Study to Evaluate the Effects of TRV120027 in Patients With Heart Failure

Study Overview
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Brief Summary
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In this study, TRV120027 (or a placebo) intravenous infusion will be given to people with heart failure to learn about the effects of TRV120027. The results of this study will help choose the proper range of TRV120027 doses to use in future research studies involving patients with acute decompensated heart failure.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Adaptive, Ascending Dose-Titration Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Invasive Hemodynamics of TRV120027 in Patients With Stable Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: TRV120027
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of congestive heart failure made at least 3 months prior to screening NYHA Class III or IV heart failure, ejection fraction </= 35% and , and in the opinion of the investigator, right-heart catheterization is clinically indicated. Baseline mean PCWP >/= 20 mmHg Systolic blood pressure at screening must be >/= 100 mmHg. Heart rate at screening must be </= 90 bpm. Exclusion Criteria: Any significant disease or condition that would interfere with the interpretation of safety or efficacy in this study as determined by the Investigator based on medical history, physical examination or laboratory tests. Significant valve disease Current signs or symptoms of acute myocardial ischemia or acute coronary syndrome (ACS) or coronary revascularization in the past 3 months. Sustained or uncontrolled ventricular arrhythmia. Inclusion of patients with atrial fibrillation with a heart rate ≤ 90 bpm is permitted.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRV120027<br> | Drug: TRV120027<br>* Dose range (starting at 0.1 mcg/kg/min) of TRV120027 administered for 14 hours.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo administered for 14 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Capillary Wedge Pressure (PCWP) | The effect of TRV120027 on pulmonary capillary wedge pressure will be compared to baseline and to placebo at multiple measurement time points during the 14 hour infusion and for 4 hours after discontinuation of the infusion. | Multiple time points during 14 hr infusion and during 4 hr period after end of infusion | 
| Safety and Tolerability | Safety and tolerability will be assessed qualitatively by evaluating adverse events, clinical laboratories, ECGs, cardiac telemetry and vital signs at multiple measurement time points during the 14 hour infusion and for 4 hours after discontinuation of the infusion. Follow-up assessments for adverse events at Day 7 and Day 30 will be conducted. | Multiple time points during 14 hr infusion and during 4 hr period after end of infusion, and follow-up (Day 7, Day 30) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of TRV120027 | PK samples will be collected at multiple time points during the 14 hour infusion and 4 hour washout periods. | Multiple time points during 14 hr infusion and during 4 hr period after end of infusion | 
| Additional Hemodynamics | Additional hemodynamic variables (for example, right atrial pressure, pulmonary arterial pressure and cardiac output) will be compared to baseline and to placebo at multiple measurement time points during the 14 hour infusion and for 4 hours after discontinuation of the infusion. | Multiple time points during 14 hr infusion and during 4 hr period after end of infusion | 
| Laboratory Evaluations | Biomarkers of renal function and neurohormonal activation will be assessed at multiple measurement time points during the 14 hour infusion and for 4 hours after discontinuation of the infusion, and again at follow-up Day 7. | Multiple time points during 14 hr infusion and during 4 hr period after end of infusion, and follow-up (Day 7) |