Study procedures.

The study was performed on an inpatient basis, and in each treatment period, subjects were admitted to the clinical site on day −2, 2 days before the day of dosing (day 1), and were discharged after completion of safety procedures on the day after dosing (day 2). The washout between consecutive study periods was ≥7 days. Study treatment was administered with subjects in the fasting state in the morning of day 1.

In treatment period 1, continuous 12-lead ECG data were recorded for 24 h on day −1, and subjects underwent a graded exercise test using a modified Bruce protocol with a target heart rate of >90 bpm 24 h and 25 min before dosing. On day 1 in all treatment periods, a continuous 12-lead ECG recording procedure was performed from 1.5 h before dosing to 24 h after dosing. The 12-lead ECGs were extracted in triplicate at three time points (1.5, 1.0, and 0.5 h) before dosing and at 20, 35, 50, and 65 min and 1.5, 2, 4, 6, 12, 18, and 22 h after dosing. ECG intervals were measured by a central ECG laboratory with a semiautomated technique.

Blood samples were obtained before dosing, at time points similar to those used for the postdose ECG extractions, and at 48, 72, and 96 h after the dose to measure omadacycline plasma levels and determine pharmacokinetic parameters, including C_max, time to maximum concentration, and AUC_0–24h. Blood samples were obtained 5 min after each time point indicated for ECG measurement.