Pharmacokinetics of Ganaplacide and Lumefantrine in Adults,Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study

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dc.contributor.authorSangana, Ramachandra
dc.contributor.authorOgutu, Bernhards
dc.contributor.authorYeka, Adoke
dc.contributor.authorKusemererwa, Sylvia
dc.contributor.authorWinnips, Cornelis
dc.contributor.authorZhang, Jie
dc.contributor.authorZack, Julia
dc.date.accessioned2025-03-19T08:18:50Z
dc.date.available2025-03-19T08:18:50Z
dc.date.issued2025-03-15
dc.description.abstractThe novel antimalarial ganaplacide combined with lumefantrine solid dispersion formulation (LUM-SDF) was effective and well tolerated in the treatment of uncomplicated falciparum malaria in adults, adolescents, and children in a multinational, prospective, randomized, active-controlled Phase II study conducted between August 2017 and June 2021 (EudraCT 2020-003284-25, Clinicaltrials.gov NCT03167242). Pharmacokinetic data from that study are reported here. The trial comprised three parts: a run-in part in 12 adult/adolescent patients treated with a single dose of ganaplacide 200 mg plus LUM-SDF 960 mg assessed potential pharmacokinetic (PK) interactions between ganaplacide and lumefantrine; in Part A, adult/adolescent patients received one of the six ganaplacide-LUM-SDF regimens or artemether-lumefantrine; and in Part B, three dose regimens identified in Part A, and artemether-lumefantrine, were assessed in children aged 2 to <12 years, with body weight ≥10 kg. A rich blood sampling schedule was used for all 12 patients in the PK run-in part and a subset of patients (N = 32) in Part A, with sparse sampling for remaining patients in Parts A (N = 275) and B (N = 159). Drug concentrations were determined by a validated protein precipitation and reverse phase liquid chromatography with tandem mass spectrometry detection method. Parameters including AUCinf, AUClast, AUC0-t, Cmax, and tmax were reported where possible, using non-compartmental analysis. In the PK run-in part, there was no notable increase in ganaplacide or lumefantrine exposure when co-administered. In Parts A and B, ganaplacide exposures increased with dose, but lumefantrine exposure was numerically under dose-proportional. Lumefantrine exposure was higher with ganaplacide-LUM-SDF than with artemether-lumefantrine, although high variability was observed. Ganaplacide and lumefantrine exposures (Cmax and AUC0-24 h) were comparable across age and body weight groups. Drug exposures needed for efficacy were achieved using the dose regimen 400 mg ganaplacide plus lumefantrine 960 mg once daily for 3 days under fasted conditions.
dc.identifier.citationSangana, R., Ogutu, B., Yeka, A., Kusemererwa, S., Tinto, H., Toure, A. O., ... & Zack, J. (2025). Pharmacokinetics of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study. The Journal of Clinical Pharmacology, 65(2), 179-189.
dc.identifier.otherhttps://doi.org/10.1002/jcph.6138
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/10150
dc.language.isoen
dc.publisherThe Journal of Clinical Pharmacology
dc.titlePharmacokinetics of Ganaplacide and Lumefantrine in Adults,Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study
dc.typeArticle
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