Safety, tolerability and pharmacokinetics of AFN-1252 administered as immediate release tablets in healthy subjects
Barry Hafkin1, Nachum Kaplan1, Thomas L Hunt2
1Nobelex Biotech, MaRS Centre, South Tower, 101 College Street, Suite 300, Toronto, ON M5G 1L7, Canada.
Aims:
AFN-1252 is a novel inhibitor of FabI, an essential enzyme in Staphylococcus spp. This study was undertaken to assess the safety, tolerability and pharmacokinetic properties of AFN-1252, following oral administration in an ascending dose trial.
Materials & Methods:
This was a double-blind, randomized, placebo-controlled, two-part study. In Part I, single doses (QD) of 100, 200, 300, or 400 mg AFN-1252 were administered. In Part II, subjects received 200, 400, 600, or 800 mg (total daily dose) where 100, 200 and 400-mg doses were given twice in one day.
Results:
AFN-1252 was well-absorbed with Cmax at 3-4 h when given once per day and 2.5-9 h when dosed twice in a single dosing day. T½ ranged from 8 to 11 h. Total and peak exposures of AFN-1252 increased nonlinearly. Adverse events were primarily mild and resolved promptly.
Conclusions:
Oral doses of AFN-1252 were safe and well tolerated. AFN-1252 has the potential for once or twice-a-day dosing for treatment of staphylococcal infections.
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