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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000793-60 | EudraCT Number |
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The purpose of this study is to evaluate the safety and pharmacokinetic profile of single and multiple ascending intravenous doses of 3K3A-APC in healthy adult subjects aged 18-55 years.
This is a single-center, sequential-cohort, double-blind, placebo-controlled, single- and multiple-ascending dose study. Eligible adult subjects will be assigned sequentially to 1 of 10 cohorts, at successively higher single doses, followed by successively higher multiple doses.
Single IV Doses: 5 subjects per cohort, aged 18-55, will be randomized in a 4:1 manner to receive active drug (6, 30, 90, 180, 360, and TBD µg/kg) or to receive matching placebo (Cohorts 1-6).
Multiple IV Doses: 8 subjects per cohort, aged 18-55, will be randomized in a 3:1 manner to receive active drug (90, 180, 360, and TBD µg/kg) or to receive matching placebo every 12 hours for 5 doses (Cohorts 7-10).
Single-Dose Cohorts Subjects receiving a single dose will be confined in a Phase 1 unit for 12 hours prior to dosing, during dosing, and for 24 hours after dosing (Study Day 1-2) for observation and PK sampling. Subjects will return on Study Day 4 (~72 hours after infusion) and Study Day 15 for additional safety evaluations. A 28-Day follow-up phone call will be made to subjects to collect AEs that occur within 28-days of the dose.
Multiple-Dose Cohorts Subjects receiving multiple doses will be confined in a Phase 1 unit for 12 hours prior to dosing through 24 hours following the last dose (Study Day 1-4) for observation and PK sampling. Subjects will return on Study Day 6 (~72 hours after last infusion) and Study Day 15 for additional safety evaluations. A 28-Day follow-up phone call will be made to subjects to collect AEs that occur within 28-days of the last dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 6 µg/kg 3K3A-APC, single-dose | Active Comparator | Cohort 1: 6 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 20 mL IV infusion over 15 minutes |
|
| 30 µg/kg 3K3A-APC, single-dose | Active Comparator | Cohort 2: 30 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes |
|
| 90 µg/kg 3K3A-APC, single-dose | Active Comparator | Cohort 3: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes |
|
| 180 µg/kg 3K3A-APC, single-dose | Active Comparator | Cohort 4: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes |
|
| 360 µg/kg 3K3A-APC, single-dose | Active Comparator | Cohort 5: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3K3A-APC, diluted in 0.9% sodium chloride in water | Biological |
|
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in Protocol. | Day 4 for single-dose cohorts | |
| Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in the Protocol. | Day 6 for multiple-dose cohorts |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Time at Which Cmax is Observed (Tmax) for 3K3A-APC by Non-compartmental Analysis |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick D Lyden, MD, FAAN | Cedars-Sinai Medical Center | Principal Investigator |
| Howard Levy, MD, PhD, MMM | ZZ Biotech, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Privatklinik Leech | Graz | 8010 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24372304 | Derived | Lyden P, Levy H, Weymer S, Pryor K, Kramer W, Griffin JH, Davis TP, Zlokovic B. Phase 1 safety, tolerability and pharmacokinetics of 3K3A-APC in healthy adult volunteers. Curr Pharm Des. 2013;19(42):7479-85. doi: 10.2174/1381612819666131230131454. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 6 µg/kg 3K3A-APC, Single-dose | Cohort 1: 6 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 20 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG001 | 30 µg/kg 3K3A-APC, Single-dose | Cohort 2: 30 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG002 | 90 µg/kg 3K3A-APC, Single-dose | Cohort 3: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG003 | 180 µg/kg 3K3A-APC, Single-dose | Cohort 4: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG004 | 360 µg/kg 3K3A-APC, Single-dose | Cohort 5: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG005 | 720 µg/kg 3K3A-APC, Single-dose | Cohort 6: TBD (not to exceed 720) 720 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG006 | 540 µg/kg 3K3A-APC, Single-dose | Cohort 6: TBD (not to exceed 720) 540 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG007 | 90 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 7: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG008 | 180 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 8: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG009 | 360 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 9: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG010 | 540 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 10: 540 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water |
| FG011 | Matching Placebo, 0.9% NaCl in Water | Cohorts 1-10: 0.9% sodium chloride in water and administered as either 20 mL IV infusion over 15 minutes (Cohort 1), or 100 mL IV infusion over 15 minutes (Cohorts 2-10) 0.9% NaCl in water |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 6 µg/kg 3K3A-APC, Single-dose | Cohort 1: 6 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 20 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG001 | 30 µg/kg 3K3A-APC, Single-dose |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in Protocol. | All 'single-dose' subjects who received at least one dose of study treatment. | Posted | Number | participants | Day 4 for single-dose cohorts |
|
AEs were reported from the first dose of study drug through 28 Days following the last dose (Day 28 Follow-up visit).
