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:
- physical examination/vital signs
- electrocardiograms (heart rate, PR interval, QRS duration, QT interval, and QTc Bazett)
- laboratory safety tests (hematology, chemistry, urinalysis)
- 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