The results of I phase clinical study of class III antiarrhythmic drug, tablet form

Abstract

Aim: To evaluate the safety and tolerance of single dose or repeated doses administration of domestic class III antiarrhythmic agent Refralon (cavutilide), tablets, by healthy volunteers; and to study it’s pharmacokinetics and absolute bioavailability.Material and Methods. Healthy male volunteers, aged 18 – 45 years were included in one of 7 cohorts: 1, 2, 4 и 6 mg PO, 1 mg IV (these cohorts included 6 people each), one cohort of 12 people who took 2 mg of the drug per day for 5 days, and one cohort of 6 menfor 10 days. Drug intake/injection, blood and urine tests, sampling for pharmacokinetic analysis, assessment of vital signs, ECG registration at specified points, Holter monitoring of ECG were performed in a hospital setting.Results. The study included 48 volunteers 32 ± 7,2 years old, mean weight 74,6 ± 4,7 kg. No significant changes in blood and urine tests and vital signs in any of cohorts were registered. Among cohorts of single dose oral intake only maximum dose of 6 mg caused persistent statistically significant increase of the duration of the QT and QTc intervals. In cohort of multiple intake of 2 mg of the drug statistically significant increase of the QT/QTc duration was noted with maximum value on 9-10 days. By this time balance between absorption and elimination processes was achieved.Conclusion. Duration of the QT/QTc intervals didn’t exceed reference values during the entire study in all cohorts of oral intake of Refralon, either single dose or repeated doses administration. Significant persistent increase of the duration of the QT and QTc intervals was registered only in cohort of maximum single dose of 6 mg intake and during intake of 2 mg of Refralon daily for 5-10 days. Stationary state was achieved by 8-10 day of Refralon intake.