Study of Single Doses of IV Aerucin in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the safety profile and pharmacokinetic behavior of a single administration of Aerucin in healthy adults at three different dosages.

Detailed Description
-----------------
This Phase I trial will be conducted as an open label trial in 15 healthy adults. All subjects will receive a specific intravenous dose of Aerucin. There are three study groups, each with a specific dose of Aerucin. Study Group 1 will receive 2.0 mg/ kg of Aerucin . Study Group 2 will receive 8.0 mg/kg of Aerucin . Study Group 3 will receive 20 mg/kg of Aerucin . The dose levels of Aerucin are selected for this study based on animal studies showing protection in an animal model and absence of adverse effects in toxicological studies. Groups will be enrolled sequentially.

Official Title
-----------------
A Phase 1 Single-center (U.S.), Open Label, Dose-escalation Study of the Safety and Pharmacokinetics of Single Doses of Intravenous AerucinTM in Healthy Adult Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Biological: Aerucin 2.0mg/kg
* Biological: Aerucin 8.0mg/kg
* Biological: Aerucin 20.0 mg/kg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has completed the written informed consent process Is male or female Is age ≥18 years and ≤50 years Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study Agrees to avoid elective surgery for the duration of the study For female subjects: agrees to have avoided pregnancy from 14 days prior to Study Day 0 through the duration of the study. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include: a sterile sexual partner; sexual abstinence (not engaging in any sexual intercourse); hormonal contraceptives (oral, injection, transdermal patch, or implant); vaginal ring; intrauterine device (IUD); or condom. Has general good health, confirmed by medical history and physical examination Has body mass index (BMI) between 18 and 30 (weight/height) - Exclusion Criteria: Oral temperature ≥37.5°C Abnormal CBC laboratory values (per local laboratory parameters) from blood collected at screening (>5% above ULN or >5% below LLN) Abnormally elevated laboratory values (per local laboratory parameters) from blood collected at screening for ALT, AST, total bilirubin, alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (Cr), (>10% above ULN) Abnormal urinalysis that, in the opinion of the investigator, is clinically significant Positive screening urine test for illicit drugs (opiates, cocaine, amphetamines) Has received an immunoglobulin product in the 120 days prior to Study Day 0 History or evidence of autoimmune disease History or evidence of any past, present, or future possible immunodeficiency state, including laboratory evidence of HIV 1 infection. History or evidence of chronic hepatitis History of evidence of Pseudomonas infection Received a systemic antibiotic with 14 days prior to Study Day 0 Participation in any other investigational study during the study period Received immunoglobulin or blood products within 90 days prior to Study Day 0 Received any investigational drug therapy or investigational drug within 60 days prior to Study Day 0 Received immunosuppressive medications other than inhaled or topical immunosuppressants within 45 days prior to Study Day 0 Inability to discontinue daily medications during the study other than: oral contraceptives, vitamins, nonprescription nutritional supplements, aspirin, antihistamines inhaled corticosteroids, inhaled beta agonists, inhaled anticholinergics All female subjects: currently pregnant or lactating/nursing; positive screening urine pregnancy test; or positive urine pregnancy test on the day of any study dosing History or evidence of allergic disease or reaction that, in the opinion of the investigator, may compromise the safety of the subject History or evidence of any other acute or chronic disease that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the drug or compromise the safety of the subject Medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol Any other reason at discretion of the investigator -

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Aerucin 2.0mg/kg | Biological: Aerucin 2.0mg/kg<br>* IV Aerucin 2.0 mg/kg over 1 hour<br>|
| Experimental: Group 2<br>Aerucin 8.0mg/kg | Biological: Aerucin 8.0mg/kg<br>* IV Aerucin 8.0 mg/kg over 1 hour<br>|
| Experimental: Group 3<br>Aerucin 20.0mg/kg | Biological: Aerucin 20.0 mg/kg<br>* IV Aerucin 20 mg/kg over 1 hour<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number and % of subjects experiencing adverse events following dosing | 28 and 84 days following dosing | 
| Serious Adverse Events | Number and % of subjects experiencing Serious Adverse Events following dosing | 24 and 84 days following dosing | 
| Solicited Adverse Events | Number and % of subjects experiencing Solicited Adverse Events following dosing | 7 days following dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CMax -Observed maximum plasma concentration | Pharmacokinetics Characteristics | 84 days following dosing | 
| TMax-Time to reach maximum plasma concentration | Pharmacokinetics Characteristics | 84 days following dosing | 
| AUC0-last Area under the the concentration time curve | Pharmacokinetics Characteristics | 84 days following dosing | 
| AUC0-∞ Area under the concentration time curve from zero to infinite time | Pharmacokinetics Characteristics | 84 days following dosing | 
| Terminal phase elimination rate | Pharmacokinetics Characteristics | 84 days following dosing | 
| Terminal elimination half-life | Pharmacokinetics Characteristics | 84 days following dosing |