Trial Outcomes & Findings for Safety and Tolerability Study of E-WE Thrombin in Healthy Adult Subjects (NCT NCT03453060)

NCT ID: NCT03453060

Last Updated: 2019-10-29

Results Overview

TEAEs will be determined by symptom driven physical examinations that can include assessment of the skin, head, ears, eyes, nose, throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 21 participants
• Primary outcome timeframe: one month
• Results posted on: 2019-10-29

Participant Flow

A total of 132 participants were screened for the study, of which 111 did not meet eligibility criteria, declined to participate, or were dropped alternates. The remaining 21 participants were randomized into the study, with each dose level occurring in sequential order.

Participant milestones

Measure	E-WE Thrombin Dose 1 Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 2 Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo Participants received a single intravenous dose of placebo.
Overall Study STARTED	4	4	4	4	5
Overall Study COMPLETED	4	4	4	4	5
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Tolerability Study of E-WE Thrombin in Healthy Adult Subjects

Baseline characteristics by cohort

Measure	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	Total n=21 Participants Total of all reporting groups
Age, Continuous	44.0 years n=93 Participants	37.3 years n=4 Participants	33.8 years n=27 Participants	36.0 years n=483 Participants	43.0 years n=36 Participants	39.0 years n=10 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	4 Participants n=36 Participants	14 Participants n=10 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	7 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants	4 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	4 Participants n=36 Participants	16 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	5 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	2 Participants n=10 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	4 Participants n=483 Participants	5 Participants n=36 Participants	18 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Region of Enrollment United States	4 participants n=93 Participants	4 participants n=4 Participants	4 participants n=27 Participants	4 participants n=483 Participants	5 participants n=36 Participants	21 participants n=10 Participants

PRIMARY outcome

Timeframe: one month

Population: Subjects who received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

TEAEs will be determined by symptom driven physical examinations that can include assessment of the skin, head, ears, eyes, nose, throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) Will be Summarized Using Frequency Counts.	0 Participants	0 Participants	3 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Body temperature will be measured in degrees Celsius. Clinically significant changes in body temperature are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Body Temperature, Frequency, and Relation to Treatment Will be Assessed.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Respiratory rate will be measured in breaths per minute. Clinically significant changes in respiratory rate are determined by the PI.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Respiratory Rate, Frequency, and Relation to Treatment Will be Assessed.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Systolic and diastolic blood pressure will be measured in mmHg. Clinically significant changes in systolic and diastolic blood pressure are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Blood Pressure (Systolic and Diastolic), Frequency, and Relation to Treatment Will be Assessed.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Heart rate will be measured in beats per minute. Clinically significant changes in heart rate are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Heart Rate, Frequency, and Relation to Treatment Will be Assessed.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

12-lead electrocardiogram measurement. Abnormal electrocardiograms are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Abnormal Electrocardiogram and Frequency and/ or Adverse Events That Are Related to Treatment.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: one month

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Plasma aPTT will be measured in seconds. Clinically significant changes in aPTT are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Activated Partial Thromboplastin Time (aPTT), Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: one month

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Prothrombin time will be measured in seconds. Clinically significant changes in prothrombin time are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Prothrombin Time, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: one month

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Thrombin time will be measured in seconds. Clinically significant changes in thrombin time are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Thrombin Time, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: one month

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Plasma fibrinogen levels will be measured in mg/dL. Clinically significant changes in plasma fibrinogen levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Plasma Fibrinogen, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Coagulation Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Injection site reaction assessment (pain, tenderness, erythema/ redness, and induration/ swelling.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Injection Site Reaction and/ or Adverse Events That Are Related to Treatment.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: one month

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Immunogenicity measured by plasma anti-drug antibodies.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects That Develop Treatment-related Immunogenicity.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

BUN levels in the blood will be measured in mg/dL. Clinically significant changes in BUN are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Blood Urea Nitrogen Levels (BUN) as Part of a Standard Serum Chemistry Panel, Frequency, and Relation to Treatment Will be Assessed.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Bilirubin (total and direct) levels in the blood will be measured in mg/dL. Clinically significant changes in total and direct bilirubin levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Bilirubin (Total and Direct) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Alkaline phosphatase levels in the blood will be measured in U/L. Clinically significant changes in alkaline phosphatase levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Alkaline Phosphatase Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

AST levels in the blood will be measured in U/L. Clinically significant changes in AST levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Aspartate Aminotransferase (AST) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

ALT levels in the blood will be measured in U/L. Clinically significant changes in ALT levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Alanine Aminotransferase (ALT) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

LDH levels in the blood will be measured in U/L. Clinically significant changes in LDH levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Lactate Dehydrogenase (LDH) Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days.

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Albumin levels in the blood will be measured in g/dL. Clinically significant changes in albumin levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Albumin Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Sodium levels will be measured in mEq/L. Clinically significant changes in sodium levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Sodium Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Potassium levels will be measured in mEq/L. Clinically significant changes in potassium levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Potassium Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Chloride levels will be measured in mEq/L. Clinically significant changes in chloride levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Chloride Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Bicarbonate levels will be measured in mEq/L. Clinically significant changes in bicarbonate levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Bicarbonate Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Blood glucose levels will be measured in mg/dL. Clinically significant changes in blood glucose levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Glucose Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Creatinine levels will be measured in mg/dL. Clinically significant changes in creatinine levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Creatinine Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Serum Chemistry Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Hemoglobin levels will be measured in g/dL. Clinically significant changes in hemoglobin levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Hemoglobin Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Hematocrit levels will be measured in %. Clinically significant changes in hematocrit levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Hematocrit Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days.

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Total leukocyte counts will be measured in 10˄3/uL. Clinically significant changes in leukocyte counts are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Total Leukocyte Counts, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days.

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Differential leukocyte counts will be measured in %. Clinically significant changes in differential leukocyte counts are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Differential Leukocyte Counts, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Red blood cell count will be measured in 10˄6/uL. Clinically significant changes in red blood cell counts are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Red Blood Cell Count, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Platelet count will be measured in 10˄3/uL. Clinically significant changes in platelet counts are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Platelet Count, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Hematology Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

pH of the urine will be measured. Clinically significant changes in urine pH are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine pH, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Specific gravity of the urine will be evaluated. Clinically significant changes in specific gravity are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine Specific Gravity, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Protein levels in the urine will be evaluated. Clinically significant changes in protein levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine Protein Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Glucose levels in the urine will be evaluated. Clinically significant changes in urine glucose are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine Glucose Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Ketone levels in the urine will be evaluated. Clinically significant changes in urine ketone levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine Ketone Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Bilirubin levels in the urine will be evaluated. Clinically significant changes in urine bilirubin levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine Bilirubin Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Blood levels in the urine will be evaluated. Clinically significant changes in urine blood levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine Blood Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Nitrite levels in the urine will be evaluated. Clinically significant changes in urine nitrite levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine Nitrite Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Urobilinogen levels in the urine will be evaluated. Clinically significant changes in urine urobilinogen levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine Urobilinogen Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: two days

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Leukocyte esterase levels in the urine will be evaluated. Clinically significant changes in urine leukocyte esterase levels are determined by the PI or designee.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Number of Subjects With Clinically Significant Changes in Urine Leukocyte Esterase Levels, Frequency, and Relation to Treatment Will be Assessed as Part of a Standard Urinalysis Panel.	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Predose, 0.08, 0.25, 0.5, 1, 2, 4, and 24h post-dose

Population: Subjects who had received any dose of study drug or placebo were included in the as-treated population and subjects were analyzed according to the treatment they actually received.

Plasma APC-PCI levels will be measured in ng/mL.

