Determination of Optimal Dosing Duration for Cotrimoxazole, Ciprofloxacin, Clarythromycin, And Tinidazole, Novel Oral Drugs for The Treatment of T.B.Gambiense Human African Trypanosomiasis: First-In-Human Studies

Abstract

Background and Objectives: Fexinidazole is a 5-nitroim-idazole recently included in a clinical efficacy trial as an oral drug for the treatment of human African trypanoso-miasis (HAT). Preclinical studies showed it acts as a pharmacologically active prodrug with two key active metabolites: sulfoxide and sulfone (the most active metab- olite). The present studies aimed to determine other oral antibiotic regimen for the treatment of stage 2 sleeping sickness which could eventually also treat stage 1 patients, like Fexinidazole. Cotrimoxazole 960 mgs twice daily for two weeks, or one month if unsuccessful at two weeks of treatment; clarithromycin 250 mgs twice daily and tinidazole 500 mgs twice daily for one week or two weeks; and ciprofloxacin 500mgs twice daily for two weeks were administered. Methods: Cotrimozaxole, ciprofloxacin, clarithromycin, and tinidazole were assessed in 99 HAT positive children and adult male and female subjects of sub-Saharan African origin. Three initial first-in-human studies and two additional studies assessed a weekly, two weekly and monthly doses of the above drugs. Cotrimoxazole 960 mgs twice daily for two weeks, or one month if unsuccessful at two weeks of treatment; clarithromycin 250 mgs twice daily and tinidazole 500 mgs twice daily for one week or two weeks; and ciprofloxacin 500mgs twice daily for two weeks were administered. Results: The drugs were well-tolerated in the various doses. Conclusion: These studies show that cotrimoxazole, ciprofloxacin, clarithromycin and tinidazole can be safely assessed in patients as potential oral cure for both stages of Human African Trypanasomiasis.