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

Abstract

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.

• Authors: Barry Hafkin, Nachum Kaplan, Thomas L Hunt
• Journal: Future microbiology (Future Microbiol) Vol. 10 Issue 11 Pg. 1805-13 ( 2015) ISSN: 1746-0921 [Electronic] England
• PMID: 26357940 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• API 1252
• Anti-Bacterial Agents
• Benzofurans
• Placebos
• Pyrones
• Tablets

Topics

• Administration, Oral
• Adolescent
• Adult
• Anti-Bacterial Agents (administration & dosage, adverse effects, pharmacokinetics)
• Benzofurans (administration & dosage, adverse effects, pharmacokinetics)
• Double-Blind Method
• Drug-Related Side Effects and Adverse Reactions (epidemiology, pathology)
• Female
• Healthy Volunteers
• Humans
• Male
• Middle Aged
• Placebos (administration & dosage)
• Pyrones (administration & dosage, adverse effects, pharmacokinetics)
• Tablets (administration & dosage, adverse effects, pharmacokinetics)
• Young Adult