Safety, Tolerability, Pharmacokinetics (PK) of the Anti-Orthopox Drug, ST-246 (246-Safety)

Double-Blind, Randomized, Placebo-Controlled, Multi-Center Trial to Assess Safety, Tolerability, and PK of the Anti-Orthopoxvirus Compound ST-246 When Administered as a Single Daily Oral Dose for 14 Days in Volunteers in the Fed State

The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of two clinical doses of the anti-orthopoxvirus drug, ST-246, administered as a single daily oral dose for 14 days to healthy, fed volunteers. The results of this trial determine which dose will be used in expanded pivotal safety trials.

Study Overview

• Status: Completed
• Conditions: Orthopoxviral Disease
• Intervention / Treatment: Drug: ST-246 400 mg; Drug: ST-246 600 mg; Drug: Placebo

Detailed Description

This study is a Phase II, double-blind, randomized, placebo-controlled, multi-center (3 sites) trial to assess the safety, tolerability, and pharmacokinetics of 400 mg and 600 mg Form I ST-246 when administered as a single daily oral dose for 14 days to 107 healthy, fed volunteers between 18 and 74 years of age. Safety parameters included adverse events, vital signs, physical examinations, laboratory tests (hematology, blood chemistry, and urinalysis) and electrocardiograms.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Ana, California, United States, 92705
      • Apex Research Institute
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 - 75 yrs
2. Healthy volunteer
3. Ability to consent
4. Available for clinical follow-up for study
5. Not taking other medications
6. Adequate venous access
7. Using adequate birth control; negative pregnancy test
8. Able and willing to avoid alcohol for screening and study duration

Exclusion Criteria:

1. Inability to swallow study medication
2. Pregnant or breast-feeding
3. Medical condition, e.g., asthma, hypertension, angioedema, traumatic brain injury other than concussion, bleeding disorder, blood dyscrasia, idiopathic seizures, cardiac disease that limits activity, diabetes, active malignancy, Hepatitis B or C, HIV or AIDS, chronic microbial infection,
4. History of drug allergy that contraindicates study participation
5. Medical, psychiatric, social, occupational or other reason that jeopardizes the safety/rights of participant or renders he/she unable to comply with the protocol (including drug or alcohol abuse, or homelessness)
6. Clinically abnormal ECG
7. Has or will participate in a clinical trial or experimental treatment within 30 days of, or during, the study
8. Cannot or will not do physical exercise 24 hrs before and after PK days
9. Will not consume grapefruit/grapefruit juice during study
10. Vaccination within 2 wks of screening, or planned before Day 42 of study
11. Treatment with prednisone or equivalent immunosuppressant/modulatory drug <3 mths before screening
12. Clinically significant physical exam and lab results <2weeks from 1st study drug dose

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ST-246 400 mg; ST-246 400mg (2 x 200 mg Capsules) Orally Once Daily for 14 days	Drug: ST-246 400 mg; Capsules, 400 mg daily for 14 days; Other Names: Tecovirimat
Experimental: ST-246 600 mg; ST-246 600 mg (3 x 200 mg Capsules) Orally Once Daily for 14 days	Drug: ST-246 600 mg; Capsules, 600 mg daily for 14 days; Other Names: Tecovirimat
Placebo Comparator: Placebo; Matching Placebo capsules, Orally Once Daily for 14 days	Drug: Placebo; Capsules, once daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Study Participants Who Tolerated a Single Daily Oral ST-246 Dose as Determined by Safety Parameter Changes According to the DAIDS (Division of Acquired Immunodeficiency Syndrome) Adverse Events (AE) Grading Table.	Subjects were administered a single, daily oral dose of ST-246 (400 or 600 mg)and changes in safety parameteres were monitored. Safety parameters included adverse events, vital signs, physical examinations, laboratory tests (hematology, blood chemistry, and urinalysis) and electrocardiograms. The DAIDS AE grading table is a list of common terms and severity (intensity) of parameters used to describe adverse events occurring in NIAID-sponsored clinical studies/trials.	Days 1 to 14; then 24, 48, 72, 96 and 120 hours and 4 weeks after final dose

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 post-dose
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax	Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data	Day 14 post-dose
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 post-dose
Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax	Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles	Day 14 post-dose
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 post-dose
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 14 post-dose
Evaluation of Pharmacokinetic Parameters to Assess Interventions: t½	t½: Observed terminal elimination half-life determined after the last dose on Day 14	Day 14 post-dose

Collaborators and Investigators

• Sponsor: SIGA Technologies
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Erik Ross, MD, Apex Research Institute; Principal Investigator: Jon Ruckle, MD, Hawaii Clinical Research Center

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: May 21, 2009
• First Submitted That Met QC Criteria: May 22, 2009
• First Posted (Estimate): May 25, 2009

Study Record Updates

• Last Update Posted (Estimate): September 21, 2010
• Last Update Submitted That Met QC Criteria: September 15, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Smallpox; Orthopoxvirus; This is a safety study only; ST-246 is being studied for treatment of Orthopoxviruses
• Other Study ID Numbers: SIGA-246-004; DMID 08-0055 (Other Identifier: NIH Contract: HHSN261002600014C)