Acute Peripheral Arterial Occlusion
Conditions
Keywords
Acute Limb Ischemia
Brief summary
The primary purpose of this Phase 2 study is to optimize Plasmin delivery by comparing different delivery regimens in patients with peripheral arterial occlusion. The study includes a blinded plasminogen activator treatment group and a blinded plasminogen activator placebo group. The study will also assess safety and tolerability of Plasmin at 150 and 250 mg doses.
Interventions
BIOLOGICALPlasmin
Plasmin prepared in 0.9% saline for injection
BIOLOGICALPlasminogen Activator
Plasminogen activator used according to the Investigator's clinical judgment.
OTHERPlacebo
Normal saline for injection at the same volume as the plasminogen activator.
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unilateral limb ischemia - Society of Vascular Surgery Categories I and IIa * Onset of symptoms less than or equal to 14 days * Thrombosed infrainguinal bypass graft or native artery * Diagnosis by arteriography of occlusive thrombus in graft or artery * Ability to embed the infusion catheter into the thrombus * Women of childbearing potential must use contraception and have a negative pregnancy test
Exclusion criteria
* Any medical or social condition that may interfere with study participation * Women who are pregnant or lactating * Hemorrhagic stroke history * Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack) within one year * Intracranial or spinal neurosurgery, or severe intracranial trauma in the last 3 months * Major surgery, organ biopsy, or major trauma within the past 10 days * Lumbar puncture or non-compressible arterial puncture in the past 10 days * Intraocular surgery within the past 10 days * Active gastrointestinal or organ bleeding * Uncontrolled arterial hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) * Known intracranial neoplasm, aneurysm, or arteriovenous malformation * Current bleeding diathesis * Platelet count \<75 x 10e9/L * Active graft infection * Occlusion occurred within one month of synthetic graft placement * Occlusion occurred within 6 months of autologous graft placement * A sequential composite graft with dual outflows to correct multiple occlusions * Medically unable to tolerate an open vascular procedure * Known prothrombotic state * Hemoglobin \<10.0 g/dL * Impaired renal function or renal disease that constitutes a contraindication to contrast angiography, including creatinine \>2.0 mg/dL * Treatment with a full dose plasminogen activator (PA) within the last 48 hours * Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within the past 5 days * Treatment with oral anticoagulants, and with an international normalized ratio of \>1.7
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects With >50% Thrombolysis | 5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J) | The proportion of subjects with \>50% thrombolysis at the end of treatment compared to baseline by arteriography. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | 30 days | The incidence of major and minor bleeding events, deaths, adverse events, serious adverse events, and abnormal laboratory values as a measure of safety and tolerability. |
Countries
Belgium, Bulgaria, Czechia, Germany, India, Peru, Poland, Romania, Serbia, Slovakia, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Plasmin Open-label Treatment Group A Open-label 150 mg Plasmin administered without initial proximal pulse; 5-hour infusion using 10 mL/hour infusion rate.
Plasmin: Plasmin prepared in 0.9% saline for injection | 20 |
| Plasmin Open-label Treatment Group B Open-label 150 mg Plasmin administered with initial proximal pulse; 5-hour infusion using 15 mL/hour infusion rate
Plasmin: Plasmin prepared in 0.9% saline for injection | 20 |
| Plasmin Open-label Treatment Group C Open-label 150 mg Plasmin administered with proximal pulse; 5 hour infusion using 30 mL/hour infusion rate.
Plasmin: Plasmin prepared in 0.9% saline for injection | 22 |
| Plasmin Open-label Treatment Group D Open-label 150 mg Plasmin administered with proximal pulse; 2-hour infusion using 35 mL/hour infusion rate
Plasmin: Plasmin prepared in 0.9% saline for injection | 20 |
| Plasminogen Activator Blinded Group E PA administered for 5 hours at a dose and volume according to the Investigator's clinical judgement/standard practice
Plasminogen Activator: Plasminogen activator used according to the Investigator's clinical judgment. | 9 |
| PA Placebo Blinded Treatment Arm F PA placebo (normal saline for injection) administered for 5 hours at a dose and volume according to the Investigator's clinical judgement/standard practice for PA administration
Placebo: Normal saline for injection at the same volume as the plasminogen activator. | 10 |
| Plasmin Open-label Treatment Group G Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 60 mL/hour infusion rate
Plasmin: Plasmin prepared in 0.9% saline for injection | 13 |
| Plasmin Open-label Treatment Group H Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 75 mL/hour infusion rate
Plasmin: Plasmin prepared in 0.9% saline for injection | 12 |
| Plasmin Open-label Treatment Group I Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter
Plasmin: Plasmin prepared in 0.9% saline for injection | 23 |
| Plasmin Open-label Treatment Group J Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 35 mL/hour infusion rate with balloon occlusion catheter
Plasmin: Plasmin prepared in 0.9% saline for injection | 19 |
| Plasmin Open-label Treatment Group M Open-label 250 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter
Plasmin: Plasmin prepared in 0.9% saline for injection | 6 |
| Total | 174 |
Baseline characteristics
| Characteristic | Plasmin Open-label Treatment Group B | Plasmin Open-label Treatment Group C | Plasmin Open-label Treatment Group D | Plasminogen Activator Blinded Group E | PA Placebo Blinded Treatment Arm F | Plasmin Open-label Treatment Group G | Plasmin Open-label Treatment Group H | Plasmin Open-label Treatment Group I | Plasmin Open-label Treatment Group J | Plasmin Open-label Treatment Group A | Plasmin Open-label Treatment Group M | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized <65 years | 10 participants | 10 participants | 10 participants | 5 participants | 5 participants | 8 participants | 7 participants | 13 participants | 12 participants | 12 participants | 3 participants | 95 participants |
| Age, Customized >=65 years | 10 participants | 12 participants | 10 participants | 4 participants | 5 participants | 5 participants | 5 participants | 10 participants | 7 participants | 8 participants | 3 participants | 79 participants |
| Gender Female | 3 Participants | 5 Participants | 7 Participants | 0 Participants | 3 Participants | 2 Participants | 3 Participants | 7 Participants | 5 Participants | 3 Participants | 1 Participants | 39 Participants |
| Gender Male | 17 Participants | 17 Participants | 13 Participants | 9 Participants | 7 Participants | 11 Participants | 9 Participants | 16 Participants | 14 Participants | 17 Participants | 5 Participants | 135 Participants |
| Region of Enrollment Belgium | 1 participants | 3 participants | 2 participants | 2 participants | 2 participants | 1 participants | 0 participants | 1 participants | 0 participants | 3 participants | 0 participants | 15 participants |
| Region of Enrollment Bulgaria | 1 participants | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants | 5 participants |
| Region of Enrollment Czech Republic | 4 participants | 3 participants | 5 participants | 1 participants | 1 participants | 5 participants | 5 participants | 9 participants | 7 participants | 4 participants | 1 participants | 45 participants |
| Region of Enrollment Germany | 0 participants | 1 participants | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Region of Enrollment India | 2 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 4 participants |
| Region of Enrollment Peru | 0 participants | 0 participants | 3 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 4 participants |
| Region of Enrollment Poland | 1 participants | 1 participants | 2 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 5 participants |
| Region of Enrollment Romania | 0 participants | 3 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Region of Enrollment Serbia | 7 participants | 3 participants | 4 participants | 4 participants | 6 participants | 4 participants | 5 participants | 1 participants | 3 participants | 6 participants | 0 participants | 43 participants |
| Region of Enrollment Slovakia | 2 participants | 4 participants | 1 participants | 1 participants | 0 participants | 2 participants | 2 participants | 11 participants | 9 participants | 3 participants | 5 participants | 40 participants |
| Region of Enrollment Ukraine | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment United States | 1 participants | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 5 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 20 | 11 / 20 | 18 / 22 | 14 / 20 | 7 / 9 | 8 / 9 | 7 / 13 | 5 / 12 | 12 / 21 | 10 / 17 | 3 / 6 |
| serious Total, serious adverse events | 10 / 20 | 4 / 20 | 6 / 22 | 4 / 20 | 2 / 9 | 5 / 9 | 4 / 13 | 3 / 12 | 7 / 21 | 2 / 17 | 0 / 6 |
Outcome results
Primary
The Proportion of Subjects With >50% Thrombolysis
The proportion of subjects with \>50% thrombolysis at the end of treatment compared to baseline by arteriography.
Time frame: 5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)
Population: In groups A-D, G and H, 8 subjects were excluded (EOT arteriogram missing or not read, did not receive \>=90% of dose). In groups I and J, 11 subjects were excluded (BOC not inserted/appropriately inflated, missing an arteriogram). In group F, 1 subject was not dosed and 4 subjects were excluded (did not receive \>=90% of dose).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plasmin Open-label Treatment Group A | The Proportion of Subjects With >50% Thrombolysis | 43.8 percentage of participants |
| Plasmin Open-label Treatment Group B | The Proportion of Subjects With >50% Thrombolysis | 47.4 percentage of participants |
| Plasmin Open-label Treatment Group C | The Proportion of Subjects With >50% Thrombolysis | 81.0 percentage of participants |
| Plasmin Open-label Treatment Group D | The Proportion of Subjects With >50% Thrombolysis | 47.4 percentage of participants |
| Plasminogen Activator Blinded Group E | The Proportion of Subjects With >50% Thrombolysis | 88.9 percentage of participants |
| PA Placebo Blinded Treatment Arm F | The Proportion of Subjects With >50% Thrombolysis | 40.0 percentage of participants |
| Plasmin Open-label Treatment Group G | The Proportion of Subjects With >50% Thrombolysis | 66.7 percentage of participants |
| Plasmin Open-label Treatment Group H | The Proportion of Subjects With >50% Thrombolysis | 66.7 percentage of participants |
| Plasmin Open-label Treatment Group I | The Proportion of Subjects With >50% Thrombolysis | 73.3 percentage of participants |
| Plasmin Open-label Treatment Group J | The Proportion of Subjects With >50% Thrombolysis | 42.9 percentage of participants |
| Plasmin Open-label Treatment Group M | The Proportion of Subjects With >50% Thrombolysis | 33.3 percentage of participants |
Secondary
The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability.
The incidence of major and minor bleeding events, deaths, adverse events, serious adverse events, and abnormal laboratory values as a measure of safety and tolerability.
Time frame: 30 days
Population: Subjects were excluded from the safety population if they did not receive any dose of Plasmin (groups I and J) or placebo (group F)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plasmin Open-label Treatment Group A | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 15.0 percentage of participants |
| Plasmin Open-label Treatment Group A | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 50.0 percentage of participants |
| Plasmin Open-label Treatment Group A | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 15.0 percentage of participants |
| Plasmin Open-label Treatment Group A | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 80.0 percentage of participants |
| Plasmin Open-label Treatment Group A | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 5.0 percentage of participants |
| Plasmin Open-label Treatment Group A | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 5.0 percentage of participants |
| Plasmin Open-label Treatment Group B | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 5.0 percentage of participants |
| Plasmin Open-label Treatment Group B | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 60.0 percentage of participants |
| Plasmin Open-label Treatment Group B | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 20.0 percentage of participants |
| Plasmin Open-label Treatment Group B | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 10.0 percentage of participants |
| Plasmin Open-label Treatment Group B | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 20.0 percentage of participants |
| Plasmin Open-label Treatment Group B | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 0 percentage of participants |
| Plasmin Open-label Treatment Group C | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 9.1 percentage of participants |
| Plasmin Open-label Treatment Group C | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 81.8 percentage of participants |
| Plasmin Open-label Treatment Group C | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 0 percentage of participants |
| Plasmin Open-label Treatment Group C | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 4.5 percentage of participants |
| Plasmin Open-label Treatment Group C | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 13.7 percentage of participants |
| Plasmin Open-label Treatment Group C | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 27.3 percentage of participants |
| Plasmin Open-label Treatment Group D | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 0 percentage of participants |
| Plasmin Open-label Treatment Group D | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 20.0 percentage of participants |
| Plasmin Open-label Treatment Group D | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 20.0 percentage of participants |
| Plasmin Open-label Treatment Group D | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 70.0 percentage of participants |
| Plasmin Open-label Treatment Group D | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 0 percentage of participants |
| Plasmin Open-label Treatment Group D | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 0 percentage of participants |
| Plasminogen Activator Blinded Group E | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 33.3 percentage of participants |
| Plasminogen Activator Blinded Group E | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 77.8 percentage of participants |
| Plasminogen Activator Blinded Group E | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 11.1 percentage of participants |
| Plasminogen Activator Blinded Group E | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 22.2 percentage of participants |
| Plasminogen Activator Blinded Group E | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 11.1 percentage of participants |
| Plasminogen Activator Blinded Group E | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 11.1 percentage of participants |
| PA Placebo Blinded Treatment Arm F | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 11.1 percentage of participants |
| PA Placebo Blinded Treatment Arm F | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 88.9 percentage of participants |
| PA Placebo Blinded Treatment Arm F | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 55.6 percentage of participants |
| PA Placebo Blinded Treatment Arm F | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 11.1 percentage of participants |
| PA Placebo Blinded Treatment Arm F | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 33.3 percentage of participants |
| PA Placebo Blinded Treatment Arm F | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 22.2 percentage of participants |
| Plasmin Open-label Treatment Group G | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 15.4 percentage of participants |
| Plasmin Open-label Treatment Group G | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 69.2 percentage of participants |
| Plasmin Open-label Treatment Group G | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 0 percentage of participants |
| Plasmin Open-label Treatment Group G | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 46.2 percentage of participants |
| Plasmin Open-label Treatment Group G | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 30.8 percentage of participants |
| Plasmin Open-label Treatment Group G | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 0 percentage of participants |
| Plasmin Open-label Treatment Group H | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 0 percentage of participants |
| Plasmin Open-label Treatment Group H | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 8.3 percentage of participants |
| Plasmin Open-label Treatment Group H | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 0 percentage of participants |
| Plasmin Open-label Treatment Group H | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 58.3 percentage of participants |
| Plasmin Open-label Treatment Group H | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 0 percentage of participants |
| Plasmin Open-label Treatment Group H | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 25.0 percentage of participants |
| Plasmin Open-label Treatment Group I | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 9.5 percentage of participants |
| Plasmin Open-label Treatment Group I | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 28.6 percentage of participants |
| Plasmin Open-label Treatment Group I | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 33.3 percentage of participants |
| Plasmin Open-label Treatment Group I | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 0 percentage of participants |
| Plasmin Open-label Treatment Group I | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 66.7 percentage of participants |
| Plasmin Open-label Treatment Group I | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 4.8 percentage of participants |
| Plasmin Open-label Treatment Group J | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 58.8 percentage of participants |
| Plasmin Open-label Treatment Group J | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 11.8 percentage of participants |
| Plasmin Open-label Treatment Group J | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 0 percentage of participants |
| Plasmin Open-label Treatment Group J | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 11.8 percentage of participants |
| Plasmin Open-label Treatment Group J | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 0 percentage of participants |
| Plasmin Open-label Treatment Group J | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 0 percentage of participants |
| Plasmin Open-label Treatment Group M | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Abnormal laboratory values | 0 percentage of participants |
| Plasmin Open-label Treatment Group M | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Adverse events | 50.0 percentage of participants |
| Plasmin Open-label Treatment Group M | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Major bleeding events | 0 percentage of participants |
| Plasmin Open-label Treatment Group M | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Serious adverse events | 0 percentage of participants |
| Plasmin Open-label Treatment Group M | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Minor bleeding events | 33.3 percentage of participants |
| Plasmin Open-label Treatment Group M | The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability. | Deaths | 0 percentage of participants |