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

• Conditions: Heart failure; MedDRA version: 14.1Level: LLTClassification code 10000803Term: Acute heart failureSystem Organ Class: 10007541 - Cardiac disorders; MedDRA version: 14.1Level: HLGTClassification code 10019280Term: Heart failuresSystem Organ Class: 10007541 - Cardiac disorders; MedDRA version: 14.1Level: LLTClassification code 10064081Term: Heart failure NYHA class IIISystem Organ Class: 10007541 - Cardiac disorders; MedDRA version: 14.1Level: LLTClassification code 10064082Term: Heart failure NYHA class IVSystem Organ Class: 10007541 - Cardiac disorders; MedDRA version: 14.1Level: LLTClassification code 10010684Term: Congestive heart failureSystem Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2010-020376-37-CZ
• Lead Sponsor: Trevena, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01-26
• Last Update Posted: 12 May 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1) Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
2) Male or female, age = 18 and = 65 years. Males must agree to use appropriate birth control measures including condoms for at least 1 week following participation in the study (Section 7.3). Females must be of non-childbearing potential as defined below.
a) Pre-menopausal females with documented (medical report verification) hysterectomy or bilateral oophrectomy, or
b) Post-menopausal females with at least 12 months of spontaneous amenorrhea; or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels = 40 IU/L or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
3) Diagnosis of congestive heart failure made at least 3 months prior to screening and confirmed with at least one elevated BNP (or NT-proBNP) concentration (greater than laboratory reference range) performed within 3 months of IMP administration (may be obtained during screening).
4) Ejection fraction = 35% as measured using any quantitative imaging modality (e.g. echocardiography, radionuclide imaging, MRI, CT) within 3 months prior to screening.
5) NYHA Class III or IV heart failure, and in the opinion of the investigator, right-heart catheterization is clinically indicated.
6) Systolic blood pressure at screening taken after at least 10 minutes at rest must be = 100 mmHg. Heart rate at screening taken after at least 10 minutes at rest must be < 90 bpm. The blood pressure and/or heart rate may be repeated if the Investigator believes that including the subject will not pose unacceptable risk to the subject or compromise interpretation of the tolerability or pharmacodynamic data.
7) Oxygen saturation = 94% on room air (= 92% for high altitude locations).
8) Weight = 125 kg at baseline.
9) For males, serum creatinine = 1.8 mg/dL (= 160 µmol/L); for females, serum creatinine = 1.5 mg/dL (133 µmol/L).
10) Clinical laboratory tests within the lab reference ranges or within clinically acceptable limits as determined by the Investigator.
11) Baseline mean PCWP = 20 mmHg with three consecutive measures where the highest and lowest values are within 4 mmHg of each other.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

Subjects will be excluded if any of the following apply:
1) 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.
2) Presence of clinically significant anemia at screening.
3) Any other serious life threatening disease, for example uncontrolled or poorly controlled seizure disorder, poorly controlled diabetes mellitus, chronic obstructive pulmonary disease, that may impair the interpretation of safety or efficacy data from the study.
4) Contraindication to the placement of a PAC, or placement of PAC not feasible
5) Medications:
a) Has received an intravenous vasodilator (e.g. nitroglycerin, nitroprusside, nesiritide) within 24 hours of initiating IMP.
b) Has received any dose of an intravenous inotrope or chronotrope (e.g. milrinone, dobutamine) within 48 hours of initiating IMP.
c) Use of a phosphodiesterase type-5 (PDE5) inhibitor (e.g. sildenafil, vardenafil, tadalafil) within 1 week of initiating IMP.
d) Use of angiotensin receptor blocking drugs within 7 days of initiating IMP.
e) Use of any investigational medication within 30 days or 5 half-lives (whichever is longer) within 30 days prior to IMP administration.
6) Uncorrected and hemodynamically significant aortic or mitral stenosis, or aortic regurgitation.
7) Clinical signs or symptoms of cardiogenic shock.
8) Current signs or symptoms of acute myocardial ischemia.
9) Acute coronary syndrome (ACS) or coronary revascularization in the past 3 months.
10) Complex congenital heart disease.
11) Primary myocardial infiltrative disease (e.g. hypertrophic cardiomyopathy, amyloidosis, sarcoidosis, hemochromatosis).
12) Sustained or uncontrolled ventricular arrhythmia. Inclusion of patients with atrial fibrillation with a heart rate = 90 bpm is permitted.
13) Ventricular assist device or intra-aortic balloon pump in place.
14) Ultrafiltration at time of randomization.
15) Post-cardiac or renal transplant.
16) Major surgery within 8 weeks prior to IMP administration.
17) Stroke in the past 6 months.
18) Allergy or intolerance of angiotensin receptor blockers or ACE inhibitors.
19) Illicit drug use within 6 months of IMP initiation.
20) Pregnant or lactating.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified