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:
Information provided by:
SIGA Technologies
ClinicalTrials.gov Identifier:
NCT00431951
First received: February 2, 2007
Last updated: September 15, 2010
Last verified: September 2010
  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

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
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 October 20, 2014