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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 | 6 µg/kg 3K3A-APC, Single-dose | Cohort 1: 6 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 20 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
Samples were analyzed from 4 treated subjects in the 6 μg/kg dose group, but all values were below the lower limit of quantitation for the assay (75 ng/mL) and therefore no PK analysis could be performed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kent Pryor, PhD, MBA, Chief Operating Officer | ZZ Biotech, LLC | kpryor@zzbiotech.com |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| D014867 | Water |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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|
| TBD µg/kg 3K3A-APC, single-dose | Active Comparator | Cohort 6: TBD (not to exceed 720) µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes |
|
| 90 µg/kg 3K3A-APC, q12h for 5 doses | Active Comparator | Cohort 7: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses |
|
| 180 µg/kg 3K3A-APC, q12h for 5 doses | Active Comparator | Cohort 8: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses |
|
| 360 µg/kg 3K3A-APC, q12h for 5 doses | Active Comparator | Cohort 9: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses |
|
| TBD µg/kg 3K3A-APC, q12h for 5 doses | Active Comparator | Cohort 10: TBD (not to exceed 720) µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses |
|
| Matching Placebo, 0.9% NaCl in water | Placebo Comparator | Cohorts 1-10: 0.9% sodium chloride in water and administered as either 20 mL IV infusion over 15 minutes (Cohort 1), or 100 mL IV infusion over 15 minutes (Cohorts 2-10) |
|
| 0.9% NaCl in water | Drug |
|
Single-dose cohorts |
| 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time 0 to the Final Time With a Concentration ≥ Limit of Quantitation [AUC(0-t)] for 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-inf)] for 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Elimination Rate Constant (λz) for 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Half-life (t1/2) of 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Total Clearance (CL) of 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Volume of Distribution (Vz) of 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Compartmental Analysis | Single-dose cohorts | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-inf)] for 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Elimination Rate Constant (λz) for 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Half-life (t1/2) of 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Total Clearance (CL) of 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Volume of Distribution (V) of 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 20 minutes and 1 hour post for doses 1 and 5 |
| Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-inf)] for 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 20 minutes and 1 hour post for doses 1 and 5 |
| Elimination Rate Constant (λz) for 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 20 minutes and 1 hour post for doses 1 and 5 |
| Half-life (t1/2) of 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 20 minutes and 1 hour post for doses 1 and 5 |
| Total Clearance (CL) of 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 20 minutes and 1 hour post for doses 1 and 5 |
| Volume of Distribution (V) of 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | 0, 20 minutes and 1 hour post for doses 1 and 5 |
Cohort 2: 30 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG002 | 90 µg/kg 3K3A-APC, Single-dose | Cohort 3: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG003 | 180 µg/kg 3K3A-APC, Single-dose | Cohort 4: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG004 | 360 µg/kg 3K3A-APC, Single-dose | Cohort 5: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG005 | 720 µg/kg 3K3A-APC, Single-dose | Cohort 6: TBD (not to exceed 720) 720 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG006 | 540 µg/kg 3K3A-APC, Single-dose | Cohort 6: TBD (not to exceed 720) 540 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG007 | 90 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 7: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG008 | 180 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 8: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG009 | 360 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 9: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG010 | 540 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 10: 540 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water |
| BG011 | Matching Placebo, 0.9% NaCl in Water | Cohorts 1-10: 0.9% sodium chloride in water and administered as either 20 mL IV infusion over 15 minutes (Cohort 1), or 100 mL IV infusion over 15 minutes (Cohorts 2-10) 0.9% NaCl in water |
| BG012 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | 90 µg/kg 3K3A-APC, Single-dose | Cohort 3: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| OG003 | 180 µg/kg 3K3A-APC, Single-dose | Cohort 4: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| OG004 | 360 µg/kg 3K3A-APC, Single-dose | Cohort 5: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| OG005 | 720 µg/kg 3K3A-APC, Single-dose | Cohort 6: TBD (not to exceed 720) 720 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| OG006 | 540 µg/kg 3K3A-APC, Single-dose | Cohort 6: TBD (not to exceed 720) 540 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water |
| OG007 | Matching Placebo, 0.9% NaCl in Water | Cohorts 1-10: 0.9% sodium chloride in water and administered as either 20 mL IV infusion over 15 minutes (Cohort 1), or 100 mL IV infusion over 15 minutes (Cohorts 2-10) 0.9% NaCl in water |
|
|
| Primary | Adverse Events That Meet Dose-limiting Toxicity Criteria Specified in the Protocol. | All 'multiple-dose' subjects who received at least one dose of study treatment. | Posted | Number | participants | Day 6 for multiple-dose cohorts |
|
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | ng/mL | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
|
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| Secondary | Time at Which Cmax is Observed (Tmax) for 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Median | Full Range | hour (from start of infusion) | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
|
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| Secondary | Area Under the Plasma Concentration-time Curve From Time 0 to the Final Time With a Concentration ≥ Limit of Quantitation [AUC(0-t)] for 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | h * ng/mL | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
|
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| Secondary | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-inf)] for 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | h * ng/mL | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
