Safety, tolerability and pharmacokinetics of AFN-1252 administered as immediate release tablets in healthy subjects

• Published in: Future microbiology Vol. 10; no. 11; pp. 1805 - 1813
• Main Authors: Hafkin, Barry, Kaplan, Nachum, Hunt, Thomas L
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2015
• Subjects: Administration, Oral; Adolescent; Adult; AFN-1252; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - pharmacokinetics; Benzofurans - administration & dosage; Benzofurans - adverse effects; Benzofurans - pharmacokinetics; Consent; Dosage; Double-Blind Method; Drug dosages; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; FabI inhibitor; Female; Healthy Volunteers; Humans; immediate release; Male; Middle Aged; Oral administration; Pharmacokinetics; Phase I; Placebos - administration & dosage; Plasma; Pyrones - administration & dosage; Pyrones - adverse effects; Pyrones - pharmacokinetics; safety; Staphylococcus infections; Studies; Tablets - administration & dosage; Tablets - adverse effects; Tablets - pharmacokinetics; Young Adult; United States > US; FabI inhibitor; Phase I; AFN–1252; safety; pharmacokinetics; immediate release; Staphylococcus aureus
• ISSN: 1746-0913; 1746-0921
• DOI: 10.2217/fmb.15.101

AFN-1252 is a novel inhibitor of FabI, an essential enzyme in spp. This study was undertaken to assess the safety, tolerability and pharmacokinetic properties of AFN-1252, following oral administration in an ascending dose trial. 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. 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. 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.