We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Determination of the Optimal Single Dose Treatment for Acoziborole, a Novel Drug for the Treatment of Human African Trypanosomiasis: First-in-Human Study.
- Authors
Tarral, Antoine; Hovsepian, Lionel; Duvauchelle, Thierry; Donazzolo, Yves; Latreille, Mathilde; Felices, Mathieu; Gualano, Virginie; Delhomme, Sophie; Valverde Mordt, Olaf; Blesson, Severine; Voiriot, Pascal; Strub-Wourgaft, Nathalie
- Abstract
Background and Objectives: Acoziborole is a novel boron-containing candidate developed as an oral drug for the treatment of human African trypanosomiasis (HAT). Results from preclinical studies allowed progression to Phase 1 trials. We aimed to determine the best dose regimen for all stages of HAT. Methods: Acoziborole was assessed in 128 healthy adult males of sub-Saharan African origin living in France. The study included a single oral administration of a 20- to 1200-mg dose in a randomised double-blind study in cohorts of 8 (6 active, 2 placebo) to assess safety, tolerability, and pharmacokinetics. In three additional open cohorts of 6 participants, the effect of activated charcoal was evaluated, bioequivalence of capsules versus tablets was assessed, and safety in the 960-mg tablet cohorts was monitored. Results: Acoziborole was well tolerated at all doses tested; no dose-related adverse events were observed. The drug appeared rapidly in plasma (at 1 h), reached tmax between 24 and 72 h, and remained stable for up to 96 h, after which a slow decrease was quantifiable until 14 weeks after dosing. Charcoal had little impact on the enterohepatic recirculation effect, except for the 20-mg dose. Bioequivalence between capsule and tablet formulations was demonstrated. The therapeutic single dose for administration under fasted conditions was fixed to 960 mg. The maximum administered dose was 1200 mg. Conclusions: This study showed that acoziborole could be safely assessed in patients as a potential single-dose oral cure for both stages of gambiense HAT. Trial Registration: The study was registered with ClinicalTrials.gov: NCT01533961.
- Subjects
FRANCE; AFRICAN trypanosomiasis; THERAPEUTIC equivalency in drugs; ORAL drug administration; SUMATRIPTAN; ACTIVATED carbon; ORAL medication
- Publication
Clinical Pharmacokinetics, 2023, Vol 62, Issue 3, p481
- ISSN
0312-5963
- Publication type
Article
- DOI
10.1007/s40262-023-01216-8