Clinical trial NCT02452515: A Single-blind Pilot Study to Investigate Safety and Tolerability of the Chymase Inhibitor BAY1142524 in Clinically Stable Patients With Left-ventricular Dysfunction
Official title: A Single-blind, Multicenter Pilot Study to Investigate the Safety and Tolerability of a 14 Day Oral Treatment With Different Doses of the Chymase Inhibitor BAY1142524 in Comparison to Placebo in Clinically Stable Patients With Left-ventricular Dysfunction After Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-05-22
Enrollment: 49
Sex: ALL
Minimum age (years): 40
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of the trial is the analysis of safety and tolerability of the chymase inhibitor BAY1142524 in comparison to placebo using a 2 weeks treatment period in clinically stable patients with left-ventricular dysfunction after myocardial infarction. BAY1142524 or placebo will be given on top of evidence-based standard of care for left-ventricular dysfunction after myocardial infarction. Primary objectives are the analysis of safety and tolerability as evidenced by the incidence and severity of adverse events. BAY1142524 will be administered in a parallel group design using four doses (5, 10, 25 mg twice daily, and 50 mg once daily). Each dose group consists of 9 patients treated with verum and 3 patients treated with placebo.


Eligibility criteria: Inclusion Criteria:

* Clinically stable patients with left-ventricular dysfunction (LVEF ≤ 45%) after myocardial infarction, whereby the MI occurred 6 or more months before randomization.

  * New York Heart Association (NYHA) class I-II.
  * Left-ventricular ejection fraction ≤ 45%, confirmed by any imaging technique within the last 3 months prior to screening visit will be accepted for screening purposes. If no data are available, an echocardiography has to be performed at screening for inclusion.
  * Treatment with evidence-based therapy for left-ventricular dysfunction post MI for at least 4 weeks prior to screening visit. This therapy has to include at least an Angiotensin-converting enzyme (ACE) inhibitor or an Angiotensin receptor blockers (ARB). Beta-blockers, diuretics, mineralocorticoid receptor antagonist (MRAs), antiplatelet therapy, statins, and aspirin are to be used if indicated. Treatment with stable doses of ACE inhibitors or ARBs using at least half of the recommended target dose (as defined in the European Society of Cardiology (ESC) guidelines, see appendix 16.4) ≥ 4 weeks prior to the screening visit is mandatory.
  * No planned changes to post MI drug therapy during the active treatment phase of the study.
  * 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 oophorectomy or hysterectomy (documented by medical report verification).

Men of reproductive potential must agree to use 2 reliable and acceptable methods for contraception simultaneously when sexually active and not to act as sperm donor. This applies for the time period between signing of the informed consent form and 12 weeks after the last administration of study drug.

Acceptable methods of contraception include, but are not limited to, (i) condoms (male or female) with or without a spermicidal agent; (ii) diaphragm or cervical cap with spermicide; (iii) intra-uterine device; (iv) hormone-based contraception.

* Age: 40 to 79 years (inclusive) at the screening visit.
* Race: Caucasian

Exclusion Criteria:

* Non-ischemic causes for cardiomyopathy will be excluded (including, but not limited to: primary cardiomyopathy, constrictive, restrictive or hypertrophic cardiomyopathy, acute myocarditis, cardiomyopathy secondary to cardiotoxic chemotherapeutic agents).
* Hospitalization for decompensated heart failure within the last 3 months prior to randomization.
* Coronary revascularization within 6 weeks prior to randomization or if revascularization is anticipated or needed during the study duration.
* Clinically relevant, cardiac ischemia in a stress test within 3 months before screening.
* Patients carrying implantable cardioverter defibrillators, cardiac resynchronisation therapy devices or left ventricular assist devices that had any significant clinical events requiring treatment or changes to background medical therapy such as ventricular tachycardias, ventricular fibrillation in the last 6 months before randomization while carrying the devices
* Primary and uncorrected valvular disease with foreseen requirement of valve repair within the next 6 months.
* Any stroke, TIA, any acute coronary syndrome within 6 months prior to randomization.
* Clinically relevant hepatic dysfunction at the screening visit indicated by at least one of the following:
* hepatic insufficiency (Child-Pugh B or C) as documented in medical history
* total bilirubin \> 2 times the upper limit normal (ULN) and
* alanine amino transferase (ALT) \> 3 times the ULN or
* glutamate dehydrogenase (GLDH) \> 3 times the ULN or
* gamma glutamyl transpeptidase (GGT) \> 5 times the ULN.
* Systolic blood pressure below 100 or above 160 mm Hg at the screening visit based on the average of 3 readings taken from the arm with the highest recordings.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to 20 days
measure: Number of participants with serious adverse events
timeFrame: Up to 20 days
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen Ø
country: Denmark
city: Copenhagen
country: Denmark
city: Hellerup
country: Denmark
city: Herlev
country: Denmark
city: Frankfurt
country: Germany
state: Hessen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Erfurt
country: Germany
state: Thüringen
city: Berlin
country: Germany
city: Bergamo
country: Italy
state: Lombardia
city: Brescia
country: Italy
state: Lombardia
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: