Phase I, Escalating, Multiple-Dose, ST-246 Safety, Tolerability and Pharmacokinetics 21-Day Trial in Healthy Volunteers (SIGA-246-002)

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ST-246; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ST-246; 250 mg, 400 mg or 800 mg of ST-246 given once daily for 21 days	Drug: ST-246; 250 mg, 400 mg or 800 mg capsules given once daily for 21 days; Other Names: Tecovirimat
PLACEBO_COMPARATOR: placebo; Placebo to match ST-246	Drug: Placebo; Capsules to match experimental drug; Other Names: Placebo to match ST-246

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Table	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.	Days 1, 6, 14-16, 21-24, 28-31, and 51-53

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax	Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data	Day 1
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax	Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data	Day 6
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax	Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data	Day 21
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax	Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles.	Day 1
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax	Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles.	Day 6
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax	Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles.	Day 21
Evaluation of Pharmacokinetic Parameters to Assess Interventions: t½	t½: Observed terminal elimination half-life determined after the last dose on Day 21	Day 21
Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau	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	Day 1
Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau	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	Day 6
Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau	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	Day 21
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Ae(0-24)	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	Day 1
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Ae(0-24)	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	Day 21

Collaborators and Investigators

• Sponsor: SIGA Technologies
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Thomas C Marbury, MD, Orlando Clinical Research

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (ACTUAL): February 1, 2008
• Study Completion (ACTUAL): February 1, 2008

Study Registration Dates

• First Submitted: February 2, 2007
• First Submitted That Met QC Criteria: February 5, 2007
• First Posted (ESTIMATE): February 6, 2007

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2017
• Last Update Submitted That Met QC Criteria: July 25, 2017
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Other Study ID Numbers: ST-246 RD PHS 1; DMID 06-0080 (OTHER: NIH Contract #: HHSN266200600014C)