Clinical trial NCT02452515 (phase 2, status: completed)
Conditions: heart failure
ICD codes: I50.814, I09.81, I50.82, I50.89, I50.9, T86.22, I11.0
Drugs: bay1142524, bay1142524, bay1142524, bay1142524, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
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.