°C on Day 4 to Day 28, or LPF: presence of parasitemia between Day 7 and 28 and AT<37.5°C or having rescue therapy for malaria. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish reinfection (new clone of parasite) or recrudescence. (NCT03660839)
Timeframe: Day 28

Interventionpercentage of participants (Number)
Ferroquine 400 mg64.5
Ferroquine 400 mg + Artefenomel 300 mg81.8
Ferroquine 400 mg + Artefenomel 600 mg77.8
Ferroquine 400 mg + Artefenomel 1000 mg78.1

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

ACPR:absence of parasitemia at Day 28, irrespective of axillary temperature(AT), participants not meeting any criteria of early therapy failure(ETF):Danger signs(DS)/symptoms of complicated(SoC)/severe malaria(SM) at Day 1, 2 or 3 in presence of parasitemia, concomitant to at least 1 positive parasitemia;or parasitemia on Day 2 >Day 0 irrespective of AT;or parasitemia on Day 3 with AT>=37.5 degree Celsius (°C);or parasitemia count on Day 3 >=25 percent (%) on Day 0, or late clinical failure (LCF):DS/SM in presence of parasitemia between Day 4 and 28,concomitant to at least one positive parasitemia;or presence of parasitemia and AT>=37.5°C on Day 4 to Day 28, or late parasitological failure(LPF):presence of parasitemia between Day 7 and 28 and AT<37.5°C and without rescue therapy. PCR-corrected ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with reinfection. (NCT03660839)
Timeframe: Day 28

Interventionpercentage of participants (Number)
Ferroquine 400 mg80.8
Ferroquine 400 mg + Artefenomel 300 mg90.3
Ferroquine 400 mg + Artefenomel 600 mg90.9
Ferroquine 400 mg + Artefenomel 1000 mg87.1

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

"Area under the plasma concentration versus time curve from time 0 to infinity. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered." (NCT03660839)
Timeframe: Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose

Interventionmicrograms*hour per milliliter (Geometric Mean)
Ferroquine 400 mg + Artefenomel 300 mg3.269
Ferroquine 400 mg + Artefenomel 600 mg6.46
Ferroquine 400 mg + Artefenomel 1000 mg13.05

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

"The observed plasma concentration of artefenomel post 168 hours of drug administration. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered." (NCT03660839)
Timeframe: At 168 hours post-dose

Interventionnanograms per milliliter (Geometric Mean)
Ferroquine 400 mg + Artefenomel 300 mg0.9251
Ferroquine 400 mg + Artefenomel 600 mg2.152
Ferroquine 400 mg + Artefenomel 1000 mg4.445

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

The time elapsed below LOQ (LOQ expressed in parasites/microliter) of parasitemia (quantitative content of parasites present in the blood) was defined as the time (in days) for which no parasites were seen i.e., time corresponding to PCT, up to the time of occurrence of a new malaria infection or recrudescence. If there was no occurrence of a new malaria infection or recrudescence, then this was the time corresponding to the first negative thick blood film, until the end of study. PCT (k) is the minus slope of the natural logarithm parasitemia versus time linear relationship, after exclusion of outliers, lag phase and Tail, using the worldwide antimalarial resistance network, Parasite clearance estimator. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Meier method was used for estimation. (NCT03660839)
Timeframe: Up to Day 28

Interventiondays (Median)
Ferroquine 400 mg25.0
Ferroquine 400 mg + Artefenomel 300 mg26.0
Ferroquine 400 mg + Artefenomel 600 mg26.5
Ferroquine 400 mg + Artefenomel 1000 mg26.0

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Time to Re-emergence

Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Re-emergence was confirmed by microscopy (positive blood smear). Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation. (NCT03660839)
Timeframe: Up to Day 28

Interventiondays (Median)
Ferroquine 400 mgNA
Ferroquine 400 mg + Artefenomel 300 mgNA
Ferroquine 400 mg + Artefenomel 600 mgNA
Ferroquine 400 mg + Artefenomel 1000 mgNA

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Time to Re-infection

Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differed from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Participants with confirmed parasite clearance were involved in the analysis and Kaplan-Maier method was used for estimation. (NCT03660839)
Timeframe: Up to Day 28

Interventiondays (Median)
Ferroquine 400 mgNA
Ferroquine 400 mg + Artefenomel 300 mgNA
Ferroquine 400 mg + Artefenomel 600 mgNA
Ferroquine 400 mg + Artefenomel 1000 mgNA

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Time to Recrudescence

Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Participants with confirmed parasite clearance were included in the analysis and Kaplan-Meier method was used for estimation. (NCT03660839)
Timeframe: Up to Day 28

Interventiondays (Median)
Ferroquine 400 mgNA
Ferroquine 400 mg + Artefenomel 300 mgNA
Ferroquine 400 mg + Artefenomel 600 mgNA
Ferroquine 400 mg + Artefenomel 1000 mgNA

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

An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to the Day 28. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. (NCT03660839)
Timeframe: From Baseline up to Day 28

,,,
InterventionParticipants (Count of Participants)
Any TEAEAny treatment-emergent SAEAny treatment-emergent AESIAny TEAE led to treatment discontinuationAny TEAE led to death
Ferroquine 400 mg180000
Ferroquine 400 mg + Artefenomel 1000 mg240100
Ferroquine 400 mg + Artefenomel 300 mg210100
Ferroquine 400 mg + Artefenomel 600 mg241000

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

The observed PRR was defined as the ratio of the number of parasites at time t=0 (baseline) divided by the parasite count at each specified time t (post-treatment). If the post dose parasite count = 0 (due to a negative parasitemia) then a value of 1 parasite per microliter was imputed to allow a parasite reduction ratio calculation. (NCT03660839)
Timeframe: Baseline, 24, 48 and 72 hours post-dose

,,,
Interventionratio (Mean)
At Hour 24At Hour 48At Hour 72
Ferroquine 400 mg638.4369709.09315655.447
Ferroquine 400 mg + Artefenomel 1000 mg7929.72019328.05719125.715
Ferroquine 400 mg + Artefenomel 300 mg5921.19717594.70018069.583
Ferroquine 400 mg + Artefenomel 600 mg5715.04613120.40914561.409

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

Parasitemia (quantitative content of parasites present in the blood) at baseline until Day 7 (i.e. 168 hours) was assessed by optical microscope. (NCT03660839)
Timeframe: Baseline, 6, 12, 18, 24, 30, 36, 48, 72, 96, 120, 144 and 168 hours post-dose

,,,
Interventionparasites per microliter (Mean)
BaselineChange from baseline at 6 hours post-doseChange from baseline at 12 hours post-doseChange from baseline at 18 hours post-doseChange from baseline at 24 hours post-doseChange from baseline at 30 hours post-doseChange from baseline at 36 hours post-doseChange from baseline at 48 hours post-doseChange from baseline at 72 hours post-doseChange from baseline at 96 hours post-doseChange from baseline at 120 hours post-doseChange from baseline at 144 hours post-doseChange from baseline at 168 hours post-dose
Ferroquine 400 mg17496.0-1349.3-5721.5-9181.2-14238.4-16571.1-17036.9-17595.3-18231.8-18287.6-19280.0-18526.0-18962.8
Ferroquine 400 mg + Artefenomel 1000 mg20546.8893.2-11319.4-18281.9-19461.9-19657.5-19587.9-20327.7-20314.2-20662.0-20350.4-20029.7-20349.5
Ferroquine 400 mg + Artefenomel 300 mg18799.6-96.9-11471.6-17021.4-17939.0-19110.5-18792.2-17706.1-18396.3-19024.7-19024.7-19023.3-18922.2
Ferroquine 400 mg + Artefenomel 600 mg15171.98515.4-4156.6-9447.5-10674.6-13299.6-14573.9-14542.3-15333.7-15258.5-15265.3-15254.5-15268.5

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Pharmacokinetics (PK): Concentration of OZ439 in Plasma

"Concentrations of OZ439 in plasma was analyzed by liquid chromatography tandem mass spectroscopy (LC-MS/MS). The lower limit of quantification (LLOQ) was 1 nanograms per milliliter for analysis of OZ439. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered." (NCT03660839)
Timeframe: 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose

,,
Interventionnanograms per milliliter (Geometric Mean)
1 hour post-dose2 hours post-dose4 hours post-dose6 hours post-dose12 hours post-dose24 hours post-dose48 hours post-dose72 hours post-dose120 hours post-dose168 hours post-dose336 hours post-dose
Ferroquine 400 mg + Artefenomel 1000 mg188.423655.851978.649865.581369.33584.16729.55416.6658.5965.9033.149
Ferroquine 400 mg + Artefenomel 300 mg88.641269.075349.134234.37592.61417.5266.0973.2242.1441.7451.227
Ferroquine 400 mg + Artefenomel 600 mg149.199450.218576.673478.929164.02848.25714.6118.1625.3393.4081.970

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

Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours). (NCT03660839)
Timeframe: Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

,,,
Interventionmicrograms*hour per milliliter (Geometric Mean)
FQSSR97213
Ferroquine 400 mg8.8748.878
Ferroquine 400 mg + Artefenomel 1000 mg10.148.487
Ferroquine 400 mg + Artefenomel 300 mg10.339.051
Ferroquine 400 mg + Artefenomel 600 mg10.138.483

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

Area under the plasma concentration versus time curve from time 0 to infinity. (NCT03660839)
Timeframe: Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

,,,
Interventionmicrograms*hour per milliliter (Geometric Mean)
FQSSR97213
Ferroquine 400 mg15.519.58
Ferroquine 400 mg + Artefenomel 1000 mg16.8718.32
Ferroquine 400 mg + Artefenomel 300 mg17.8120.09
Ferroquine 400 mg + Artefenomel 600 mg16.317.94

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

Concentrations of FQ and SSR97213 in blood was analyzed by LC-MS/MS. The LLOQ was 5 nanograms per milliliter for analysis of FQ and SSR97213. (NCT03660839)
Timeframe: 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

,,,
Interventionnanograms per milliliter (Geometric Mean)
1 hour post-dose: FQ1 hour post-dose: SSR972134 hours post-dose: FQ4 hours post-dose: SSR972136 hours post-dose: FQ6 hours post-dose: SSR972138 hours post-dose: FQ8 hours post-dose: SSR9721312 hours post-dose: FQ12 hours post-dose: SSR9721324 hours post-dose: FQ24 hours post-dose: SSR9721372 hours post-dose: FQ72 hours post-dose: SSR97213168 hours post-dose: FQ168 hours post-dose: SSR97213336 hours post-dose: FQ336 hours post-dose: SSR97213672 hours post-dose: FQ672 hours post-dose: SSR97213
Ferroquine 400 mg36.09413.20964.93420.07969.00523.17064.29325.13150.62119.95744.35118.87425.34316.75716.97316.30810.54313.6126.7379.751
Ferroquine 400 mg + Artefenomel 1000 mg26.5996.80597.00717.55995.06220.68782.99020.29971.74318.20351.25016.76329.79217.75621.32219.10811.26313.6867.34212.014
Ferroquine 400 mg + Artefenomel 300 mg27.21410.375100.56929.63292.65728.09882.63929.31968.38424.38553.21122.96731.16120.05920.52419.19611.67814.7977.62310.324
Ferroquine 400 mg + Artefenomel 600 mg21.1656.16179.65618.37784.80325.95478.19625.30459.10620.61547.56819.82631.37321.31521.54320.46312.46915.6477.60110.977

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

The observed plasma concentration of FQ and SSR97213 post 168 hours of FQ administration. (NCT03660839)
Timeframe: At 168 hours post-dose

,,,
Interventionnanograms per milliliter (Geometric Mean)
FQSSR97213
Ferroquine 400 mg15.8616.15
Ferroquine 400 mg + Artefenomel 1000 mg17.8314.95
Ferroquine 400 mg + Artefenomel 300 mg18.3216.03
Ferroquine 400 mg + Artefenomel 600 mg18.6915.2

