Study Objectives and Outcomes

The primary study objective was to determine if ANS-6637, given in combination with midazolam, a sensitive substrate for CYP3A, would result in a clinically significant drug-drug interaction (DDI) of sufficient magnitude to warrant dose-adjustment for other agents that are predominantly metabolized by CYP3A when coadministered with ANS-6637. The interaction was considered clinically significant if the 90% confidence interval (CI) for the geometric mean ratio (GMR) of midazolam exposure (AUC_0-∞, C_max) with and without ANS-6637 coadministration was not contained entirely within the prespecified no-effect range of 0.7-1.43. Secondary objectives were to describe the multidose steady-state pharmacokinetics of ANS-6637 and GS-548351 and to evaluate the safety and tolerability of ANS-6637 when given alone or in combination with midazolam in healthy volunteers.