Near-thorough QT study as part of a first-in-man study

Abstract

Detailed electrocardiographic (ECG) support was provided to a first-in-man, single-ascending-dose study that included 6 cohorts of 8 male volunteers each. In each cohort, 6 and 2 subjects received active compound and placebo, respectively. Long-term 12-lead ECGs were obtained on baseline day -1, dosing day 1, and day 2. Automatic QT-interval measurements were made at 63 time points (28 at baseline and 35 on treatment). Based on QT/RR distribution, 20% of measurements were visually verified. Baseline-corrected time-matched DeltaQTc values were obtained at 35 postdose time points. Placebo subjects of all cohorts were pooled. When 2 cohorts of the lowest, middle, and highest doses were pooled (12 subjects per active treatment group), the spreads of placebo-corrected DeltaDeltaQTc values were within the regulatory requirements (single-sided 95% confidence interval <10 milliseconds) at all time points. Thus, this ECG support of the first-in-man study provided data of regulatory acceptable accuracy at a small fraction of the cost of a full thorough QT study.