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Time to 50% and 99% Parasite Reduction

Time to 50% and 99% parasite reduction was defined as time needed for the parasitemia (quantitative content of parasites present in blood) to be reduced to 50% and 99% of the initial value, respectively. (NCT03660839)
Timeframe: Up to Day 28

,,,
Interventionhours (Mean)
Time to 50% Parasite reductionTime to 99% Parasite reduction
Ferroquine 400 mg14.0736.92
Ferroquine 400 mg + Artefenomel 1000 mg9.4722.95
Ferroquine 400 mg + Artefenomel 300 mg7.7419.33
Ferroquine 400 mg + Artefenomel 600 mg7.7818.34

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Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Artefenomel

"Cmax is the maximum observed plasma concentration of Artefenomel. Data for this outcome measure was not planned to be collected and analyzed for Ferroquine 400 mg arm, since artefenomel was not administered." (NCT03660839)
Timeframe: Pre-dose, 1, 2, 4, 6, 12, 24, 48, 72, 120, 168 and 336 hours post-dose

Interventionnanograms per milliliter (Geometric Mean)
Ferroquine 400 mg + Artefenomel 300 mg277.3
Ferroquine 400 mg + Artefenomel 600 mg488.3
Ferroquine 400 mg + Artefenomel 1000 mg920.6

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

Cmax is the maximum observed plasma concentration of Ferroquine. (NCT03660839)
Timeframe: Pre-dose, 1, 4, 6, 8, 12, 24, 72, 168, 336 and 672 hours post-dose

,,,
Interventionnanograms per milliliter (Geometric Mean)
FQSSR97213
Ferroquine 400 mg80.9924.58
Ferroquine 400 mg + Artefenomel 1000 mg82.4519.76
Ferroquine 400 mg + Artefenomel 300 mg79.9522.65
Ferroquine 400 mg + Artefenomel 600 mg72.6419.14

