Statistics
Statistical analyses were performed using SAS version 9.2 (Cary, NC, USA) or higher under the UNIX operating system. For each study part, descriptive statistics were provided for demographic variables by flubentylosin dose group. Safety data were tabulated by number of subjects and percentage. PK parameters were derived from blood concentration versus time data using a noncompartmental analysis in SAS version 9.2 (Cary, North Carolina, USA). Concentration versus time data in blood and PK parameters were listed and summarized by regimen, using descriptive statistics. Planned sampling times were used in summaries and plots. If the actual sampling was within 10% or 30 minutes, whichever was smaller, of the planned time, the planned time was used for determination of the pharmacokinetic parameters. In total only ten actual times were used, two for the 0.5-hour timepoint in Part 3 and eight for the 8-hour timepoint in Part 1. In Part 1, an analysis of covariance (ANCOVA) was performed to assess dose proportionality and linear kinetics of flubentylosin. In Part 2, an ANCOVA was performed to evaluate the effect of food on the bioavailability of flubentylosin. In Part 3, an ANCOVA was performed to investigate the dose proportionality of the PK variables of flubentylosin using data on Day 7 for groups with 7 days of dosing, or Day 14 for groups with 14 days of dosing. Linear mixed-effects models were used to assess the exposure-response relationship between flubentylosin concentration and ΔΔQTcF (baseline-adjusted drug vs. placebo difference in the QT interval corrected by the Fridericia’s formula).