Trial Outcomes & Findings for Phase I Trial of an Investigational Small Pox Medication (NCT NCT00728689)
NCT ID: NCT00728689
Last Updated: 2015-06-29
Results Overview
Mean terminal half-life (t½; hrs) for Forms I and V were calculated from \[plasma\] vs time profiles.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrs
Results posted on
2015-06-29
Participant Flow
Study period was approximately 2 weeks (from August 26, 2008 to September 8, 2008), plus a 30-day post-treatment follow up. The study was conducted at a Phase I Study Unit of a Clinical Research Center in Orlando, FL.
All participants needed to meet strict entry criteria. Sixty-three subjects were screened to randomize 12 subjects into the study.
Participant milestones
| Measure |
ST-246 Form I Followed by Form V
Each of six subjects receive a single 400 mg dose (2×200 mg) of ST-246 Form I, followed 10 days later by a single 400 mg dose (2×200 mg) of ST-246 Form V. Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
ST-246 Form V Followed by Form I
Each of six subjects receive a single 400 mg dose (2×200 mg) of ST-246 Form V, followed 10 days later by a single 400 mg dose (2×200 mg) of ST-246 Form I. Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
|---|---|---|
|
First Intervention (Days 1 - 3)
STARTED
|
6
|
6
|
|
First Intervention (Days 1 - 3)
COMPLETED
|
6
|
6
|
|
First Intervention (Days 1 - 3)
NOT COMPLETED
|
0
|
0
|
|
Washout Period (Days 4 - 10)
STARTED
|
6
|
6
|
|
Washout Period (Days 4 - 10)
COMPLETED
|
5
|
6
|
|
Washout Period (Days 4 - 10)
NOT COMPLETED
|
1
|
0
|
|
Second Intervention (Days 11 - 13)
STARTED
|
5
|
6
|
|
Second Intervention (Days 11 - 13)
COMPLETED
|
5
|
6
|
|
Second Intervention (Days 11 - 13)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
ST-246 Form I Followed by Form V
Each of six subjects receive a single 400 mg dose (2×200 mg) of ST-246 Form I, followed 10 days later by a single 400 mg dose (2×200 mg) of ST-246 Form V. Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
ST-246 Form V Followed by Form I
Each of six subjects receive a single 400 mg dose (2×200 mg) of ST-246 Form V, followed 10 days later by a single 400 mg dose (2×200 mg) of ST-246 Form I. Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
|---|---|---|
|
Washout Period (Days 4 - 10)
Death in family
|
1
|
0
|
Baseline Characteristics
Phase I Trial of an Investigational Small Pox Medication
Baseline characteristics by cohort
| Measure |
ST-246 Form I Followed by Form V
n=6 Participants
Each of six subjects receive a single 400 mg dose (2×200 mg) of ST-246 Form I, followed 10 days later by a single 400 mg dose (2×200 mg) of ST-246 Form V. Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
ST-246 Form V Followed by Form I
n=6 Participants
Each of six subjects receive a single 400 mg dose (2×200 mg) of ST-246 Form V, followed 10 days later by a single 400 mg dose (2×200 mg) of ST-246 Form I. Both forms of drug are orally administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
34.7 years
STANDARD_DEVIATION 8 • n=99 Participants
|
34.8 years
STANDARD_DEVIATION 9.4 • n=107 Participants
|
34.8 years
STANDARD_DEVIATION 8.3 • n=206 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=99 Participants
|
6 participants
n=107 Participants
|
12 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrsPopulation: Both groups started with 12 particpants. Outlier values were excluded from the half-life analyses for 3 subject PK profiles (one Form I and 2 Form V). Form V group lost a particpant during wash-out period due to death in the family.
Mean terminal half-life (t½; hrs) for Forms I and V were calculated from \[plasma\] vs time profiles.
Outcome measures
| Measure |
ST-246 Form I
n=11 Participants
ST-246 Form I administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
ST-246 Form V
n=8 Participants
ST-246 Form V administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
|---|---|---|
|
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: t½
|
27.446 hours
Standard Deviation 13.109
|
28.180 hours
Standard Deviation 21.992
|
PRIMARY outcome
Timeframe: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrsPopulation: Both groups started with 12 particpants. Form V group lost a particpant during wash-out period due to death in the family.
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).
Outcome measures
| Measure |
ST-246 Form I
n=12 Participants
ST-246 Form I administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
ST-246 Form V
n=11 Participants
ST-246 Form V administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
|---|---|---|
|
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-τ
|
15624.495 ng*hr/mL
Standard Deviation 5449.188
|
20065.316 ng*hr/mL
Standard Deviation 6744.974
|
PRIMARY outcome
Timeframe: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrsPopulation: Both groups started with 12 particpants. Outlier values were excluded from analyses for 3 subject PK profiles (one Form I and 2 Form V). Form V group lost a particpant during wash-out period due to death in the family.
Area under the drug concentration-time curve from time zero to infinity (AUC0-∞; ng\*hr/mL).