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SubstanceRelationship StrengthStudiesTrialsClassesRoles
aminolevulinic acid
Aminolevulinic Acid: A compound produced from succinyl-CoA and GLYCINE as an intermediate in heme synthesis. It is used as a PHOTOCHEMOTHERAPY for actinic KERATOSIS.. 5-aminolevulinic acid : The simplest delta-amino acid in which the hydrogens at the gamma position are replaced by an oxo group. It is metabolised to protoporphyrin IX, a photoactive compound which accumulates in the skin. Used (in the form of the hydrochloride salt)in combination with blue light illumination for the treatment of minimally to moderately thick actinic keratosis of the face or scalp.		2.08104-oxo monocarboxylic acid;
amino acid zwitterion;
delta-amino acid		antineoplastic agent;
dermatologic drug;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
photosensitizing agent;
plant metabolite;
prodrug;
Saccharomyces cerevisiae metabolite
amodiaquine
Amodiaquine: A 4-aminoquinoline compound with anti-inflammatory properties.. amodiaquine : A quinoline having a chloro group at the 7-position and an aryl amino group at the 4-position.		11.1532aminoquinoline;
organochlorine compound;
phenols;
secondary amino compound;
tertiary amino compound		anticoronaviral agent;
antimalarial;
drug allergen;
EC 2.1.1.8 (histamine N-methyltransferase) inhibitor;
non-steroidal anti-inflammatory drug;
prodrug
chloroquine
Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.. chloroquine : An aminoquinoline that is quinoline which is substituted at position 4 by a [5-(diethylamino)pentan-2-yl]amino group at at position 7 by chlorine. It is used for the treatment of malaria, hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis.		6.45170aminoquinoline;
organochlorine compound;
secondary amino compound;
tertiary amino compound		anticoronaviral agent;
antimalarial;
antirheumatic drug;
autophagy inhibitor;
dermatologic drug
ciprofloxacin
Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.. ciprofloxacin : A quinolone that is quinolin-4(1H)-one bearing cyclopropyl, carboxylic acid, fluoro and piperazin-1-yl substituents at positions 1, 3, 6 and 7, respectively.		2.0510aminoquinoline;
cyclopropanes;
fluoroquinolone antibiotic;
N-arylpiperazine;
quinolinemonocarboxylic acid;
quinolone antibiotic;
quinolone;
zwitterion		antibacterial drug;
antiinfective agent;
antimicrobial agent;
DNA synthesis inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
environmental contaminant;
topoisomerase IV inhibitor;
xenobiotic
clofazimine
Clofazimine: A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. (From AMA Drug Evaluations Annual, 1993, p1619). clofazimine : 3-Isopropylimino-3,5-dihydro-phenazine in which the hydrogen at position 5 is substituted substituted by a 4-chlorophenyl group, and that at position 2 is substituted by a (4-chlorophenyl)amino group. A dark red crystalline solid, clofazimine is an antimycobacterial and is one of the main drugs used for the treatment of multi-bacillary leprosy. However, it can cause red/brown discolouration of the skin, so other treatments are often preferred in light-skinned patients.		2.2510monochlorobenzenes;
phenazines		dye;
leprostatic drug;
non-steroidal anti-inflammatory drug
deferoxamine
Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.. desferrioxamine B : An acyclic desferrioxamine that is butanedioic acid in which one of the carboxy groups undergoes formal condensation with the primary amino group of N-(5-aminopentyl)-N-hydroxyacetamide and the second carboxy group undergoes formal condensation with the hydroxyamino group of N(1)-(5-aminopentyl)-N(1)-hydroxy-N(4)-[5-(hydroxyamino)pentyl]butanediamide. It is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator.		2.0810acyclic desferrioxaminebacterial metabolite;
ferroptosis inhibitor;
iron chelator;
siderophore
primaquine
Primaquine: An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. (From Martindale, The Extra Pharmacopeia, 30th ed, p404). primaquine : An N-substituted diamine that is pentane-1,4-diamine substituted by a 6-methoxyquinolin-8-yl group at the N(4) position. It is a drug used in the treatment of malaria and Pneumocystis pneumonia.		2.2510aminoquinoline;
aromatic ether;
N-substituted diamine		antimalarial
protoporphyrin ix
protoporphyrin IX: RN given refers to parent cpd; structure in Merck Index, 9th ed, #7685. protoporphyrin : A cyclic tetrapyrrole that consists of porphyrin bearing four methyl substituents at positions 3, 8, 13 and 17, two vinyl substituents at positions 7 and 12 and two 2-carboxyethyl substituents at positions 2 and 18. The parent of the class of protoporphyrins.		2.0810
carbostyril
Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.. quinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2.		2.1110monohydroxyquinoline;
