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

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).