2.8. Dog Cardiovascular Safety Pharmacology Study

This study was performed in accordance with Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, 2001, guidance for Industry: S7 A Safety Pharmacology Studies for Human Pharmaceuticals, to evaluate the potential cardiovascular effects of PF614 in telemetered animals by oral gavage. Four naïve male and four naïve female beagle dogs (Covance Research Products, Cumberland, Virginia) that had been surgically implanted with an electrocardiogram (ECG), blood pressure and temperature transmitter and allowed at least 40 days of recovery were given four doses via oral gavage of the vehicle control (0.1 N hydrochloric acid in reverse osmosis water) or 2, 6, or 18 mg/kg of PF614 at a dose volume of 5 mL/kg in a Latin square dosing design (Table 3). Assessment of cardiovascular function was based on qualitative and quantitative (PR, QT, and heart-rate corrected QT [QTc] intervals and QRS duration) ECG evaluation, as well as quantitative analysis of hemodynamic parameters (heart rate; arterial pulse pressure; and systolic, diastolic, and mean arterial pressures). Telemetry data were continuously recorded for at least 90 minutes prior to dosing and through at least 49 hours postdose on each dosing day, and were analyzed and reported through 19 hours postdose. Assessment of general health of the dogs was based on mortality/moribundity, clinical observations, body weight, and body temperature.

Dog Safety Pharmacology Study