quinolone		bacterial xenobiotic metabolite
quinoline
[no description available]		7.0410azaarene;
mancude organic heterobicyclic parent;
ortho-fused heteroarene;
quinolines
acridines
Acridines: Compounds that include the structure of acridine.. acridine : A polycyclic heteroarene that is anthracene in which one of the central CH groups is replaced by a nitrogen atom.		3.2310acridines;
mancude organic heterotricyclic parent;
polycyclic heteroarene		genotoxin
adamantane
Adamantane: A tricyclo bridged hydrocarbon.		5.4741adamantanes;
polycyclic alkane
alpha-aminopyridine
alpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485. aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups.		2.2510
lucanthone hydrochloride
Schistosomicides: Agents that act systemically to kill adult schistosomes.		2.110
iridium
Iridium: A metallic element with the atomic symbol Ir, atomic number 77, and atomic weight 192.22.		3.3510cobalt group element atom;
platinum group metal atom
osmium
Osmium: A very hard, gray, toxic, and nearly infusible metal element, atomic number 76, atomic weight 190.2, symbol Os.		3.3510iron group element atom;
platinum group metal atom
palladium
Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys.. palladium : Chemical element (nickel group element atom) with atomic number 46.		3.3510metal allergen;
nickel group element atom;
platinum group metal atom
platinum
Platinum: A heavy, soft, whitish metal, resembling tin, with atomic number 78, atomic weight 195.084, symbol Pt. It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as alutiae.		3.3510elemental platinum;
nickel group element atom;
platinum group metal atom
rhenium
Rhenium: A metal, atomic number 75, atomic weight 186.207, symbol Re.		2.0510manganese group element atom
rhodium
Rhodium: A hard and rare metal of the platinum group, atomic number 45, atomic weight 102.905, symbol Rh.. rhodium atom : A cobalt group element atom of atomic number 45.		3.3510cobalt group element atom
ruthenium
Ruthenium: A hard, brittle, grayish-white rare earth metal with an atomic symbol Ru, atomic number 44, and atomic weight 101.07. It is used as a catalyst and hardener for PLATINUM and PALLADIUM.		3.8930iron group element atom;
platinum group metal atom
halofantrine
halofantrine: used in treatment of mild to moderate acute malaria		2.2510phenanthrenes
triazoles
Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.		2.25101,2,3-triazole
4-aminoquinoline
[no description available]		8.8730
artemisinin
(+)-artemisinin : A sesquiterpene lactone obtained from sweet wormwood, Artemisia annua, which is used as an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria.		3.2710organic peroxide;
sesquiterpene lactone		antimalarial;
plant metabolite
artemether
Artemether: An artemisinin derivative that is used in the treatment of MALARIA.. artemether : An artemisinin derivative that is artemisinin in which the lactone has been converted to the corresponding lactol methyl ether. It is used in combination with lumefantrine as an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria.		4.7211artemisinin derivative;
cyclic acetal;
organic peroxide;
semisynthetic derivative;
sesquiterpenoid		antimalarial
artesunic acid
[no description available]		7.0343
tafenoquine
tafenoquine : A racemate comprising equimolar amounts of (R)- and (S)-tafenoquine.. N(4)-{2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl}pentane-1,4-diamine : An aminoquinoline that is 8-aminoquinoline which is substituted by methoxy groups at positions 2 and 6, a methyl group at position 4, and a m-(trifluoromethyl)phenoxy group at position 5, and in which the amino substituent at position 8 is itself substituted by a 5-aminopentan-2-yl group.		3.2710(trifluoromethyl)benzenes;
aminoquinoline;
aromatic ether;
primary amino compound;
secondary amino compound
desethylamodiaquine
desethylamodiaquine: metabolite of amodiaquine		2.0410
piperaquine
piperaquine : An aminoquinoline that is 1,3-di(piperazin-1-yl)propane in which the nitrogen at position 4 of each of the piperazine moieties is replaced by a 7-chloroquinolin-4-yl group.		2.2510aminoquinoline;
N-arylpiperazine;
organochlorine compound		antimalarial
proline
Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.. proline : An alpha-amino acid that is pyrrolidine bearing a carboxy substituent at position 2.		2.0810amino acid zwitterion;
glutamine family amino acid;
L-alpha-amino acid;
proline;
proteinogenic amino acid		algal metabolite;
compatible osmolytes;
Escherichia coli metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
hydroxyl radical
Hydroxyl Radical: The univalent radical OH. Hydroxyl radical is a potent oxidizing agent.		2.4820oxygen hydride;
oxygen radical;
reactive oxygen species
aminoquinolone
aminoquinolone: metabolite of peptido-aminobenzophenone; structure given in first source		3.2310
sesquiterpenes
