Multiple Dose Study in Heart Failure of BAY 1067197 (PARSiFAL)

Bayer

Status and phase: Completed; Phase 2

Conditions: Heart Failure

Treatments: Drug: Placebo (10 mg); Drug: BAY1067197 (10 mg); Drug: Placebo; Drug: BAY1067197

Study type: Interventional

Funder types: Industry

Identifiers

NCT02040233

16782

2013-002522-23 (EudraCT Number)

Details and patient eligibility

About

This is a study to investigate the safety, tolerability and early effects on cardiac function of the partial A1 agonist BAY1067197 in patients with chronic heart failure. BAY1067197 will be applied once daily over 7 days in addition to standard therapy including a beta-blocker. The aim of the study is to assess if a 7 day treatment with BAY1067197 is well tolerated when given on top of standard therapy for heart failure. Furthermore, the study aims to assess if cardiac function improves in the early course of therapy.

Enrollment: 31 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• Inclusion Criteria:
• Clinical diagnosis of chronic systolic heart failure of ischemic or non-ischemic etiology:(New York Heart Association)NYHA class I-III and treatment with standard pharmacological therapy for the treatment of systolic heart failure including β-blocker ≥ 4 weeks prior to randomization
• Left ventricular ejection fraction ≤ 40%: by any imaging technique within the last 3 months will be accepted for screening purposes but will be verified by baseline CMR(Cardiac Magnetic Resonance Tomography)
• Sinus rhythm for at least 4 weeks prior to randomization
• No planned changes to heart failure related drug therapy for the duration of study drug treatment
• Substantial dysfunctional but viable myocardium as demonstrated by the baseline CMR: Based on a standard 17-segment model (AHA - American Heart Association), 3 or more segments require demonstration of dysfunction (defined by visible assessment of the performing investigator) and viability (defined as < 25% of segment area with scar burden - in patients with CAD (Coronary Artery Disease) or no (i.e. zero) scar burden in patients without CAD [idiopathic CM patient])
• Men or confirmed postmenopausal women or women without childbearing potential.
• Age: 18 to 75 years (inclusive) at the first screening visit.
• Body Mass Index (BMI) :above /equal 18.0 and below/equal 34.9kg/m²
• Exclusion Criteria:
• Atrial fibrillation / atrial flutter within the last 4 weeks prior to randomization or currently persistent/permanent atrial fibrillation / atrial flutter
• Primary valvular disease (severe valvular disease) with planned valve repair or replacement
• Non-idiopathic non-ischemic causes for cardiomyopathy (constrictive, restrictive, or hypertrophic cardiomyopathy; acute myocarditis)
• Listing for heart transplantation and/or anticipated/implanted ventricular assist device Clinically relevant ventricular arrhythmias within the last 2 months (sustained ventricular tachycardia, ventricular flutter or fibrillation), based on either medical history or ICD-testing results (if applicable)
• Unstable cardiac condition, indicated by requirement of IV drug (diuretic, inotrope, etc.) or NYHA IV within 4 weeks prior to randomization
• Coronary revascularization within 4 weeks prior to randomization or if revascularization is anticipated or needed
• Current permanent or intermittent AV-Block > I° or history of AV-Block > I° within six months before enrollment
• PR duration ≥ 300 ms
• Acute Coronary Syndrome (defined as unstable angina [UA], non-ST elevation myocardial infarction [NSTEMI], ST elevation myocardial infarction [STEMI]) within 2 months prior to randomization
• Subjects with untreated hyperthyroidism or hypothyroidism and non-stable thyroid function (intake of stable thyroid hormone substitution allowed)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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31 participants in 4 patient groups, including a placebo group

BAY1067197 (10 mg)

Active Comparator group

Treatment:

Drug: BAY1067197 (10 mg)

BAY1067197

Active Comparator group

Treatment:

Drug: BAY1067197

Placebo (10 mg)

Placebo Comparator group

Treatment:

Drug: Placebo (10 mg)

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo