AAC Accepts, published online ahead of print on 3 March 2008

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Antimicrob. Agents Chemother. doi:10.1128/AAC.01303-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Single-Dose Safety and Pharmacokinetics of ST-246, a novel orthopoxvirus egress inhibitor

Robert Jordan, Deborah Tien, Tove' C. Bolken, Kevin F. Jones, T. R. Shanthakumar, Josef Strasser, Annie Frimm, Michael L. Corrado, Phoebe G. Strome, and Dennis E. Hruby^*

SIGA Technologies, Corvallis, Oregon; TransTech Pharma, Inc., High Point, North Carolina; INC Research, Raleigh, North Carolina

^* To whom correspondence should be addressed. Email: dhruby{at}sgph.com.

ST-246 is a novel, potent orthopoxvirus egress inhibitor that is being developed to treat pathogenic orthopoxvirus infections of humans. This phase I, double-blind, randomized, placebo-controlled single ascending dose study (first time with humans) was conducted to determine safety, tolerability, and pharmacokinetics of ST-246 in healthy volunteers. ST-246 was administered in single oral doses of 500, 1000, and 2000 mg to fasting healthy volunteers and 1000 mg to non-fasting healthy volunteers. ST-246 was generally well tolerated with no serious adverse events (SAEs), and no subject was withdrawn due to ST-246. The most commonly reported drug-related AE was neutropenia that was found, upon further analysis, not to be treatment related. ST-246 was readily absorbed following oral administration with mean times to maximum concentration from 2 h to 3 h. Absorption was greater in non-fasting volunteers compared to fasting volunteers. Administration of ST-246 resulted in exposure levels predicted to be sufficient for inhibiting orthopoxvirus replication when compared to exposure levels in non-human primates in which ST-246 protected animals from lethal orthopoxvirus infection.

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