Outcome measures

Measure	E-WE Thrombin Dose 2 n=4 Participants Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 Participants Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 Participants Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 Participants Participants received a single intravenous dose of placebo.	E-WE Thrombin Dose 1 n=4 Participants Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.
The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI). predose	1.3 ng/mL Standard Deviation 0.7	2.0 ng/mL Standard Deviation 0.7	1.0 ng/mL Standard Deviation 0.0	1.5 ng/mL Standard Deviation 0.7	1.8 ng/mL Standard Deviation 0.9
The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI). 0.08 hours post dose	123.0 ng/mL Standard Deviation 5.0	195.3 ng/mL Standard Deviation 16.8	283.3 ng/mL Standard Deviation 61.2	1.7 ng/mL Standard Deviation 0.9	61.8 ng/mL Standard Deviation 16.3
The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI). 0.25 hours post dose	218.3 ng/mL Standard Deviation 4.6	364.8 ng/mL Standard Deviation 86.4	579.0 ng/mL Standard Deviation 82.0	1.2 ng/mL Standard Deviation 0.5	108.2 ng/mL Standard Deviation 20.5
The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI). 0.5 hours post dose	229.8 ng/mL Standard Deviation 19.4	470.8 ng/mL Standard Deviation 140.9	678.3 ng/mL Standard Deviation 84.8	1.3 ng/mL Standard Deviation 0.6	122.0 ng/mL Standard Deviation 18.6
The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI). 1 hour post dose	194.5 ng/mL Standard Deviation 24.2	328.8 ng/mL Standard Deviation 94.0	480.5 ng/mL Standard Deviation 33.6	1.2 ng/mL Standard Deviation 0.5	90.9 ng/mL Standard Deviation 12.9
The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI). 2 hours post dose	56.2 ng/mL Standard Deviation 14.8	124.5 ng/mL Standard Deviation 40.4	132.3 ng/mL Standard Deviation 17.4	1.2 ng/mL Standard Deviation 0.5	27.3 ng/mL Standard Deviation 3.8
The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI). 4 hours post dose	5.9 ng/mL Standard Deviation 1.3	12.7 ng/mL Standard Deviation 6.2	15.2 ng/mL Standard Deviation 4.3	1.0 ng/mL Standard Deviation 0.0	3.5 ng/mL Standard Deviation 0.5
The Effect of a Single Intravenous Dose of E-WE Thrombin on Generation of Activated Protein C- Protein C Inhibitor Complexes (APC-PCI). 24 hours post dose	1.0 ng/mL Standard Deviation 0.0	1.7 ng/mL Standard Deviation 0.9	1.0 ng/mL Standard Deviation 0.0	1.6 ng/mL Standard Deviation 0.8	1.0 ng/mL Standard Deviation 0.0

Adverse Events

E-WE Thrombin Dose 1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

E-WE Thrombin Dose 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

E-WE Thrombin Dose 3

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

E-WE Thrombin Dose 4

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	E-WE Thrombin Dose 1 n=4 participants at risk Participants received a single intravenous dose of 0.5 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 2 n=4 participants at risk Participants received a single intravenous dose of 1.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 3 n=4 participants at risk Participants received a single intravenous dose of 2.0 mcg/kg E-WE Thrombin.	E-WE Thrombin Dose 4 n=4 participants at risk Participants received a single intravenous dose of 4.0 mcg/kg E-WE Thrombin.	Placebo n=5 participants at risk Participants received a single intravenous dose of placebo.
General disorders Vessel puncture site haemorrhage	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	25.0% 1/4 • Number of events 1 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/5 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.
Nervous system disorders Headache	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	50.0% 2/4 • Number of events 2 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/5 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.
Psychiatric disorders Insomnia	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	25.0% 1/4 • Number of events 1 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/5 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	0.00% 0/4 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.	20.0% 1/5 • Number of events 1 • Adverse events were recorded from subject check-in through follow up which occurred on Day 28. Subjects were monitored throughout confinement for adverse reactions to the study drug and/or procedures. Subjects were asked how they are feeling and were encouraged to report AEs during confinement and at each follow-up visit.

Additional Information

Norah G. Verbout, Senior Scientist and Project Manager

Aronora, Inc.

Phone: 503-964-0250

Email: norah.verbout@aronorabio.com

Results disclosure agreements

• Principal investigator is a sponsor employee Aronora, Inc. shall retain title to and the right to publish all documentation, records, raw data, specimens, or other work product generated in connection with this study. Such publications shall not be made by the PI or Celerion without the prior written consent of Aronora, Inc.
• Publication restrictions are in place

Restriction type: OTHER