A clinical phase III comparative, randomised, clinical trial to assess the safety and efficacy of a fixed dose of oral pyronaridine-artesunate granule formulation (60:20) (paediatric Pyramax®) versus artemether-lumefantrine (Coartem®) crushed tablets in infants and children with acute uncomplicated Plasmodium falciparum malaria in Lambaréné, Gabon

Abstract

The study assessed the efficacy and safety of a fixed dose of oral pyronaridine-artesunate granule formulation (60:20) (paediatric Pyramax®) compared to artesunate-lumefantrine (Coartem®) crushed tablets in infants and children with acute uncomplicated P. falciparum malaria. The study was part of a multicenter, comparative, randomized, open-labeled, parallel group study on the efficacy, safety and pharmacokinetics of the investigational drug conducted in a total of 534 male and female infants and children (between ≥ 5 kg and < 25 kg body weight) suffering from acute symptomatic uncomplicated P. falciparum malaria recruited from study sites located in Africa and the Philippines. A total of 80 subjects with similar demographic and clinical characteristics at baseline were enrolled in the study. Fifty-three patients received pyronaridine-artesunate granule formulation (60:20 mg) daily for 3 days and 27 received artemether-lumefantrine crushed tablets as drug comparator. The primary outcome was achieved as the cure rate at Day 28 in the pyronaridine-artesunate group (PCR-corrected ACPR in the efficacy-evaluable population) was of 100%. Moreover, non-inferiority of the investigational drug compared to artemether-lumefantrine was demonstrated on Day 28 and on Day 42 in the efficacy-evaluable population. Furthermore, parasite clearance was significantly shorter with pyronaridine-artesunate. Overall adverse events incidence and severity were similar between groups. Neither serious nor adverse events leading to study neither drug discontinuation nor withdrawal occurred in the course of the study. Adverse events considered by investigators as drug related occurred in 11% of the patients receiving pyronaridine-artesunate and were mostly mild gastrointestinal disorders. Pyronaridine-artesunate pediatric granules were efficacious, safe and well tolerated in this study in children under 12 years of age with uncomplicated P. falciparum malaria. Pyronaridine-artesunate granule co-formulation appears to be a valuable ACT for use in children and infants with uncomplicated P. falciparum.