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| ID | Type | Description | Link |
|---|---|---|---|
| DMID 08-0055 | Other Identifier | NIH Contract: HHSN261002600014C |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ST-246 400 mg | Experimental | ST-246 400mg (2 x 200 mg Capsules) Orally Once Daily for 14 days |
|
| ST-246 600 mg | Experimental | ST-246 600 mg (3 x 200 mg Capsules) Orally Once Daily for 14 days |
|
| Placebo | Placebo Comparator | Matching Placebo capsules, Orally Once Daily for 14 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ST-246 400 mg | Drug | Capsules, 400 mg daily for 14 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Study Participants Who Tolerated a Single Daily Oral ST-246 Dose as Determined by Safety Parameter Changes According to the DAIDS (Division of Acquired Immunodeficiency Syndrome) Adverse Events (AE) Grading Table. | Subjects were administered a single, daily oral dose of ST-246 (400 or 600 mg)and changes in safety parameteres were monitored. Safety parameters included adverse events, vital signs, physical examinations, laboratory tests (hematology, blood chemistry, and urinalysis) and electrocardiograms. The DAIDS AE grading table is a list of common terms and severity (intensity) of parameters used to describe adverse events occurring in NIAID-sponsored clinical studies/trials. | Days 1 to 14; then 24, 48, 72, 96 and 120 hours and 4 weeks after final dose |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax | Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data | Day 1 post-dose |
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Marbury, MD | Orlando Clinical Research Center | Principal Investigator |
| Erik Ross, MD | Apex Research Institute | Principal Investigator |
| Jon Ruckle, MD | Hawaii Clinical Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Apex Research Institute | Santa Ana | California | 92705 | United States | ||
| Orlando Clinical Research Center |
Following an up to 14-day Screening Period, eligible subjects were randomly assigned to receive either ST-246 400 mg (n=45) or ST-246 600 mg (n=46) or placebo (n=16). Treatment was orally administered after a light meal over a 14-day Treatment Period. There was a 28-day Follow-up Period.
This study was conducted at three sites: Apex Research Institute, Santa Ana, CA, Hawaii Clinical Research Center, Honolulu, HI, and Orlando Clinical Research Center, Orlando, FL. The study was conducted in male and female volunteers ages 18 - 75 years inclusive from the sites' databases.
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| ID | Title | Description |
|---|---|---|
| FG000 | ST-246 400 mg | 400 mg ST-246 (2 x 200 mg capsules) given as a single daily oral dose to 45 subjects for 14 days. |
| FG001 | ST-246 600 mg | 600 mg ST-246 (3 x 200 mg capsules) given as a single daily oral dose to 46 subjects for 14 days. |
| FG002 | Placebo | Matching Placebo capsules given as a single daily oral dose to 16 subjects for 14 days. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ST-246 400 mg | 400 mg ST-246 (2 x 200 mg capsules) given as a single daily oral dose to 45 subjects for 14 days. |
| BG001 | ST-246 600 mg | 600 mg ST-246 (3 x 200 mg capsules) given as a single daily oral dose to 46 subjects for 14 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Study Participants Who Tolerated a Single Daily Oral ST-246 Dose as Determined by Safety Parameter Changes According to the DAIDS (Division of Acquired Immunodeficiency Syndrome) Adverse Events (AE) Grading Table. | Subjects were administered a single, daily oral dose of ST-246 (400 or 600 mg)and changes in safety parameteres were monitored. Safety parameters included adverse events, vital signs, physical examinations, laboratory tests (hematology, blood chemistry, and urinalysis) and electrocardiograms. The DAIDS AE grading table is a list of common terms and severity (intensity) of parameters used to describe adverse events occurring in NIAID-sponsored clinical studies/trials. | As per protocol. During the study, a total of 6 withdrawals occurred. These were due to adverse events (2) and consent withdrawal (1) in the 400 mg group, and subject request (1), lost to follow-up (1) and protocol violation (1) in the 600 mg group. | Posted | Number | Participants | Days 1 to 14; then 24, 48, 72, 96 and 120 hours and 4 weeks after final dose |
|
6 weeks
Study drug was administered once a day to each dosing group for 14 days, and subjects were followed for an additional 28 days. AEs were recorded throughout this time period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ST-246 400 mg | 400 mg ST-246 (2 x 200 mg capsules) given as a single daily oral dose to 45 subjects for 14 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Annie Frimm, Vice President, Regulatory Affairs | SIGA Technologies, Inc. | 951-303-8797 | afrimm@siga.com |
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| ID | Term |
|---|---|
| D012899 | Smallpox |
| ID | Term |
|---|---|
| D011213 | Poxviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C505045 | tecovirimat |
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| ST-246 600 mg | Drug | Capsules, 600 mg daily for 14 days |
|
|
| Placebo | Drug | Capsules, once daily for 14 days |
|
Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data |
| Day 14 post-dose |
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax | Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles | Day 1 post-dose |
