Efficacy of OZ439 (artefenomel) against early Plasmodium falciparum blood-stage malaria infection in healthy volunteers

McCarthy, James S., Baker, Mark, O'Rourke, Peter, Marquart, Louise, Griffin, Paul, van huijsduijnen, Rob Hooft and Mohrle, Jorg J. (2016) Efficacy of OZ439 (artefenomel) against early Plasmodium falciparum blood-stage malaria infection in healthy volunteers. Journal of Antimicrobial Chemotherapy, 71 9: 2620-2627. doi:10.1093/jac/dkw174


Author McCarthy, James S.
Baker, Mark
O'Rourke, Peter
Marquart, Louise
Griffin, Paul
van huijsduijnen, Rob Hooft
Mohrle, Jorg J.
Title Efficacy of OZ439 (artefenomel) against early Plasmodium falciparum blood-stage malaria infection in healthy volunteers
Formatted title
Efficacy of OZ439 (artefenomel) against early Plasmodium falciparum blood-stage malaria infection in healthy volunteers
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 0305-7453
1460-2091
Publication date 2016-04
Sub-type Article (original research)
DOI 10.1093/jac/dkw174
Open Access Status DOI
Volume 71
Issue 9
Start page 2620
End page 2627
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2017
Language eng
Formatted abstract
Objectives: OZ439, or artefenomel, is an investigational synthetic ozonide antimalarial with similar potency, but a significantly improved pharmacokinetic profile, compared with artemisinins. We wished to measure key pharmacokinetic and pharmacodynamic parameters and the pharmacokinetic/pharmacodynamic relationship of artefenomel in humans to guide the drug’s further development as combination therapy in patients. 

Patients and methods: We tested artefenomel in the human induced blood-stage malaria (IBSM) model. Plasmodium infection was monitored by quantitative PCR (qPCR) and upon reaching 1000 parasites/mL single doses of 100, 200 and 500 mg of artefenomel were administered orally with evaluation of drug exposure and parasitaemia until rescue treatment after 16 days or earlier, if required.

Results:
A single 100 mg dose had only a transient effect, while the 200 mg dose resulted in a significant reduction in parasitaemia before early recrudescence. At the highest (500 mg) dose, initial clearance of parasites below the limit of detection of qPCR was observed, with a 48 h parasite reduction ratio (PRR48) .10000 and a parasite clearance half-life of of 3.6 h (95% CI 3.4–3.8 h). However, at this dose, recrudescence was seen in four of eight subjects 6–10 days after treatment. Pharmacokinetic/pharmacodynamic modelling predicted an MIC of 4.1 ng/mL.

Conclusions: These results confirm the antimalarial potential of artefenomel for use in a single-exposure combination therapy. The observations from this study support and will assist further clinical development of artefenomel.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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Created: Mon, 25 Apr 2016, 11:34:37 EST by Paul Griffin on behalf of Medicine - Mater Hospital