*3.3.2 Phase I trials*

Phase I first-in-human (FIH) studies are typically done in healthy adult volunteers. The dosing regimen, the initial human starting dose, and dose escalation scheme will be based on preclinical efficacy and adequate safety margin considerations. The usual aim is to establish either a maximum tolerated dose or a minimum biologically active dose. A comprehensive outline of the framework and general considerations for the design of FIH studies is provided by Shen et al. [55]. Although initial testing of novel drug candidates has also been conducted in seropositive patients with HIV, HBV, and HCV, this has rarely been done in Chagas disease. As of December 2021, several phase I studies in patients with Chagas disease for formulation bioequivalence, drug interactions, or drug repurposing were listed in the WHO International Clinical Trials Registry Platform (ICTRP) [56] and ClinicalTrials.gov database [57], but no FIH studies were found. Given the need to establish new and robust pharmacodynamic markers, opportunities to conduct FIH studies in populations of chronic indeterminate disease may be considered.
