BAY94-8862 dose finding trial in subjects with chronic heart failure and mild (Part A) or moderate (Part B) chronic kidney disease

• Register: EUCTR
• Last refreshed on: 15 July 2013
• Main ID: EUCTR2011-000301-45-DE
• Date of registration: 23/03/2011
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: BAY94-8862 dose finding trial in subjects with chronic heart failure and mild (Part A) or moderate (Part B) chronic kidney disease
• Scientific title: A randomized, double-blind, multi-center study to assess safety and tolerability of different oral doses of BAY 94-8862 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) - ARTS study
• Date of first enrolment: 12/05/2011
• Target sample size: 425
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000301-45
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Other specify the comparator: Spironolactone Number of treatment arms in the trial: 6

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Finland, Germany, Israel, Norway, Poland, Sweden

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer Healthcare AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer Healthcare AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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
2. 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
3. Known kidney damage for >/= 3 months, as defined by structural or functional abnormalities of the kidney, and
-- Part A: 60 mL/min/1.73 m2 -- Part B: 30 mL/min/1.73 m2 4. Serum potassium 5. Systolic blood pressure >/= 90 mmHg without signs or symptoms of hypotension at the screening visit

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 85
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 340

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



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

Health Condition(s) or Problem(s) studied

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

Stable chronic heart failure subjects with left ventricular systolic dysfunction and mild (Part A) or moderate (Part B) chronic kidney disease
MedDRA version: 14.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 10007541 - Cardiac disorders

Intervention(s)

Product Name: BAY 94-8862 IR tablet 1.25 mg
Product Code: BAY 94-8862 coated tablet 1.25 mg
Pharmaceutical Form: Film-coated tablet
CAS Number: 1050477-31-0
Current Sponsor code: BAY 94-8862 micronized
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: BAY 94-8862 IR tablet 10 mg
Product Code: BAY 94-8862 coated tablet 10 mg
Pharmaceutical Form: Film-coated tablet
CAS Number: 1050477-31-0
Current Sponsor code: BAY 94-8862 micronized
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Aldactone 25 mg
Product Name: Aldactone 25 mg
Pharmaceutical Form: Film-coated tablet
CAS Number: 52-01-7
Other descriptive name: SPIRONOLACTONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Secondary Objective: Secondary objectives of Part B of the study are:
To investigate the change of serum potassium after treatment with 4 oral dosages of BAY 94 8862 given once or twice daily over 4 weeks versus the active comparator spironolactone in subjects with CHF with LVSD and moderate CKD (30 mL/min/1.73 m2 =< eGFR =<60 mL/min/1.73 m2).
To assess safety and tolerability of these doses, the effect on cardiac function by changes in concentrations of various biomarkers, and the change in biomarkers of renal function, eGFR (MDRD), and albuminuria. In addition, pharmacokinetics of BAY 94 8862 and its metabolites in plasma after multiple oral doses will be assessed.

Main Objective: Part A
The safety and tolerability of 3 oral doses of BAY 94 8862 given once daily over 4 weeks in a randomized, placebo-controleld, double-blind study in subjects with chronic heart failure (CHF) with left ventricular systolic dysfunction (LVSD) and mild chronic kidney disease (CKD) (60 mL/min/7.73 m2 => eGFR <90 mL/min/1.73 m2). the effects on serum potassium, the effects of these doses on the change in biomarkers of renal function, eGFR using the Modification of Diet in Renal Disease Study Group (MDRD) formula, albuminuria, and pharmacokinetics of BAY 94 8862 and its metabolites in plasma after multiple oral doses.
Part B
To investigate the change of serum potassium after treatment with 4 oral dosages of BAY 94 8862 given once or twice daily over 4 weeks in a randomized, placebo-controlled, double-blind study design versus placebo in subjects with CHF with LVSD adn moderate CKD (30 mL/min/1.73 m2=

Timepoint(s) of evaluation of this end point: 4 weeks

Primary end point(s): Change in serum potassium

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 8, Day 15, Day 22, Day 29

Secondary end point(s): Change in serum magnesium , change in blood pressure, change in heart rate

Secondary ID(s)

BAY94-8862/14563

2011-000301-45-SE

Source(s) of Monetary Support

Bayer HealthCare AG