Title
Phase I, Escalating, Multiple-Dose, ST-246 Safety, Tolerability and Pharmacokinetics 21-Day Trial in Healthy Volunteers
Double-blind, Randomized, Placebo-controlled, Escalating, Multiple-dose, Phase I Trial to Assess Safety, Tolerability and Pharmacokinetics of ST-246 Administered as a Single Daily Dose for 21 Days in Healthy, Non-fasted Volunteers
Phase
Phase 1Lead Sponsor
SIGA TechnologiesStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
HealthyIntervention/Treatment
tecovirimat ...Study Participants
30The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of a single, daily, oral dose of ST-246 (either 250, 400 or 800mg) administered for 21 days to 30 healthy, fed volunteers.
This was a double-blind, placebo-controlled, dose-escalating, multiple-dose study of orally administered ST-246 to 30 healthy volunteers ages 18-50 years, randomized to receive either active drug (8 subjects) or placebo (2 subjects) in 1 of 3 dosing groups (250, 400 or 800mg groups). Each dose group of 10 was divided into two cohorts of 5 subjects (4 active and 1 placebo). The first cohort was dosed approximately 4-8 weeks before the second cohort of each dose group. Dose groups completed the study treatment approximately 5 weeks prior to the start of the following dose group. Study procedures included several overnight stays, medical history/exam, laboratory testing done by blood draw, and electrocardiograms.
250 mg, 400 mg or 800 mg capsules given once daily for 21 days
Capsules to match experimental drug
Subject Inclusion Criteria: Healthy volunteers Ability to Consent Not taking any other medication Adequate venous access Using adequate birth control Subject Exclusion Criteria: Inability to swallow study medication. Pregnant or breastfeeding Received experimental drug within 30 days of study entry or will participate in any experimental study during the study period. Current drug abuse, alcohol abuse, or homelessness. Taking concomitant medication Lactose Intolerance Medical condition; e.g., asthma, diabetes, thyroid disease, angioedema, BMI >35 or <18, hypertension, bleeding disorder, malignancy, seizure, neutropenia, Hepatitis B or C, HIV or AIDS. Any condition, occupational reason or other responsibility that, in the judgment of the Investigator, would jeopardize the safety or rights of a volunteer, or render the subject unable to comply with the protocol
| Event Type | Organ System | Event Term | ST-246 250 mg | ST-246 400mg | ST-246 800 mg | Placebo |
|---|
Evaluated safety parameters included: physical examination/vital signs electrocardiograms (heart rate, PR interval, QRS duration, QT interval, and QTc Bazett) laboratory safety tests (hematology, chemistry, urinalysis) adverse events (AEs) For a)-c), statistical values (mean, standard deviation, median, minimum, maximum) and changes from baseline (Day 1 pre-dose) to each time-point, were compared to laboratory normal reference ranges. If values for a)-d) were a Grade 3 or higher (in DAIDS AE Table)and ST-246-related, they were considered severe and significant, respectively.
Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data
Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data
Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data
Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles.
Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles.
Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles.
t½: Observed terminal elimination half-life determined after the last dose on Day 21
AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule
AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule
AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule
Ae(0-24): Cumulative amount of drug excreted unchanged in urine over 24 hours (three 8-hour collection periods), determined on Days 1 and 21
Ae(0-24): Cumulative amount of drug excreted unchanged in urine over 24 hours (three 8-hour collection periods), determined on Days 1 and 21