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax | Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles | Day 14 post-dose |
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau | AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule | Day 1 post-dose |
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau | AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule | Day 14 post-dose |
| Evaluation of Pharmacokinetic Parameters to Assess Interventions: t½ | t½: Observed terminal elimination half-life determined after the last dose on Day 14 | Day 14 post-dose |
| Orlando |
| Florida |
| 32809 |
| United States |
| Hawaii Clinical Research Center | Honolulu | Hawaii | 96813 | United States |
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
| Protocol Violation |
|
| BG002 | Placebo | Matching Placebo capsules given as a single daily oral dose to 16 subjects for 14 days. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 |
| ST-246 400 mg |
400 mg ST-246 (2 x 200 mg capsules) given as a single daily oral dose to 45 subjects for 14 days. |
| OG001 | ST-246 600 mg | 600 mg ST-246 (3 x 200 mg capsules) given as a single daily oral dose to 46 subjects for 14 days. |
| OG002 | Placebo | Matching Placebo capsules given as a single daily oral dose to 16 subjects for 14 days. |
|
|
| Secondary | Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax | Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data | As per protocol. All 16 subjects in the placebo group were excluded from the PK population. In addition, 2 subjects in each of the ST-246 400 mg and 600 mg groups were excluded due to early withdrawals. | Posted | Mean | Standard Deviation | ng/mL | Day 1 post-dose |
|
|
|
| Secondary | Evaluation of Pharmacokinetic Parameters to Assess Interventions: Cmax | Cmax: Maximum drug concentration in plasma determined directly from individual concentration-time data | As per protocol. All 16 subjects in the placebo group were excluded from the PK population. In addition, 4 subjects in each of the ST-246 400 mg and 600 mg groups were excluded from PK analysis due to withdrawals or because PK data fell below the limit of quantitation (BLQ). | Posted | Mean | Standard Deviation | ng/mL | Day 14 post-dose |
|
|
|
| Secondary | Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax | Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles | As per protocol. All 16 subjects in the placebo group were excluded from the PK population. In addition, 2 subjects in each of the ST-246 400 mg and 600 mg groups were excluded due to early withdrawals. | Posted | Mean | Standard Deviation | hours | Day 1 post-dose |
|
|
|
| Secondary | Evaluation of Pharmacokinetic Parameters to Assess Interventions: Tmax | Tmax: Time to reach maximum drug concentration in plasma calculated from [plasma] versus time profiles | As per protocol. All 16 subjects in the placebo group were excluded from the PK population. In addition, 4 and 5 subjects in the ST-246 400 mg and 600 mg groups respectively, were excluded from PK analysis due to withdrawals or because PK data fell below the limit of quantitation (BLQ). | Posted | Mean | Standard Deviation | hours | Day 14 post-dose |
|
|
|
| Secondary | Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau | AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule | As per protocol. All 16 subjects in the placebo group were excluded from the PK population. In addition, 23 subjects in each of the ST-246 400 mg and 600 mg groups were excluded from PK analysis due to early withdrawals or because PK data fell below the limit of quantitation (BLQ) before the 24-hour dosing interval was complete. | Posted | Mean | Standard Deviation | ng*hr/mL | Day 1 post-dose |
|
|
|
| Secondary | Evaluation of Pharmacokinetic Parameters to Assess Interventions: AUCtau | AUCtau: Area under the plasma concentration-time curve for each dosing interval (from time 0 to 24 hours sample) determined using the linear trapezoidal rule | As per protocol. All 16 subjects in the placebo group were excluded from the PK population. In addition, 5 and 6 subjects in the ST-246 400 mg and 600 mg groups respectively, were excluded from PK analysis due to withdrawals or because PK data fell below the limit of quantitation (BLQ). | Posted | Mean | Standard Deviation | ng*hr/mL | Day 14 post-dose |
|
|
|
| Secondary | Evaluation of Pharmacokinetic Parameters to Assess Interventions: t½ | t½: Observed terminal elimination half-life determined after the last dose on Day 14 | As per protocol. All 16 subjects in the placebo group were excluded from the PK population. In addition, 21 and 20 subjects in the ST-246 400 mg and 600 mg groups respectively, were excluded from PK analysis due to early withdrawals or because PK data fell below the limit of quantitation (BLQ). | Posted | Mean | Standard Deviation | hours | Day 14 post-dose |
|
|
|
| 0 |
| 45 |
| 11 |
| 45 |
| EG001 | ST-246 600 mg | 600 mg ST-246 (3 x 200 mg capsules) given as a single daily oral dose to 46 subjects for 14 days. | 0 | 46 | 8 | 46 |
| EG002 | Placebo | Matching Placebo capsules given as a single daily oral dose to 16 subjects for 14 days. | 0 | 16 | 1 | 16 |
| Axillary pain | General disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Neutropenia | Investigations | MedDRA (10.0) | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Tension headache | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
|
The PI must obtain the sponsor's written consent to publish any study results and must notify the sponsor within 30 working days prior to publishing.