Overview

A Single-blind Pilot Study to Investigate Safety and Tolerability of the Chymase Inhibitor BAY1142524 in Clinically Stable Patients With Left-ventricular Dysfunction

Status:
Completed
Trial end date:
2016-03-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Bayer
Treatments:
Fulacimstat
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.