Outcome measures
| Measure |
ST-246 Form I
n=11 Participants
ST-246 Form I administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
ST-246 Form V
n=8 Participants
ST-246 Form V administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
|---|---|---|
|
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: AUC0-∞
|
19922.017 ng*hr/mL
Standard Deviation 6543.563
|
21982.709 ng*hr/mL
Standard Deviation 9330.953
|
PRIMARY outcome
Timeframe: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrsPopulation: Both groups started with 12 particpants as 'per protocol'. Form V group lost a particpant during wash-out period due to death in the family.
Maximum drug concentration in plasma, determined directly from individual concentration-time data (Cmax)
Outcome measures
| Measure |
ST-246 Form I
n=12 Participants
ST-246 Form I administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
ST-246 Form V
n=11 Participants
ST-246 Form V administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
|---|---|---|
|
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Cmax
|
1068.9 ng/mL
Standard Deviation 294.3
|
1230.2 ng/mL
Standard Deviation 348.6
|
PRIMARY outcome
Timeframe: Post-dose samples at 0.5,1,2,3,4,8,12,24,36,48,72 hrsPopulation: Both groups started with 12 particpants. Form V group lost a particpant during wash-out period due to death in the family.
Time to maximum plasma concentration(Tmax; hrs) for Forms I and V were calculated from \[plasma\] vs time profiles.
Outcome measures
| Measure |
ST-246 Form I
n=12 Participants
ST-246 Form I administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
ST-246 Form V
n=11 Participants
ST-246 Form V administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
|---|---|---|
|
Pharmacokinetic Parameters for a Single Dose of ST-246 Form I vs. Form V: Tmax
|
3.8 hours
Standard Deviation 1.5
|
3.8 hours
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Both groups started with 12 particpants. Form V group lost a particpant during wash-out period due to death in the family.
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.
Outcome measures
| Measure |
ST-246 Form I
n=12 Participants
ST-246 Form I administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
ST-246 Form V
n=11 Participants
ST-246 Form V administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period. Drug was administered within 30 minutes after a standard light meal consisting of 400-450 calories and approximately 25% fat.
|
|---|---|---|
|
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
|
12 participants
|
11 participants
|
Adverse Events
ST-246 Form I
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
ST-246 Form V
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
ST-246 Form I
n=12 participants at risk
ST-246 Form I administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period.
|
ST-246 Form V
n=11 participants at risk
ST-246 Form V administered as a single 400 mg oral dose (2×200 mg) in either first intervention period or second intervention period.
|
|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/12 • 4 weeks
Twelve subjects received Form I once and 11 of the same 12 subjects received Form V once. AEs and SAEs were recorded until 72 hours and 30 days, respectively, after administration of final dose of study drug. Recording at Day 41± 2 was via phone contact. Unsolicited AEs were recorded at anytime including during the 10-day washout period.
|
9.1%
1/11 • Number of events 1 • 4 weeks
Twelve subjects received Form I once and 11 of the same 12 subjects received Form V once. AEs and SAEs were recorded until 72 hours and 30 days, respectively, after administration of final dose of study drug. Recording at Day 41± 2 was via phone contact. Unsolicited AEs were recorded at anytime including during the 10-day washout period.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/12 • 4 weeks
Twelve subjects received Form I once and 11 of the same 12 subjects received Form V once. AEs and SAEs were recorded until 72 hours and 30 days, respectively, after administration of final dose of study drug. Recording at Day 41± 2 was via phone contact. Unsolicited AEs were recorded at anytime including during the 10-day washout period.
|
9.1%
1/11 • Number of events 2 • 4 weeks
Twelve subjects received Form I once and 11 of the same 12 subjects received Form V once. AEs and SAEs were recorded until 72 hours and 30 days, respectively, after administration of final dose of study drug. Recording at Day 41± 2 was via phone contact. Unsolicited AEs were recorded at anytime including during the 10-day washout period.
|
|
General disorders
Underarm tenderness
|
8.3%
1/12 • Number of events 1 • 4 weeks
Twelve subjects received Form I once and 11 of the same 12 subjects received Form V once. AEs and SAEs were recorded until 72 hours and 30 days, respectively, after administration of final dose of study drug. Recording at Day 41± 2 was via phone contact. Unsolicited AEs were recorded at anytime including during the 10-day washout period.
|
0.00%
0/11 • 4 weeks
Twelve subjects received Form I once and 11 of the same 12 subjects received Form V once. AEs and SAEs were recorded until 72 hours and 30 days, respectively, after administration of final dose of study drug. Recording at Day 41± 2 was via phone contact. Unsolicited AEs were recorded at anytime including during the 10-day washout period.
|
Additional Information
Annie Frimm, Vice President, Regulatory Affairs
Siga Technologies, Inc.
Phone: 951-303-8797
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee PI must have sponsor's written consent to publish and must provide information to the sponsor at least 30 working days prior to publication submission deadline.
- Publication restrictions are in place
Restriction type: OTHER