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Phase I, Escalating, Multiple-Dose, ST-246 Safety, Tolerability and Pharmacokinetics 21-Day Trial in Healthy Volunteers

Phase 1
Completed
Conditions
Healthy
Interventions
Drug: Placebo
Registration Number
NCT00431951
Lead Sponsor
SIGA Technologies
Brief Summary

The 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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
ST-246ST-246250 mg, 400 mg or 800 mg of ST-246 given once daily for 21 days
placeboPlaceboPlacebo to match ST-246
Primary Outcome Measures
NameTimeMethod
Number of Study Participants Who Tolerated ST-246 (250, 400 or 800mg) as Determined by Changes in Safety Parameters, According to the Division of Acquired Immunodeficiency Syndrome (DAIDS) Adverse Events (AE) Grading TableDays 1, 6, 14-16, 21-24, 28-31, and 51-53

Evaluated safety parameters included:

1. physical examination/vital signs

2. electrocardiograms (heart rate, PR interval, QRS duration, QT interval, and QTc Bazett)

3. laboratory safety tests (hematology, chemistry, urinalysis)

4. 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.

Secondary Outcome Measures
NameTimeMethod
Evaluation of Pharmacokinetic Parameters to Assess Interventions: CmaxDay 21

Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data

Evaluation of Pharmacokinetic Parameters to Assess Interventions: TmaxDay 21

Tmax: Time to reach maximum drug concentration in plasma calculated from \[plasma\] versus time profiles.

Evaluation of Pharmacokinetic Parameters to Assess Interventions: t½Day 21

t½: Observed terminal elimination half-life determined after the last dose on Day 21

Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtauDay 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

Evaluation of Pharmacokinetic Parameters to Assess Interventions: Ae(0-24)Day 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

Trial Locations

Locations (1)

Orlando Clinical Research

🇺🇸

Orlando, Florida, United States

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