Sangana, Ramachandra, Ogutu, Bernhards, Yeka, Adoke, Kusemererwa, Sylvia, Thompson, Ricardo, Tinto, Halidou, Toure, Andre Offianan, Kibuuka, Afizi, Lingani, Moussa, Lourenço, Carlos, Mombo-Ngoma, Ghyslain, Nduba, Videlis, Guessan, Tiacoh Landry N, Nassa, Guétawendé Job Wilfried, Nyantaro, Mary, Tina, Lucas Otieno, Anvikar, Anup, Sinha, Abhinav, Kaguthi, Grace, Fofana, Bakary, Grobusch, Martin Peter, El Gaaloul, Myriam, Marrast, Anne Claire, Pathan, RashidKhan, Chikoto, Havana, Csermak Renner, Katalin, Risterucci, Celine, Su, Guoqin, Winnips, Cornelis, Zhang, Jie and Zack, Julia (2024) Pharmacokinetics of ganaplacide and lumefantrine: data from a Phase 2 study in adults, adolescents, and children with Plasmodium falciparum malaria in Africa treated with ganaplacide plus lumefantrine solid dispersion formulation. The Journal of Clinical Pharmacology. ISSN 0091-27001552-4604

Abstract

The novel antimalarial ganaplacide combined with lumefantrine solid dispersion formulation (LUM-SDF) was effective and well-tolerated in the treatment of falciparum malaria in adults, adolescents and children in a randomized, active-controlled Phase 2 trial (EudraCT 2020-003284-25, Clinicaltrials.gov NCT03167242). Pharmacokinetic data from that study are reported here.
The trial comprised 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 PK interactions between ganaplacide and lumefantrine; in Part A, 337 adult/adolescent patients received one of 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 175 children aged 2 to <12 years old, body weight ≥10 kg. A rich blood sampling schedule was used for all patients in the PK run-in part and a subset of patients in Part A, with sparse sampling for remaining patients in Parts A and B.
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 on co-administration. In Parts A and B, ganaplacide exposures increased with dose, but lumefantrine exposure was 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 AUC0-24h) were comparable across age and body weight groups.

Item Type:	Article
Keywords:	Plasmodium falciparum malaria, ganaplacide, lumefantrine, pharmacokinetics
Date Deposited:	15 Oct 2024 00:45
Last Modified:	15 Oct 2024 00:45
URI:	https://oak.novartis.com/id/eprint/53942