Journal Article

Efficacy, safety, and palatability of arpraziquantel (L-praziquantel) orodispersible tablets in children aged 3 months to 6 years infected with Schistosoma in Côte d'Ivoire and Kenya: an open-label, partly randomised, phase 3 trial

Odiere, Maurice R, Aka, N A David, Ogutu, Bernhards, Bödding, Matthias, Kourany-Lefoll, Elly, Rawago, Fredrick, Bagchus, Wilhelmina M, Dälken, Benjamin, Assandé Aka, Ronald, Yin, Xiaoyan, Huber, Eric, Ouattara, Mamadou, Bezuidenhout, Deon, Badenhorst, Henk, N'Goran, Eliézer K, Tappert, Aliona, Haj-Ali Saflo, Okba

2023

Overview

WHO has underlined the need for a child-friendly treatment for schistosomiasis, a prevalent parasitic disease in low-income and middle-income countries. After successful phase 1 and 2 trials, we aimed to evaluate the efficacy, safety, palatability, and pharmacokinetics of arpraziquantel (L-praziquantel) orodispersible tablets for preschool-aged children. This open-label, partly randomised, phase 3 study was conducted at two hospitals in Côte d'Ivoire and Kenya. Children with a minimum bodyweight of 5 kg in those aged 3 months to 2 years and 8 kg in those aged 2–6 years were eligible. In cohort 1, participants aged 4–6 years infected with Schistosoma mansoni were randomly assigned (2:1) to receive a single dose of oral arpraziquantel 50 mg/kg (cohort 1a) or oral praziquantel 40 mg/kg (cohort 1b) using a computer-generated randomisation list. Cohorts 2 (aged 2–3 years) and 3 (aged 3 months to 2 years) infected with S mansoni, and the first 30 participants in cohort 4a (aged 3 months to 6 years) infected with Schistosoma haematobium, received a single dose of oral arpraziquantel 50 mg/kg. After follow-up assessments, arpraziquantel was increased to 60 mg/kg (cohort 4b). Laboratory personnel were masked to the treatment group, screening, and baseline values. S mansoni was detected using a point-of-care circulating cathodic antigen urine cassette test and confirmed using the Kato-Katz method. The primary efficacy endpoint was clinical cure rate at 17–21 days after treatment in cohorts 1a and 1b, measured in the modified intention-to-treat population and calculated using the Clopper-Pearson method. This study is registered with ClinicalTrials.gov, NCT03845140. Between Sept 2, 2019, and Aug 7, 2021, 2663 participants were prescreened and 326 were diagnosed with S mansoni or S haematobium. 288 were enrolled (n=100 in cohort 1a, n=50 in cohort 1b, n=30 in cohort 2, n=18 in cohort 3, n=30 in cohort 4a, and n=60 in cohort 4b), but eight participants received antimalarial drugs and were excluded from the efficacy analyses. The median age was 5·1 years (IQR 4·1–6·0) and 132 (47%) of 280 participants were female and 148 (53%) were male. Cure rates with arpraziquantel were similar to those with praziquantel (87·8% [95% CI 79·6–93·5] in cohort 1a vs 81·3% [67·4–91·1] in cohort 1b). No safety concerns were identified during the study. The most common drug-related treatment-emergent adverse events were abdominal pain (41 [14%] of 288 participants), diarrhoea (27 [9%]), vomiting (16 [6%]), and somnolence (21 [7%]). Arpraziquantel, a first-line orodispersible tablet, showed high efficacy and favourable safety in preschool-aged children with schistosomiasis. The Global Health Innovative Technology Fund, the European and Developing Countries Clinical Trials Partnership, and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Animals / Anthelmintics - adverse effects / Antigens / Antimalarial agents / Chemotherapy / Child, Preschool / Children / Children & youth / Clinical trials / Convulsions & seizures / Cote d'Ivoire / Developing countries / Diarrhea / Effectiveness / Ethics / Female / Global health / Health services / Humans / Income / Infections / Infectious diseases / International organizations / Kenya / Laboratories / LDCs / Male / Morbidity / Palatability / Parasitic diseases / Pediatrics / Pharmacokinetics / Praziquantel / Praziquantel - adverse effects / Public health / Randomization / Safety / Schistosoma mansoni / Schistosomiasis / Schistosomiasis - drug therapy / Schistosomiasis mansoni - diagnosis / Schistosomiasis mansoni - drug therapy / Schistosomiasis mansoni - prevention & control / Tablets / Tropical diseases / Viral infections / Vomiting