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

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
TRV120027	TRV120027	-

Primary Outcome Measures

Name	Time	Method
Pulmonary Capillary Wedge Pressure (PCWP)	Multiple time points during 14 hr infusion and during 4 hr period after end of infusion	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.
Safety and Tolerability	Multiple time points during 14 hr infusion and during 4 hr period after end of infusion, and follow-up (Day 7, Day 30)	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.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of TRV120027	Multiple time points during 14 hr infusion and during 4 hr period after end of infusion	PK samples will be collected at multiple time points during the 14 hour infusion and 4 hour washout periods.
Additional Hemodynamics	Multiple time points during 14 hr infusion and during 4 hr period after end of infusion	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.
Laboratory Evaluations	Multiple time points during 14 hr infusion and during 4 hr period after end of infusion, and follow-up (Day 7)	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.

Locations (8): CZ05
🇨🇿
Brno, Czechia
CZ04
🇨🇿
Olomouc, Czechia
CZ06
🇨🇿
Prague, Czechia
PL01
🇵🇱
Warsaw, Poland
PL05
🇵🇱
Wroclaw, Poland
University of Maryland
🇺🇸
Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States