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
Overview
- Phase
- Phase 2
- Intervention
- ST-246 400 mg
- Conditions
- Orthopoxviral Disease
- Sponsor
- SIGA Technologies
- Enrollment
- 107
- Locations
- 3
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 15 years ago
Overview
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.
Investigators
Eligibility 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
Arms & Interventions
ST-246 400 mg
ST-246 400mg (2 x 200 mg Capsules) Orally Once Daily for 14 days
Intervention: ST-246 400 mg
ST-246 600 mg
ST-246 600 mg (3 x 200 mg Capsules) Orally Once Daily for 14 days
Intervention: ST-246 600 mg
Placebo
Matching Placebo capsules, Orally Once Daily for 14 days
Intervention: Placebo
Outcomes
Primary Outcomes
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
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 Outcomes
- Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax(Day 14 post-dose)
- Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax(Day 14 post-dose)
- Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau(Day 14 post-dose)
- Evaluation of Pharmacokinetic Parameters to Assess Interventions: t½(Day 14 post-dose)