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 Normal Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- ST-246 Days 1 - 3
- Conditions
- Orthopoxviral Disease
- Sponsor
- SIGA Technologies
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: t½
- Status
- Completed
- Last Updated
- 10 years ago
Overview
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 Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •18 to 50 years
- •Available for clinical follow-up duration of study.
- •Able/willing to give written consent.
- •Good general health; no clinically significant medical history.
- •Refrain from taking any medications from screening through 72 hours after last dose.
- •Adequate venous access.
- •PE and lab results without clinically significant findings within 28 days prior to receipt of drug.
- •Meet Lab Criteria within 28 days prior to receipt of drug.
- •Negative pregnancy test
- •Non smokers
Exclusion Criteria
- •Marked baseline prolongation of QT/corrected QT interval (QTc) interval (
- •History of additional risk factors for Torsade de Pointes
- •Clinically significant abnormal ECG
- •Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or prolongation of the PR interval
- •Family history of Sudden Cardiac Death not clearly due to acute myocardial infarction.
- •History of any clinically significant conditions including:
- •Diabetes mellitus
- •History of thyroidectomy or thyroid disease
- •Serious angioedema episodes
- •Head trauma resulting in a diagnosis of TBI other than concussion
Arms & Interventions
Group ST-246 Form I (followed by Form V)
Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
Intervention: ST-246 Days 1 - 3
Group ST-246 Form I (followed by Form V)
Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
Intervention: ST-246 Days 11 - 13
Group ST-246 Form V (followed by Form I)
Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
Intervention: ST-246 Days 1 - 3
Group ST-246 Form V (followed by Form I)
Each of six subjects receive a single oral 400 mg dose (2×200 mg) of ST-246 Form V (hemihydrate) in the first intervention period, followed 10 days later (3 days post-treatment monitoring and 7 days wash-out period) in the second intervention period by a single oral 400 mg dose (2×200 mg) of ST-246 Form I (monohydrate). Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
Intervention: ST-246 Days 11 - 13
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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(4 weeks)