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

Phase 2

Completed

• Conditions: Orthopoxviral Disease
• Interventions: Drug: ST-246 400 mg; Drug: ST-246 600 mg; Drug: Placebo

• Registration Number: NCT00907803
• Lead Sponsor: SIGA Technologies

Brief Summary

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.

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 Timeline

• Study First Submitted: 2009-05-21
• Study First Submitted QC: 2009-05-22
• Study First Posted: 2009-05-25
• Study Start: 2009-06
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Results First Submitted: 2010-07-29
• Results First Submitted QC: 2010-07-29
• Results First Posted: 2010-08-27
• Status Verified: 2010-09
• Last Update Submitted: 2010-09-15
• Last Update Posted: 2010-09-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ST-246 400 mg	ST-246 400 mg	ST-246 400mg (2 x 200 mg Capsules) Orally Once Daily for 14 days
ST-246 600 mg	ST-246 600 mg	ST-246 600 mg (3 x 200 mg Capsules) Orally Once Daily for 14 days
Placebo	Placebo	Matching Placebo capsules, Orally Once Daily for 14 days

Primary Outcome Measures

Name	Time	Method
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.	Days 1 to 14; then 24, 48, 72, 96 and 120 hours and 4 weeks after final dose	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

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

Trial Locations

Locations (3)

Hawaii Clinical Research Center; 🇺🇸 Honolulu, Hawaii, United States

Apex Research Institute; 🇺🇸 Santa Ana, California, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States