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

This study has been completed.
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:
SIGA Technologies
ClinicalTrials.gov Identifier:
NCT00431951
First received: February 2, 2007
Last updated: September 15, 2010
Last verified: September 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Healthy
 Drug: ST-246
Drug: Placebo
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by SIGA Technologies:

Primary Outcome Measures:
  • 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 [ Time Frame: Days 1, 6, 14-16, 21-24, 28-31, and 51-53 ] [ Designated as safety issue: No ]

    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:
  • Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data

  • Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
    Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data

  • Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data

  • Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles.

  • Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
    Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles.

  • Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles.

  • Evaluation of Pharmacokinetic Parameters to Assess Interventions: t½ [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    t½: Observed terminal elimination half-life determined after the last dose on Day 21

  • Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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: AUCtau [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
    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: AUCtau [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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

  • Evaluation of Pharmacokinetic Parameters to Assess Interventions: Ae(0-24) [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    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


Enrollment: 30
Study Start Date: February 2007
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Tecovirimat
Placebo Comparator: placebo
Placebo to match ST-246
 Drug: Placebo
Capsules to match experimental drug
Other Name: Placebo to match ST-246

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00431951

Locations
United States, Florida
Orlando Clinical Research
Orlando, Florida, United States, 32809
Sponsors and Collaborators
SIGA Technologies
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Thomas C Marbury, MD Orlando Clinical Research
  More Information

No publications provided

Responsible Party: Dennis Hruby, SIGA Technologies, Inc.
ClinicalTrials.gov Identifier: NCT00431951     History of Changes
Other Study ID Numbers: ST-246 RD PHS 1, DMID 06-0080
Study First Received: February 2, 2007
Results First Received: May 29, 2009
Last Updated: September 15, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by SIGA Technologies:
Healthy Volunteers

ClinicalTrials.gov processed this record on May 23, 2013