|
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| Secondary | Elimination Rate Constant (λz) for 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | L/h | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
|
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| Secondary | Half-life (t1/2) of 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | h | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
|
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| Secondary | Total Clearance (CL) of 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | mL/h | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
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| Secondary | Volume of Distribution (Vz) of 3K3A-APC by Non-compartmental Analysis | Single-dose cohorts | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | mL | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Compartmental Analysis | Single-dose cohorts | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | ng/mL | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
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| Secondary | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-inf)] for 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | h * ng/mL | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
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| Secondary | Elimination Rate Constant (λz) for 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | L/h | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
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| Secondary | Half-life (t1/2) of 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | h | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
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| Secondary | Total Clearance (CL) of 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | mL/h | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
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| Secondary | Volume of Distribution (V) of 3K3A-APC by Compartmental Analysis | Single-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'single-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | mL | 0, 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'multiple-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | ng/mL | 0, 20 minutes and 1 hour post for doses 1 and 5 |
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| Secondary | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-inf)] for 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'multiple-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | h * ng/mL | 0, 20 minutes and 1 hour post for doses 1 and 5 |
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| Secondary | Elimination Rate Constant (λz) for 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'multiple-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | L/h | 0, 20 minutes and 1 hour post for doses 1 and 5 |
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| Secondary | Half-life (t1/2) of 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'multiple-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | h | 0, 20 minutes and 1 hour post for doses 1 and 5 |
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| Secondary | Total Clearance (CL) of 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'multiple-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | mL/h | 0, 20 minutes and 1 hour post for doses 1 and 5 |
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| Secondary | Volume of Distribution (V) of 3K3A-APC by Compartmental Analysis | Multiple-dose cohorts; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | All 'multiple-dose' subjects who received at least one dose of study treatment and who have sufficient data for PK analysis and who have not been excluded from analysis for protocol deviations or other study-related events that could impact the calculation or interpretation of the pharmacokinetic parameters. | Posted | Mean | Standard Deviation | mL | 0, 20 minutes and 1 hour post for doses 1 and 5 |
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| 0 |
| 4 |
| 0 |
| 4 |
| EG001 | 30 µg/kg 3K3A-APC, Single-dose | Cohort 2: 30 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 4 | 2 | 4 |
| EG002 | 90 µg/kg 3K3A-APC, Single-dose | Cohort 3: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 4 | 0 | 4 |
| EG003 | 180 µg/kg 3K3A-APC, Single-dose | Cohort 4: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 4 | 1 | 4 |
| EG004 | 360 µg/kg 3K3A-APC, Single-dose | Cohort 5: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 4 | 3 | 4 |
| EG005 | 720 µg/kg 3K3A-APC, Single-dose | Cohort 6: TBD (not to exceed 720) 720 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 2 | 2 | 2 |
| EG006 | 540 µg/kg 3K3A-APC, Single-dose | Cohort 6: TBD (not to exceed 720) 540 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 4 | 4 | 4 |
| EG007 | 90 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 7: 90 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 6 | 5 | 6 |
| EG008 | 180 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 8: 180 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 6 | 2 | 6 |
| EG009 | 360 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 9: 360 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 6 | 6 | 6 |
| EG010 | 540 µg/kg 3K3A-APC, q12h for 5 Doses | Cohort 10: 540 µg/kg 3K3A-APC, diluted in 0.9% sodium chloride in water and administered as an 100 mL IV infusion over 15 minutes; given every 12 hours for 5 doses 3K3A-APC, diluted in 0.9% sodium chloride in water | 0 | 6 | 5 | 6 |
| EG011 | Matching Placebo, 0.9% NaCl in Water | Cohorts 1-10: 0.9% sodium chloride in water and administered as either 20 mL IV infusion over 15 minutes (Cohort 1), or 100 mL IV infusion over 15 minutes (Cohorts 2-10) 0.9% NaCl in water | 0 | 14 | 6 | 14 |
| Syncope | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
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| Vertigo | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
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| Migraine | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Gingivitis | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Hyperhidrosis | General disorders | MedDRA (12.0) | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
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| Sinus Bradycardia | Cardiac disorders | MedDRA (12.0) | Systematic Assessment |
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| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
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Not provided
| D017670 |
| Sodium Compounds |
| D006878 | Hydroxides |
| D000468 | Alkalies |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |