BAY94-8862 Dose Finding Trial in Subjects With Chronic Heart Failure and Mild (Part A) or Moderate (Part B) Chronic Kidney Disease (ARTS)

A Randomized, Double-blind, Multi-center Study to Assess Safety and Tolerability of Different Oral Doses of BAY94-8862 in Subjects With Stable Chronic Heart Failure With Left Ventricular Systolic Dysfunction and Mild (Part A) or Moderate (Part B) Chronic Kidney Disease Versus Placebo (Part A) or Versus Placebo and Spironolactone (Part B)

A placebo (Part A) and placebo and active comparator controlled (Part B), double-blind and randomized study to assess safety and tolerability of a new drug (BAY94-8862) given orally

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: BAY94-8862; Drug: BAY94-8862; Drug: BAY94-8862; Drug: BAY94-8862; Drug: Placebo; Drug: Spironolactone

• Study Type: Interventional
• Enrollment (Actual): 457
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1100
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4010
  • Steiermark
    • Graz, Steiermark, Austria, 8036
• Belgium
  • Brasschaat, Belgium, 2930
  • Bruxelles - Brussel, Belgium, 1200
  • Roeselare, Belgium, 8800
• Czechia
  • Brno, Czechia, 625 00
  • Liberec, Czechia, 460 63
  • Praha 2, Czechia, 12808
  • Praha 5, Czechia, 15030
• Denmark
  • Copenhagen Ø, Denmark, 2100
  • Esbjerg, Denmark, 6700
  • Frederiksberg, Denmark, 2000
  • Hellerup, Denmark, 2900
  • Herlev, Denmark, 2730
  • Hvidovre, Denmark, 2650
  • København NV, Denmark, 2400
  • Køge, Denmark, 4600
  • Odense, Denmark, 5000
  • Svendborg, Denmark, 5700
  • Viborg, Denmark, 8800
• Finland
  • Helsinki, Finland, FIN-00260
  • Jyväskylä, Finland, FI-40620
  • Turku, Finland, FIN-20520
• Germany
  • Berlin, Germany, 13353
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50968
  • Sachsen
    • Dresden, Sachsen, Germany, 01277
    • Wermsdorf, Sachsen, Germany, 04779
  • Schleswig-Holstein
    • Wedel, Schleswig-Holstein, Germany, 22880
  • Thüringen
    • Erfurt, Thüringen, Germany, 99084
• Israel
  • Afula, Israel, 1834111
  • Ashkelon, Israel, 7830604
  • Hadera, Israel, 3810101
  • Petah Tikva, Israel, 4941492
  • Rehovot, Israel, 7610001
  • Tel Aviv, Israel, 64239
  • Zefat, Israel, 1311001
• Norway
  • Oslo, Norway, 0450
  • Stavanger, Norway
• Poland
  • Krakow, Poland, 30-082
  • Piotrkow Trybunalski, Poland, 97-635
  • Szczecin, Poland, 70-965
  • Warszawa, Poland, 04-635
  • Wroclaw, Poland, 50-981
• Sweden
  • Kristianstad, Sweden, 29185
  • Lund, Sweden, 222 21
  • Stockholm, Sweden
  • Stockholm, Sweden, 118 83
  • Stockholm, Sweden, 111 35

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men aged 18 years and older or postmenopausal women aged 55 years and older or women aged 18 years and older without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy
• Clinical diagnosis of CHF (chronic heart failure), either ischemic or non-ischemic, NYHA (New York Heart Association) class II - III, treated with evidenced-based therapy for CHF, e.g. beta-blockers and ACE (angiotensin-converting enzyme) inhibitors or ARB (angiotensin receptor blocker) as well as diuretics, unless contraindicated or not tolerated

• Known kidney damage for >/= 3 months, as defined by structural or functional abnormalities of the kidney, and

  • Part A: 60 mL/min/1.73 m*2 </= eGFR (estimated Glomerular Filtration Rate) < 90 mL/min/1.73 m*2 (MDRD, Modification of Diet in Renal Disease) at the screening visit
  • Part B: 30 mL/min/1.73 m*2 </= eGFR <= 60 mL/min/1.73 m*2 (MDRD) at the screening visit
• Serum potassium </= 4.8 mmol/L at the screening visit
• Systolic blood pressure >/= 90 mmHg without signs or symptoms of hypotension at the screening visit

Exclusion Criteria:

• Known hypersensitivity to the study drug (active substance or excipients) or spironolactone and respective excipients (Part B only)
• Subjects with anuria, acute renal failure, or Addison's disease
• Acute coronary syndrome or unstable coronary artery disease within 30 days prior to randomization
• Valvular heart disease requiring surgical intervention during the course of the study
• History of hospitalization for hyperkalemia or acute renal failure induced by previous aldosterone antagonist treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1	Drug: BAY94-8862; Two 1.25 mg BAY94-8862 and 2 placebo tablets for duration of 4 weeks; Drug: BAY94-8862; Four 1.25 mg BAY94-8862 tablets for duration of 4 weeks; Drug: BAY94-8862; One 10 mg BAY94-8862 tablet for duration of 4 weeks; Drug: BAY94-8862; Part B only: Four 1.25 mg BAY94-8862 tablets in the morning and four tablets in the evening for duration of 4 weeks
EXPERIMENTAL: Arm 2	Drug: BAY94-8862; Two 1.25 mg BAY94-8862 and 2 placebo tablets for duration of 4 weeks; Drug: BAY94-8862; Four 1.25 mg BAY94-8862 tablets for duration of 4 weeks; Drug: BAY94-8862; One 10 mg BAY94-8862 tablet for duration of 4 weeks; Drug: BAY94-8862; Part B only: Four 1.25 mg BAY94-8862 tablets in the morning and four tablets in the evening for duration of 4 weeks
EXPERIMENTAL: Arm 3	Drug: BAY94-8862; Two 1.25 mg BAY94-8862 and 2 placebo tablets for duration of 4 weeks; Drug: BAY94-8862; Four 1.25 mg BAY94-8862 tablets for duration of 4 weeks; Drug: BAY94-8862; One 10 mg BAY94-8862 tablet for duration of 4 weeks; Drug: BAY94-8862; Part B only: Four 1.25 mg BAY94-8862 tablets in the morning and four tablets in the evening for duration of 4 weeks
EXPERIMENTAL: Arm 4	Drug: BAY94-8862; Two 1.25 mg BAY94-8862 and 2 placebo tablets for duration of 4 weeks; Drug: BAY94-8862; Four 1.25 mg BAY94-8862 tablets for duration of 4 weeks; Drug: BAY94-8862; One 10 mg BAY94-8862 tablet for duration of 4 weeks; Drug: BAY94-8862; Part B only: Four 1.25 mg BAY94-8862 tablets in the morning and four tablets in the evening for duration of 4 weeks
PLACEBO_COMPARATOR: Arm 5	Drug: Placebo; Placebo tablets for duration of 4 weeks
ACTIVE_COMPARATOR: Arm 6	Drug: Spironolactone; Part B only: 25 mg spironolactone once daily with up-titration to 50 mg once daily starting at day 15, if serum potassium is less or equal to 4.8 mmol/L, for duration of 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of serum potassium	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in serum magnesium	Day 8, Day 15, Day 22, Day 29
Change in blood pressure	Day 8, Day 15, Day 22, Day 29
Change in heart rate	Day 8, Day 15, Day 22, Day 29

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.
• Pitt B, Filippatos G, Gheorghiade M, Kober L, Krum H, Ponikowski P, Nowack C, Kolkhof P, Kim SY, Zannad F. Rationale and design of ARTS: a randomized, double-blind study of BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease. Eur J Heart Fail. 2012 Jun;14(6):668-75. doi: 10.1093/eurjhf/hfs061. Epub 2012 May 4.
• Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, Nowack C, Kolkhof P, Kim SY, Zannad F. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013 Aug;34(31):2453-63. doi: 10.1093/eurheartj/eht187. Epub 2013 May 27.

Helpful Links

• Click here to find results for studies related to Bayer products
• Click here to find information about studies related to Bayer products conducted in Europe

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 9, 2011
• Primary Completion (ACTUAL): May 30, 2012
• Study Completion (ACTUAL): July 16, 2012

Study Registration Dates

• First Submitted: April 29, 2011
• First Submitted That Met QC Criteria: April 29, 2011
• First Posted (ESTIMATE): May 2, 2011

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2022
• Last Update Submitted That Met QC Criteria: January 27, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Chronic Heart Failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Urologic Diseases; Renal Insufficiency; Heart Failure; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: 14563; 2011-000301-45 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.