A Single-blind Pilot Study to Investigate Safety and Tolerability of the Chymase Inhibitor BAY1142524 in Clinically Stable Patients With Left-ventricular Dysfunction (CHIARA MIA 1)

• ClinicalTrials.gov Identifier: NCT02452515
• Recruitment Status: Completed
• First Posted: May 22, 2015
• Last Update Posted: November 7, 2017
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: May 20, 2015
• First Posted Date: May 22, 2015
• Last Update Posted Date: November 7, 2017
• Study Start Date: July 2015
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2015)

• Number of participants with adverse events [ Time Frame: Up to 20 days ]
• Number of participants with serious adverse events [ Time Frame: Up to 20 days ]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Other
• Condition: Heart Failure

Intervention

• Drug: BAY1142524
  5 mg BAY1142524 or placebo given as 5 mg IR tablet twice daily for 2 weeks
• Drug: BAY1142524
  10 mg BAY1142524 or placebo given as 2 x 5 mg IR tablets twice daily as for 2 weeks
• Drug: BAY1142524
  25 mg BAY1142524 or placebo given as 5 x 5 mg IR tablets twice daily for 2 weeks
• Drug: BAY1142524
  50 mg BAY1142524 or placebo given 1 x 50 mg IR tablet once daily for 2 weeks
• Drug: Placebo
  The patients will be treated orally with combinations of IR tablets containing placebo to achieve the indicated dosages.

Study Arms

• Experimental: BAY1142524 (5 mg)
  12 patients with left-ventricular dysfunction after myocardial infarction, 9 patients allocated to verum treatment, 3 patients allocated to placebo treatment
  Interventions:

  • Drug: BAY1142524
  • Drug: Placebo
• Experimental: BAY1142524 (10 mg)
  12 patients with left-ventricular dysfunction after myocardial infarction, 9 patients allocated to verum treatment, 3 patients allocated to placebo treatment
  Interventions:

  • Drug: BAY1142524
  • Drug: Placebo
• Experimental: BAY1142524 (25 mg)
  12 patients with left-ventricular dysfunction after myocardial infarction, 9 patients allocated to verum treatment, 3 patients allocated to placebo treatment
  Interventions:

  • Drug: BAY1142524
  • Drug: Placebo
• Experimental: BAY1142524 (50 mg)
  12 patients with left-ventricular dysfunction after myocardial infarction, 9 patients allocated to verum treatment, 3 patients allocated to placebo treatment
  Interventions:

  • Drug: BAY1142524
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 4, 2016): 49
• Original Estimated Enrollment (submitted: May 20, 2015): 48
• Actual Study Completion Date: March 2016
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 79 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Germany, Italy

Administrative Information

• NCT Number: NCT02452515
• Other Study ID Numbers: 17055; 2014-005297-12 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bayer
• Original Responsible Party: Same as current
• Current Study Sponsor: Bayer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: March 2017