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

Purpose

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.

Condition	Intervention	Phase
Orthopoxviral Disease	Drug: ST-246 400 mg Drug: ST-246 600 mg Drug: Placebo	Phase 2

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

Further study details as provided by SIGA Technologies:

Primary Outcome Measures:

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. [ Time Frame: Days 1 to 14; then 24, 48, 72, 96 and 120 hours and 4 weeks after final dose ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax [ Time Frame: Day 1 post-dose ] [ 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 14 post-dose ] [ 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 post-dose ] [ 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 14 post-dose ] [ 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: AUCtau [ Time Frame: Day 1 post-dose ] [ 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 14 post-dose ] [ 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: t½ [ Time Frame: Day 14 post-dose ] [ Designated as safety issue: No ]
t½: Observed terminal elimination half-life determined after the last dose on Day 14

Enrollment:	107
Study Start Date:	June 2009
Study Completion Date:	January 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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 Name: Tecovirimat
Placebo Comparator: Placebo Matching Placebo capsules, Orally Once Daily for 14 days	Drug: Placebo Capsules, once daily for 14 days

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

Inability to swallow study medication
Pregnant or breast-feeding
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,
History of drug allergy that contraindicates study participation
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)
Clinically abnormal ECG
Has or will participate in a clinical trial or experimental treatment within 30 days of, or during, the study
Cannot or will not do physical exercise 24 hrs before and after PK days
Will not consume grapefruit/grapefruit juice during study
Vaccination within 2 wks of screening, or planned before Day 42 of study
Treatment with prednisone or equivalent immunosuppressant/modulatory drug <3 mths before screening
Clinically significant physical exam and lab results <2weeks from 1st study drug dose

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00907803

Locations

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

Sponsors and Collaborators

SIGA Technologies

National Institutes of Health (NIH)

Investigators

Principal Investigator:	Thomas Marbury, MD	Orlando Clinical Research Center
Principal Investigator:	Erik Ross, MD	Apex Research Institute
Principal Investigator:	Jon Ruckle, MD	Hawaii Clinical Research Center

More Information

No publications provided

Responsible Party:	Annie Frimm, Vice President Regulatory Affairs, SIGA Technologies, Inc.
ClinicalTrials.gov Identifier:	NCT00907803 History of Changes
Other Study ID Numbers:	SIGA-246-004, DMID 08-0055
Study First Received:	May 21, 2009
Results First Received:	July 29, 2010
Last Updated:	September 15, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by SIGA Technologies:

Orthopoxvirus
Smallpox
This is a safety study only
ST-246 is being studied for treatment of Orthopoxviruses

ClinicalTrials.gov processed this record on May 23, 2013

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