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

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.

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.

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