[no description available]		2.0210
tamoxifen
[no description available]		3.3510stilbenoid;
tertiary amino compound		angiogenesis inhibitor;
antineoplastic agent;
bone density conservation agent;
EC 1.2.3.1 (aldehyde oxidase) inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
estrogen antagonist;
estrogen receptor antagonist;
estrogen receptor modulator
lumefantrine
Lumefantrine: A fluorene derivative that is used in combination with ARTEMETHER for the treatment of MALARIA (see ARTEMETHER-LUMEFANTRINE DRUG COMBINATION).. lumefantrine : A member of the class of fluorenes that is 9-(p-chlorobenzylidene)-9H-fluorene which is substitutec by chlorine at positions 2 and 7, and by a 2-(dibutylamino)-1-hydroxyethyl group at position 4. An antimalarial drug used in combination with artemether for the treatment of multi-drug resistant strains of falciparum malaria.		3.7120fluorenes;
monochlorobenzenes;
secondary alcohol;
tertiary amine		antimalarial
cgp-56697
Artemether, Lumefantrine Drug Combination: Drug combination of artemether and lumefantrine that is used to treat PLASMODIUM FALCIPARUM MALARIA.		4.7211
mefloquine
Mefloquine: A phospholipid-interacting antimalarial drug (ANTIMALARIALS). It is very effective against PLASMODIUM FALCIPARUM with very few side effects.. mefloquine : A racemate composed of (+)-(11R,2'S)- and (-)-(11S,2'R)-enantiomers of mefloquine. An antimalarial agent which acts as a blood schizonticide; its mechanism of action is unknown.		2.4320
oz 439
artefenomel: an antimalarial ozonide; structure in first source		7.2463
nitd 609
NITD 609: an antimalarial and coccidiostat; structure in first source		2.2510
kaf156
ganaplacide: antimalarial		3.2710
salicylates
Salicylates: The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.. hydroxybenzoate : Any benzoate derivative carrying a single carboxylate group and at least one hydroxy substituent.. salicylates : Any salt or ester arising from reaction of the carboxy group of salicylic acid, or any ester resulting from the condensation of the phenolic hydroxy group of salicylic acid with an organic acid.. salicylate : A monohydroxybenzoate that is the conjugate base of salicylic acid.		3.3510monohydroxybenzoateplant metabolite
sj733
SJ733: antimalarial; structure in first source		2.2510
phenanthrenes
Phenanthrenes: POLYCYCLIC AROMATIC HYDROCARBONS composed of three fused BENZENE rings.. phenanthrenes : Any benzenoid aromatic compound that consists of a phenanthrene skeleton and its substituted derivatives thereof.		2.2510
ConditionIndicatedRelationship StrengthStudiesTrials
Infections, Plasmodium
[description not available]		08.78121
Plasmodium falciparum Malaria
[description not available]		010.24177
Schistosoma haematobia Infection
[description not available]		04.7211
Malaria
A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.		08.78121
Schistosomiasis haematobia
A human disease caused by the infection of parasitic worms SCHISTOSOMA HAEMATOBIUM. It is endemic in AFRICA and parts of the MIDDLE EAST. Tissue damages most often occur in the URINARY TRACT, specifically the URINARY BLADDER.		04.7211
Malaria, Falciparum
Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.		010.24177
Autokinetic Effect
[description not available]		03.5210
Benign Neoplasms
[description not available]		03.520
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		03.520
Parasitemia
The presence of parasites (especially malarial parasites) in the blood. (Dorland, 27th ed)		02.4920
Acute Liver Injury, Drug-Induced
[description not available]		02.2510
Chemical and Drug Induced Liver Injury
A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment.		02.2510
Schistosoma mansoni Infection
[description not available]		02.110
Schistosomiasis mansoni
Schistosomiasis caused by Schistosoma mansoni. It is endemic in Africa, the Middle East, South America, and the Caribbean and affects mainly the bowel, spleen, and liver.		02.110
African Sleeping Sickness
[description not available]		02.520
Trypanosomiasis, African
A disease endemic among people and animals in Central Africa. It is caused by various species of trypanosomes, particularly T. gambiense and T. rhodesiense. Its second host is the TSETSE FLY. Involvement of the central nervous system produces African sleeping sickness. Nagana is a rapidly fatal trypanosomiasis of horses and other animals.		02.520
Plasmodium vivax Malaria
[description not available]		03.3820
Malaria, Vivax
Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.		03.3820
Asymptomatic Conditions
[description not available]		03.4511
Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted
[description not available]		02.0810
Hepatitis C
INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.		07.0810
Cancer of Prostate
[description not available]		02.0810
Prostatic Neoplasms
Tumors or cancer of the PROSTATE.		02.0810