Open-label trial of three dosage regimens of fixed-dose combination of artemisinin and naphthoquine for treating uncomplicated falciparum malaria in calabar, Nigeria

BACKGROUND: The use of anti-malarial drug combinations with artemisinin, or with one of its derivatives, is now widely recommended to overcome drug resistance in falciparum malaria. Fixed-dose combination of artemisinin and naphthoquine is a new generation artemisinin combination therapy (ACT) offered as a single dose therapy. The aim of the study was to assess the therapeutic efficacy, safety and tolerability of three dosage schedules of fixed-dose combination of artemisinin (125 mg) and naphthoquine (50 mg) for treating uncomplicated Plasmodium falciparum malaria among adolescents and adults in Calabar, South-east Nigeria. METHOD: A total of 121 patients aged ≥15 years with uncomplicated P. falciparum malaria were enrolled and randomly assigned to three dosage schedules: (A) 700 mg (four tablets) single dose; (B) 700 mg 12-hourly x two doses; and (C) 1,400 mg (eight tablets) single dose. Patients were observed for 28 days, with clinical, parasitological, and haematological assessments. RESULTS: A total of 108 patients completed the study. The overall 28-day cure rate was 88.9%. Day 28-cure rates of the three dosage schedules were 85.3%, 93.1% and 88.9% for Group A, B and C respectively. Adverse events were few and mild, the commonest being weakness and headache; there was no serious adverse event. CONCLUSION: Concerns for emergence of parasite resistance due to the use of artemisinin-naphthoquine as single dose regimen is likely to compromise the usefulness of this potentially important combination treatment. A robust multi-centre trial is recommended to evaluate a three-day regimen with potentials to achieve high cure rates while minimizing the risk of emergence of resistant parasite strains.