ARTS-HF Japan: Phase IIb Safety and Efficacy Study of BAY94-8862 in Subjects With Worsening Chronic Heart Failure and Left Ventricular Systolic Dysfunction and Either Type 2 Diabetes Mellitus With or Without Chronic Kidney Disease or Moderate Chronic Kidney Disease Alone

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT01955694

Collaborator

(none)

Enrollment

Locations

Arms

15.3

Actual Duration (Months)

2.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will be conducted in subjects with clinical diagnosis of worsening chronic heart failure and either type 2 diabetes mellitus (DM) with or without chronic kidney disease (CKD) or moderate CKD alone treated with evidence-based therapy for heart failure (HF) for at least 3 months prior to emergency presentation to hospital using a multi-center, randomized, adaptive, double-blind, double-dummy, comparator-controlled, parallel-group design.

Primary objective of the study is to investigate efficacy [percentage of subjects with a relative decrease in N-terminal prohormone B-type natriuretic peptide (NT-proBNP) of more than 30% from baseline to Visit 10 (Day 90)] and safety of different oral doses of BAY94-8862 given once daily.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: BAY94-8862 Drug: Eplerenone Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Double-dummy, Multi-center Study to Assess Safety and Efficacy of BAY94-8862 in Japanese Subjects With Emergency Presentation at the Hospital Because of Worsening Chronic Heart Failure With Left Ventricular Systolic Dysfunction and Either Type 2 Diabetes Mellitus With or Without Chronic Kidney Disease or Moderate Chronic Kidney Disease Alone Versus Eplerenone

Actual Study Start Date :

Nov 11, 2013

Actual Primary Completion Date :

Jan 23, 2015

Actual Study Completion Date :

Feb 20, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BAY94-8862 (2.5 mg) 2.5 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 5 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium	Drug: BAY94-8862 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets Drug: Placebo matching placebo
Experimental: BAY94-8862 (5 mg) 5 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 10 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium	Drug: BAY94-8862 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets Drug: Placebo matching placebo
Active Comparator: Eplerenone 25 mg eplerenone every other day, i.e. one 25 mg eplerenone capsule on Day 1, Day 3, Day 5, etc. in the morning, 1 placebo capsule on Day 2, Day 4, Day 6, etc. in the morning, and 1 placebo tablet once daily in the morning, with possible up-titration to 25 mg eplerenone once daily at Visit 6 (Day 30), i.e. one 25 mg eplerenone capsule once daily in the morning and 1 placebo tablet once daily in the morning, and a possible up-titration to 25 mg once daily [if not performed at Visit 6 (Day 30)] or to 50 mg once daily [if up-titrated to 25 mg once daily at Visit 6 (Day 30)] at Visit 8 (Day 60), based on the value of blood potassium	Drug: Eplerenone INSPRA 25 and 50 mg tablets (MAH: Pfizer) will be used for eplerenone 25 and 50 mg tablets Drug: Placebo matching placebo
Experimental: BAY94-8862 (7.5 mg) 7.5 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 15 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium Note: This treatment group may be introduced into the study or not after safety and tolerability of these doses has been assessed by an independent Data Monitoring Committee (DMC) (1st dose recommendation DMC meeting).	Drug: BAY94-8862 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets Drug: Placebo matching placebo
Experimental: BAY94-8862 (10 mg) 10 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 20 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium Note: Only in case the above mentioned additional treatment arm (BAY94-8862, 7.5 mg) has been added, a second dose decision meeting of the DMC will take place, Again safety and tolerability of all doses will be assessed by an independent DMC (2nd dose recommendation DMC meeting). Based on this data, none or up to two treatment groups (BAY94-8862, 10 mg and BAY94-8862,15 mg) may be introduced into the study.	Drug: BAY94-8862 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets Drug: Placebo matching placebo
Experimental: BAY94-8862 (15 mg) 15 mg BAY94-8862 tablet and placebo capsule once daily in the morning, with possible up-titration to 20 mg once daily at Visit 6 (Day 30), and sham up-titration at Visit 8 (Day 60), based on the value of blood potassium Note: Only in case the above mentioned additional treatment arm (BAY94-8862, 7.5 mg) has been added, a second dose decision meeting of the DMC will take place, Again safety and tolerability of all doses will be assessed by an independent DMC (2nd dose recommendation DMC meeting). Based on this data, none or up to two treatment groups (BAY94-8862, 10 mg and BAY94-8862,15 mg) may be introduced into the study.	Drug: BAY94-8862 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg of BAY94-8862 tablets Drug: Placebo matching placebo

Outcome Measures

Primary Outcome Measures

The percentage of subjects with a relative decrease in N-terminal prohormone B-type natriuretic peptide of more than 30% from baseline to Visit 10 [From baseline to 90 days]

Secondary Outcome Measures

Change in serum potassium [From baseline to 90 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects with worsening chronic heart failure requiring emergency presentation to hospital and treatment with intravenous (IV) diuretics at hospital
Subjects with either type 2 DM or moderate CKD

Exclusion Criteria:

Acute de-novo heart failure or acute inflammatory heart disease, e.g. acute myocarditis
Acute coronary syndrome (ACS) (elevated cardiac troponins which are not caused by an ACS are not an exclusion criterion) in the last 30 days prior to the screening visit
Cardiogenic shock
Valvular heart disease requiring surgical intervention during the course of the study
Subjects with left ventricular assistance device or waiting for heart transplantation
Stroke or transient ischemic cerebral attack in the last 3 months prior to the screening visit
Addison's disease

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Seto	Aichi	Japan	489-8642
2	Toyota	Aichi	Japan	471-8513
3	Funabashi	Chiba	Japan	273-8588
4	Kamogawa	Chiba	Japan	296-8602
5	Matsuyama	Ehime	Japan	790-0067
6	Chikushino	Fukuoka	Japan	818-8516
7	Amagasaki	Hyogo	Japan	660-8550
8	Kobe	Hyogo	Japan	650-0047
9	Kobe	Hyogo	Japan	654-0155
10	Higashiibaraki	Ibaraki	Japan	311-3193
11	Hiratsuka	Kanagawa	Japan	254-8502
12	Kawasaki	Kanagawa	Japan	211-8533
13	Yokohama	Kanagawa	Japan	245-8575
14	Uji	Kyoto	Japan	611-0041
15	Sendai	Miyagi	Japan	983-8520
16	Naha	Okinawa	Japan	900-0005
17	Naha	Okinawa	Japan	902-8511
18	Urasoe	Okinawa	Japan	901-2132
19	Sayama	Saitama	Japan	350-1305
20	Kusatsu	Shiga	Japan	525-8585
21	Shinjuku-ku	Tokyo	Japan	162-8655
22	Shinjuku-ku	Tokyo	Japan	162-8666
23	Kofu	Yamanashi	Japan	400-8506
24	Fukuoka		Japan	810-0001
25	Kagoshima		Japan	892-0853
26	Kyoto		Japan	607-8062
27	Okayama		Japan	700-8607
28	Osaka		Japan	558-8558
29	Shizuoka		Japan	420-8630