title: Safety and pharmacokinetics of the anti-orthopoxvirus compound ST-246 following a single daily oral dose for 14 days in human volunteers.
abstract: ST-246 is being evaluated as a treatment for pathogenic orthopoxvirus infections in humans. To this end, a phase 2, double-blind, randomized, placebo-controlled, multicenter trial was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of ST-246 when administered as a single daily oral dose (400 mg or 600 mg) for 14 days in fed adult volunteers. ST-246 was safe and well tolerated, with no deaths or serious adverse events reported during the study. There was a low incidence of treatment-emergent adverse events (TEAEs), the most common of which were mild nausea and headache. There were no clinically significant results from laboratory assessments, vital sign measurements, physical examinations, or electrocardiograms. The PK and dose proportionality of ST-246 were determined. The PK analysis showed that steady state was achieved by day 5 for the ST-246 400-mg treatment group and by day 6 for the 600-mg group. The dose proportionality analysis showed that the 400- and 600-mg ratio of dose-normalized peak drug concentration in plasma (C(max)) and relative exposure for each dosing interval (AUC(τ)) ranged from 80% to 85%. However, the 90% confidence intervals did not include 1.0, so dose proportionality could not be concluded. Overall, ST-246 was shown to be safe, and the PK was predictable. These results support further testing of ST-246 in a multicenter pivotal clinical safety study for licensure application.
authors: SIGA Technologies, Corvallis, Oregon, USA.
authors: Jarasvech
authors: J
authors: Chinsangaram
authors: Kady M
authors: KM
authors: Honeychurch
authors: Shanthakumar R
authors: SR
authors: Tyavanagimatt
authors: Janet M
authors: JM
authors: Leeds
authors: Tove' C
authors: TC
authors: Bolken
authors: Kevin F
authors: KF
authors: Jones
authors: Robert
authors: R
authors: Jordan
authors: Thomas
authors: T
authors: Marbury
authors: Jon
authors: J
authors: Ruckle
authors: Denis
authors: D
authors: Mee-Lee
authors: Eric
authors: E
authors: Ross
authors: Israel
authors: I
authors: Lichtenstein
authors: Margaret
authors: M
authors: Pickens
authors: Michael
authors: M
authors: Corrado
authors: Jean M
authors: JM
authors: Clarke
authors: Annie M
authors: AM
authors: Frimm
authors: Dennis E
authors: DE
authors: Hruby
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D054833:Isoindoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D010797:Phthalimides
chemical_list: D000998:Antiviral Agents; D001549:Benzamides; D054833:Isoindoles; D010919:Placebos; C505045:tecovirimat; D010797:Phthalimides