Pharmacokinetics of ganaplacide and lumefantrine in a pediatric population with Plasmodium falciparum uncomplicated malaria, treated with ganaplacide plus lumefantrine solid dispersion formulation: analysis of data from KALUMI, a multinational Phase 2 study
Year: 2026
Type: preprint
Abstract: Background The new antimalarial combination ganaplacide plus lumefantrine-SDF was shown in a previous phase 2 study to be effective and well-tolerated in the treatment of uncomplicated falciparum malaria in adults, adolescents and children ≥ 2 years old. Here we report pharmacokinetic data from a second phase 2 study, which aimed to optimize the dose regimen and food intake with dosing, and to assess efficacy, safety and pharmacokinetics in children aged 6 months to 2 years with acute uncomplicated falciparum malaria. Methods In this randomized, open-label phase 2 study in uncomplicated falciparum malaria, sequential cohorts of patients aged 2 to < 12 years, body weight ≥ 10 kg (Cohort 1, N = 140), and 6 months to < 2 years, body weight ≥ 5 kg (Cohort 2, N = 80) were randomized to a loose combination of ganaplacide 400 mg plus lumefantrine solid dispersion formulation (SDF) 480 mg, administered with a light meal (100–300 calories, 5-10g fat) q.d. for 3 days, or artemether-lumefantrine (b.i.d. 3 days, per prescribing information). Doses were adjusted by body weight range. The ganaplacide plus lumefantrine-SDF treatment regimen was selected based on data from run-in cohorts of patients aged 12 to < 18 years (reported separately). We report pharmacokinetic data from the study. Sparse sampling was used. Drug concentrations were determined by liquid chromatography-mass spectrometry. Pharmacokinetic parameters including AUC 0−24 , C max , and C 168h were determined using non-compartmental analysis. Results Ganaplacide and lumefantrine exposures were within targeted ranges in both cohorts as confirmed by good efficacy and safety. Lumefantrine C 168h was higher in the ganaplacide plus lumefantrine-SDF group than the artemether-lumefantrine group in both cohorts. Drug exposures were comparable to those in patients treated with ganaplacide 400 mg plus lumefantrine-SDF 960 mg (doses adjusted by body weight range) given under fasted conditions in a previous study. Conclusions Ganaplacide 400 mg plus lumefantrine-SDF 480 mg given with a light meal q.d. for 3 days achieved effective drug exposures in patients with uncomplicated falciparum malaria. Trial registration The study is registered with EudraCT (2021-003583-27) and ClinicalTrials.gov (NCT04546633).
Source: Research Square
Authors: Ramachandra Sangana, Bakary Fofana, Rella Zoleko Manego, Sodiomon Bienvenu Sirima, Andre Toure Offianan, Jean Bosco Ouedraogo, Mulenge Kilowele, Anne Claire Marrast, Myriam El-Gaaloul, Celine Risterucci, Guoqin Su, Gen Zhu, Jared Thornton, Hira Choudhury, Jayant Sancheti, Cornelis Winnips, Issaka Sagara, Zhiyan Qian
Institutions: Université des Sciences, des Techniques et des Technologies de Bamako, Institut Pasteur de Côte d'Ivoire, Institut d'Histoire et de Philosophie des Sciences et des Techniques, Medicines for Malaria Venture, Novartis (Switzerland), Novartis (United States), Novartis (United Kingdom), Novartis (India)
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225743568