A study to investigate the safety and tolerability of a 14 day oral treatment with different doses of BAY 1142524 in comparison to placebo in patients with left-ventricular dysfunction after myocardial infarction.

• Register: EUCTR
• Last refreshed on: 13 June 2016
• Main ID: EUCTR2014-005297-12-DK
• Date of registration: 11/05/2015
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: A study to investigate the safety and tolerability of a 14 day oral treatment with different doses of BAY 1142524 in comparison to placebo in patients with left-ventricular dysfunction after myocardial infarction.
• Scientific 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 BAY 1142524 in comparison to placebo in clinically stable patients with left-ventricular dysfunction after myocardial infarction
• Date of first enrolment: 29/05/2015
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005297-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 8
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Denmark, Germany, Italy

Contacts

• Name: Early Clinical Lead (ECL)
• Affiliation: Bayer HealthCare AG

• Name: Early Clinical Lead (ECL)
• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Clinically stable patients with left-ventricular dysfunction (LVEF = 45%) after myocardial infarction, whereby the MI occurred 6 or more months before randomization.
2. NYHA class I-II.
3. 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.
4. 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 ACE inhibitor or an ARB. Beta-blockers, diuretics, 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 ESC guidelines, see appendix 16.4) = 4 weeks prior to the screening visit is mandatory.
5. No planned changes to post MI drug therapy during the active treatment phase of the study.
6. Men or confirmed postmenopausal women (defined as exhibiting spontaneous amenorrhea for at least 12 months before screening or as exhibiting spontaneous amenorrhea for 6 months before screening with documented serum FSH levels > 40 mIU/mL) or women without childbearing potential based on surgical treatment 6 weeks before screening such as bilateral tubal ligation, bilateral oophorectomy with or without 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.
7. Age: 40 to 79 years (inclusive) at the screening visit.
8. Race: Caucasian
9. Ability to understand and follow study-related instructions.
10. Written informed consent. The informed consent must be signed before any study specific tests or procedures are done.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion criteria:
Medical and surgical history
1. 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).
2. Hospitalization for decompensated heart failure within the last 3 months prior to randomization.
3. Coronary revascularization within 6 weeks prior to randomization or if revascularization is anticipated or needed during the study duration.
4. Clinically relevant, (i.e. requiring revascularization [such as coronary artery bypass grafting or percutaneous coronary intervention]) cardiac ischemia in a stress test within 3 months before screening.
5. Previous assignment to treatment during this study.
6. Any planned intervention such as: implantation of an implantable cardioverter defibrillator, implantation of cardiac resynchronization therapy devices or implantation of left ventricular assist devices, bypass operation, listing for heart transplantation or any other planned operations and medical interventions.
7. Patients carrying implantable cardioverter defibrillators, cardiac resynchronistaion therapy devices or left ventricular assist devices that had events such as ventricular tachycardias, ventricular fibrillation in the last 6 months before randomization while carrying the devices
8. Primary and uncorrected valvular disease with foreseen requirement of valve repair within the next 6 months.
9. Any stroke, TIA, any acute coronary syndrome within 6 months prior to randomization.
10. Clinically relevant hepatic dysfunction at the screening visit indicated by at least one of the following:
o hepatic insufficiency (Child-Pugh B or C) as documented in medical history
o 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 (?GT) > 5 times the ULN.
11. Known hypersensitivity to the study drugs (active substances or excipients of the preparations).
12. Patients suffering from any autoimmune disease.
13. Medical condition or history thereof that in the opinion of the investigator would impair the ability to complete the planned study procedures.
14. Anemia as evidenced by hemoglobin values of = 10 mg/dl at screening.
15. Hyperthyreosis or hypothyreosis as evidenced by TSH values outside the reference range at screening.
16. Any deviation from normal laboratory values that in the opinion of the investigator would impair the ability to complete the planned study procedures or pose a potential safety risk.
Medication, drug use and special behavioral patterns
17. Use of antacids containing hydroxide salts during the study conduct. Patients using hydroxide salt containing antacid should be switched to proton pump inhibitors at least one week before treatment with study drug (day 0).
18. Consumption of grapefruit juice or St. John’s wort during the study conduct and two weeks before starting the clinical phase of the study.
19. Medication with CYP3A4 inhibitors (amiodarone, dronedarone, diltiazem, verapamil, fluvoxamine, nefazodone, clarithromycin, and antimycotics such as fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole) within 4 weeks before screening and during the study.
20. Suspicion of drug or alcohol abuse (defined as more than 24 g of pure alcoho

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

left-ventricular dysfunction after myocardial infarction
MedDRA version: 19.0 Level: PT Classification code 10049694 Term: Left ventricular dysfunction System Organ Class: 10007541 - Cardiac disorders
MedDRA version: 19.0 Level: LLT Classification code 10028598 Term: Myocardial infarction old System Organ Class: 10007541 - Cardiac disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: BAY 1142524 5 mg tablets
Product Code: BAY 1142524
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not yet assigned
Current Sponsor code: BAY 1142524
Other descriptive name: BAY 1142524
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: BAY 1142524 50 mg Film-coated tablets
Product Code: BAY 1142524
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not yet assigned
Current Sponsor code: BAY 1142524
Other descriptive name: BAY 1142524
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: An additional objective is to assess the pharmacokinetics of BAY 1142524 in plasma after multiple doses and to explore the effects of BAY 1142524 on neuro-hormonal and immunological biomarkers in stable patients with LVD

Timepoint(s) of evaluation of this end point: As described in protocol 9.6

Main Objective: The primary objective of this pilot study is to investigate the safety and tolerability after multiple oral doses of BAY 1142524 administered BID (using 3 dose groups) or OD (using a 4th dose group) as combinations of 5 and 50 mg IR tablets for 14 days in 12 patients with left-ventricular dysfunction after myocardial infarction (9 verum and 3 placebo) per dose group in comparison to placebo in a randomized, single blind group-comparison design.

Primary end point(s): Safety as evidenced by the incidence and severity of adverse events and potential hemodynamic effects

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: NA

Secondary end point(s): NA

Secondary ID(s)

2014-005297-12-DE

BAY1142524/17055

Source(s) of Monetary Support

Bayer HealthCare AG