Clinical Trial: Phase I Trial of an Investigational Small Pox Medication

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Randomized, Double-Blind, Crossover, Exploratory Study of the Pharmacokinetics of a Single Oral Dose of Form I Versus Form V Capsules of the Anti-Orthopoxvirus Compound ST-246® in Fed N

Brief Summary: The purpose of this study was to evaluate the pharmacokinetic parameters and safety of a single dose of ST-246 400mg Form I versus ST-246 400mg Form V capsules in fed normal healthy volunteers.

Detailed Summary:

This was a Phase I, double-blind, cross-over, single-dose study of the orally administered anti-orthopoxvirus compound, ST-246, to 12 healthy, fed volunteers between the ages of 18 and 50 years. Subjects were randomized such that 6 subjects received either ST-246 Form I (monohydrate) followed 10 days later after a wash-out period by Form V (hemihydrate), and 6 subjects received ST-246 Form V followed by Form I, as for the previous group.

Both forms of ST-246 were similar in the way they were manufactured. The only difference between Form I and Form V may be related to how it dissolves, and this may affect the way that it is absorbed in the human body. Information about any side-effects that may occur will also be collected in this study.


Sponsor: SIGA Technologies

Current Primary Outcome:

  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: t½ [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ]
    Mean terminal half-life (t½; hrs) for Forms I and V were calculated from [plasma] vs time profiles.
  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-τ [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ]
    Area under the drug concentration-time curve from time zero to time t, where t is the last timepoint with a drug concentration ≥ lowest obtainable quantification (AUC0-τ; ng*hr/mL).
  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-∞ [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ]
    Area under the drug concentration-time curve from time zero to infinity (AUC0-∞; ng*hr/mL).
  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Cmax [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ]
    Maximum drug concentration in plasma, determined directly from individual concentration-time data (Cmax)
  • Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Tmax [ Time Frame: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs ]
    Time to maximum plasma concentration(Tmax; hrs) for Forms I and V were calculated from [plasma] vs time profiles.


Original Primary Outcome: The comparison of pharmacokinetic parameters of area under the curve (AUC) and Cmax of Form I and Form V of ST-246 400 mg (2 × 200 mg) in fed, healthy subjects as assessed through blood samples. [ Time Frame: 4 weeks ]

Current Secondary Outcome: Number of Study Participants Who Tolerated a Single Dose of ST-246 Form I vs. Form V as Determined by No Clinically Significant Changes in Safety Parameters [ Time Frame: 4 weeks ]

Evaluated safety parameters included:

  1. physical examination/vital signs
  2. electrocardiograms (heart rate, PR interval, QRS duration, QT interval, and QTc Bazett)
  3. laboratory safety tests (hematology, chemistry, urinalysis)
  4. adverse events For a), b) and c), summary statistics (mean,SD, median, minm, maxm)for values, and changes from baseline(Day 1 pre-dose) to each timepoint, were measured and compared to laboratory normal reference ranges. Values for a)- d) were assigned grades according to DAIDS AE Grading Table. Any Grade of 3 or higher was considered severe and significant.


Original Secondary Outcome: To evaluate the safety and tolerability of Form I and Form V of ST-246 in fed, normal, and healthy subjects as assessed through physical examination, vital signs, electrocardiograms (ECG), laboratory tests, and adverse events (AEs). [ Time Frame: 4 weeks ]

Information By: SIGA Technologies

Dates:
Date Received: August 1, 2008
Date Started: August 2008
Date Completion:
Last Updated: June 22, 2015
Last Verified: September 2010