Double-Blind Randomized Crossover Trial to access Electrocardiogram Effects of HPN-100
Study Details
Arm 1:
Primary Objective:
• To determine the safety and tolerability of multiple ascending, supratherapeutic doses of HPN-100.
Arm 2:
Primary Objective:
• To assess the effects of steady-state levels of HPN-100 metabolites (4 phenylbutyric acid [PBA], phenylacetic acid [PAA], and phenylacetylglutamine [PAGN]) on 12-lead electrocardiogram (ECG) parameters in healthy male and female subjects with the primary endpoint being the time-matched change from baseline in the QT interval corrected for heart rate (HR) based on an individual correction method (QTcI).
Protocol Summary
Safety and tolerability as measured by the rate and severity of adverse events in each treatment group.
Timeframe: 3-day treatment period
Changes from baseline QTcI as a measure of effects of study-state HPN-100 metabolites: PBA, PAA, and PAGN
Timeframe: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
Correlate time-matched ECG waveform changes to steady-state levels of HPN-100 by using QTcB and QTcF formulas to assess ECG morphologic changes.
Timeframe: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
Correlate time-matched QTcI change from baseline and serum levels of PBA, PAA, and PAGN drawn on Day 1, Day 2, Day 3, and Day 4
Timeframe: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
Gender differences in metabolism of HPN-100 as measured by time-matched serum levels of HTN-100, PBA, PAA, and PAGN via samples drawn on Day 1, Day 2, Day 3, and Day 4.
Timeframe: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
Number and severity of adverse events in each treatment group.
Timeframe: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments