Pharmacokinetics and Pharmacodynamics of MTR105 in Hypotensive Cardiac Surgery Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, pharmacokinetic and the pharmacodynamic effects of escalating doses of MTR105 while weaning from bypass in a hypotensive population of cardiac surgery patients.

Detailed Description
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The study is a prospective, randomized, four-arm, dose-escalating, double blind, placebo controlled study evaluating the safety, pharmacokinetics, and pharmacodynamics of four dose levels of MTR105 in patients undergoing cardiac surgery utilizing cardiopulmonary bypass presenting hypotension upon weaning off bypass.

Official Title
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A Phase II, Randomized, Double Blind, Placebo-controlled, Dose-escalating Study to Assess the Pharmacokinetics and Pharmacodynamics of MTR105 in Cardiac Surgery Induced Hypotension Patients During Weaning Off Cardiopulmonary Bypass

Conditions
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Hypotension, Cardiopulmonary Bypass

Intervention / Treatment
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* Drug: MTR105


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women age 18 years or older Referred for cardiac surgery requiring the use of CPB. Elective or urgent surgeries (non emergency operations). LVEF ≥40 based on cardiac catheterization results Normal renal function at study entry Normal hepatic function (within normal laboratory ranges) at study entry Normal coagulation status at study entry as judged by PT, PTT, fibrinogen and platelet count. Willingness to participate in the study and adhere to the study design. Willingness to sign an informed consent form. Exclusion Criteria: Emergency operation Pulmonary hypertension (PA systolic pressure >60 mmHg) Ejection fraction less than 35% during weaning from bypass or cardiac index of less than 1.8 Neurological events such as prior CVA, TIA or symptomatic carotid stenosis within 1 year of presenting for surgery Body weight <40 Kg Pregnancy Malignancy within 1 year of presenting for surgery Systemic infection as evidenced by elevated WBC or fever >38.5 C Usage of vasoactive medications within 24 hours except short term use of a vasoconstrictor during induction. Participation in any other investigational drug or device study within 30 days of randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>Dose level 0.3 mg/kg with 6 active and 2 placebo | Drug: MTR105<br>* Intravenous administration, dose escalating (4 arms), single dose<br>|
| Other: 2<br>Dose level 0.6 mg/kg 6 patients active and 2 placebo | Drug: MTR105<br>* Intravenous administration, dose escalating (4 arms), single dose<br>|
| Other: 3<br>Dose level 1.2 mg/kg 6 active and 2 placebo | Drug: MTR105<br>* Intravenous administration, dose escalating (4 arms), single dose<br>|
| Other: 4<br>Dose level 2.4 mg/kg 6 active and 2 placebo | Drug: MTR105<br>* Intravenous administration, dose escalating (4 arms), single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic parameters |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics |  | 10 hours |