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Antimicrobial Agents and Chemotherapy, May 2008, p. 1721-1727, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01303-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Single-Dose Safety and Pharmacokinetics of ST-246, a Novel Orthopoxvirus Egress Inhibitor{triangledown}

Robert Jordan,1 Deborah Tien,1,{dagger} Tove' C. Bolken,1 Kevin F. Jones,1 Shanthakumar R. Tyavanagimatt,1 Josef Strasser,2 Annie Frimm,3 Michael L. Corrado,3 Phoebe G. Strome,3 and Dennis E. Hruby1*

SIGA Technologies, Corvallis, Oregon,1 TransTech Pharma, Inc., High Point, North Carolina,2 INC Research, Raleigh, North Carolina3

Received 9 October 2007/ Returned for modification 24 January 2008/ Accepted 23 February 2008

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 the safety, tolerability, and pharmacokinetics of ST-246 in healthy human volunteers. ST-246 was administered in single oral doses of 500, 1,000, and 2,000 mg to fasting healthy volunteers and 1,000 mg to nonfasting healthy volunteers. ST-246 was generally well tolerated with no serious adverse events, and no subject was withdrawn from the study due to ST-246. The most commonly reported drug-related adverse event was neutropenia, which 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 nonfasting volunteers than in fasting volunteers. Administration of ST-246 resulted in exposure levels predicted to be sufficient for inhibiting orthopoxvirus replication compared to exposure levels in nonhuman primates in which ST-246 protected animals from lethal orthopoxvirus infection.

* Corresponding author. Mailing address: SIGA Technologies, Inc., 4575 SW Research Way, Corvallis, OR 97330. Phone: (541) 753-2000. Fax: (541) 753-9999. E-mail: dhruby{at}sgph.com

{triangledown} Published ahead of print on 3 March 2008.

{dagger} Present address: Baxter Healthcare Corp., Thousand Oaks, CA.

Antimicrobial Agents and Chemotherapy, May 2008, p. 1721-1727, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01303-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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