Identification of a moxidectin dose for 4- to 11-year-old children to support registration and potential use for onchocerciasis elimination: results of an open-label pharmacokinetic and safety study.

backgroundThe WHO and onchocerciasis-endemic countries target elimination of the transmission of Onchocerca volvulus, the parasite causing onchocerciasis, primarily through ivermectin mass drug administration (MDA). In Africa, alternative treatment strategies are required to achieve or accelerate elimination. One of these is the MDA of moxidectin, an anthelmintic drug for which an 8 mg dose to individuals aged 12 years and older has received regulatory approval. This study was conducted to identify dose levels for children aged 4 to 11 years.

methodsAn open-label, non-comparative, single-dose study in an onchocerciasis-endemic area of Ghana was designed to evaluate moxidectin pharmacokinetics and safety in four groups comprising nine individuals each: those aged 12-17 years, after administration of 8 mg; those aged 8-11 years after administration of 8 mg; those aged 8-11 years after administration of 6 mg; and those aged 4-7 years after administration of 4 mg moxidectin. Evaluations to identify adverse events included physical examination, vital signs, haematology, clinical chemistry and 12-lead electrocardiograms. Moxidectin plasma concentrations were measured at 1, 2, 4, 8, 24 and 72 h and at 1, 2, 4 and 12 weeks post-dose. The maximum concentration (C

resultsThe 38 adverse events in 24 participants were illnesses typically seen in the study population without treatment (primarily malaria) and were considered not moxidectin-related. The arithmetic mean (± standard deviation) C

conclusionsConsidering the safety data, exposures and potential MDA operational aspects, 8 mg for children aged between 8 and 11 years and 4 mg for children aged between 4 and 7 years were selected for further single-dose studies.