Safety and pharmacokinetics of the anti-orthopoxvirus compound ST-246 following a single daily oral dose for 14 days in human volunteers.

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.

Contribution of a heating element to topical anesthesia patch efficacy prior to vascular access: results from two randomized, double-blind studies.

CONTEXT: Pain associated with superficial procedures, including intravenous (IV) access procedures, should be prevented when possible, especially in children. OBJECTIVES: To evaluate a topical local anesthetic patch containing lidocaine 70 mg/tetracaine 70 mg with a heating element designed to warm the skin and facilitate rapid delivery of local anesthetics into the skin. The pilot study was designed to provide data to inform the design of the definitive study to evaluate the impact of controlled heat on the efficacy of the lidocaine/tetracaine patch (patch) when applied before IV cannulation. METHODS: Subjects in the pilot study were randomized to eight groups that varied by heated vs. unheated patch, 20 vs. 30 minute application, and 16 vs. 18 G catheter. Subjects in the definitive study were randomized in a double-blind manner to receive either the heated or unheated patch, 20 minutes before vascular access, using a 16 G catheter in the antecubital space of the arm. In both studies, the primary efficacy measure was subject-reported pain intensity using a visual analog scale. RESULTS: Pilot study: Subjects who received the heated patch (n=43) vs. the unheated patch (n=37) had lower mean pain intensity scores (14.7 vs. 23.5mm, P=0.04). Pain intensity scores did not differ significantly by application time, but the difference between the 16 and 18 G catheter groups approached statistical significance (22.8 vs. 14.9 mm, P=0.05). Definitive study: Mean pain intensity scores for the heated patch group (n=124) vs. the unheated patch group (n=126) were 14.2 and 20.5mm, respectively (P=0.006). CONCLUSION: Heated patches provided significantly better pain relief compared with unheated patches. All the subjects tolerated the patches well, with few adverse effects.