Clinical trial NCT01945606: Study to Assess the Safety of BAY1067197 in Stable Heart Failure Patients on Standard Therapy Including ß-blocker
Official title: A Single Blind, Placebo Controlled Pilot Study to Explore the Safety and Tolerability of a Single Oral Dose of 30 mg BAY1067197 in Patients With Chronic Heart Failure on the Background of Preexisting Beta-blocker Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-09-18
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study to investigate the safety and tolerability of the partial A1 agonist BAY1067197 in patients with chronic heart failure. BAY1067197 will be applied as a single dose of 30 mg in addition to standard therapy including a beta-blocker. The aim of the study is to assess if a single oral dose of 30 mg BAY1067197 is well tolerated when given on top of standard therapy for heart failure, particularly ß-blocker treatment.


Eligibility criteria: Inclusion Criteria:

* Stable systolic heart failure (heart failure with reduced ejection fraction, heart failure with reduced ejection fraction \[HFrEF\]; New York Heart Association \[NYHA\] I-III) in sinus rhythm with a documented ejection fraction (EF) ≤45% within the last 3 months
* Stable standard heart failure (HF) therapy including intermediate to high dose β-blocker with either ≥ 95 mg metoprolol succinate (controlled release tablet), ≥ 5mg Bisoprolol (immediate release \[IR\] -tablet) or ≥5mg Nebivolol (IR tablet) for at least 4 weeks. Additional intake of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers and optional aldosterone-receptor antagonists, diuretics or digitalis is allowed
* Men or confirmed postmenopausal women (defined as being amenorrheic for longer than 2 years with an appropriate clinical profile, e.g. age appropriate and a history of vasomotor symptoms) or women without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy (documented by medical report verification). Men enrolled in this study must agree to use adequate barrier birth control measures during the treatment period of the study and for 12 weeks after receiving the investigational medicinal product (IMP)
* Male patients must agree not to act as sperm donor for 12 weeks after dosing
* Ethnicity: White
* Body mass index (BMI): above/equal 18.0 and below/equal 29.9 kg/m²
* Age: 18 to 75 years (inclusive) at the first screening visit

Exclusion Criteria:

* Biventricular pacing/active cardiac resynchronization therapy (CRT) device
* Dependency on pacemaker or implantable cardioverter-defibrillator (ICD) device with pacemaker dependency (a paced ventricular rhythm \> 5% of heart activity)
* A history of relevant diseases of vital organs other than the heart, of the central nervous system or other organs
* Known hypersensitivity to the study preparations (active substances or excipients of the preparations) or to any other β-blocker
* Current or history of AV-Block \> I°
* Unstable condition, indicated by requirement of IV drug (diuretic, inotrope, etc.) or NYHA IV
* Acute Coronary Syndrome (defined as unstable angina \[UA\], non-ST elevation myocardial infarction \[NSTEMI\], ST elevation myocardial infarction \[STEMI\]) within 3 months prior to first study drug administration
* History of asthma or chronic obstructive pulmonary disease (COPD) ≥ global initiative for chronic obstructive lung disease (GOLD) II and/or allergic asthma
* Women of childbearing potential, pregnancy or breastfeeding

Primary outcomes:
measure: Number of patients with occurrence of AV-Block > I°
timeFrame: up to 48 hours
Secondary outcomes:
measure: Pharmacokinetic profile determined by tmax
timeFrame: up to 24 hours
measure: Pharmacokinetic profile determined by t1/2
timeFrame: up to 22 days
measure: Heart rate
timeFrame: multiple time points up to 24 hours
measure: Blood pressure
timeFrame: multiple time points up to 24 hours
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: up to 48 hours
Other outcomes:
Locations:
city: Groningen
country: Netherlands
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: