Electrocardiograms. A 12-lead ECG will be obtained after the subject has been in the supine position for at least 10 minutes at the time points indicated in the schedule of events (Table 9-1). On Days 1, 4, and 7, an ECG will be recorded 4 hours after the AM study drug administration. The acceptable window for collection from the scheduled collection time point will ±15 minutes. Electrocardiogram assessments will include comments on whether the tracings are normal or abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, any evidence of myocardial infarction, or ST segment, T wave, and U wave abnormalities. In addition, the following parameters will be measured and reported: heart rate; PR, RR, and QT intervals; QTcF; QT interval corrected using Bazett’s formula; and QRS duration. All ECGs must be performed by an experienced ECG technician. The investigator will determine whether any of the 12-lead ECG results are clinically significant or not clinically significant. Clinical significance is defined as any variation in results that has medical relevance and may result in an alteration in medical care (eg, active observation, diagnostic measures, or therapeutic measures). If a clinically significant change from screening is noted, the clinically significant value and reason for clinical significance will be documented on the AE page of the subject’s eCRF. The investigator will continue to monitor the subject with additional assessments until either the values have reached reference range or the values at screening or until the investigator determines that follow-up is no longer medically necessary.
Electrocardiograms. All ECGs will be measured after the subject has been in the supine position for at least 5 minutes. A single repeat measurement is permitted at screening for eligibility determination. Electrocardiogram assessments will include comments on whether the tracings are normal or abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, any evidence of myocardial infarction, or ST-segment, T-wave, and U-wave abnormalities. In addition, measurements of the following intervals will be measured and reported: RR interval, PR interval, QRS width, QT interval, and QTcF. Single Dose (Part 1): Single 12-lead ECG recordings will be made at screening and check-in; at 6, 12, and 24 hours after dosing; on Day 4; prior to discharge on Day 8 (healthy subjects) or Day 11 (hepatically impaired subjects); and at EOS. Single 12-lead ECG recordings will be made at screening and check-in; on Days 4, 8, and 12; and at EOS.
