Safety and Efficacy Study of Once and Twice Daily Doses of MCC-135 in Subjects With Congestive Heart Failure.

Sponsor

Takeda (Industry)

Overall Status

Completed

CT.gov ID

NCT00050076

Collaborator

(none)

204

Enrollment

Locations

Arms

Duration (Months)

3.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effect of two different doses of MCC-135, once daily (QD) or twice daily (BID), on the disease state and the quality of life in subjects with congestive heart failure.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure	Drug: MCC-135 Drug: MCC-135 Drug: MCC-135 Drug: Placebo	Phase 2

Detailed Description

In recent years the usefulness of angiotensin converting enzyme inhibitors and vasodilators as well as beta-blockers has been realized in the treatment of heart failure. Multi-center studies clinical trials have shown some benefit of angiotensin converting enzyme inhibitors on the morbidity and mortality of heart failure subjects, and physicians are also prescribing angiotensin converting enzyme inhibitors for the initial treatment of subjects with left ventricular dysfunction. Some subjects do not respond to angiotensin converting enzyme inhibitors and intolerance to these compounds has also been observed. Despite the significant reduction in mortality observed in limited controlled studies, the 5-year mortality of subjects with congestive heart failure continues to be high, indicating that there is a significant therapeutic gap in the treatment of this disease.

MCC-135 is being studied to assess its usefulness as a supplement or replacement to current treatment and to provide subjects with specific and predictable therapy that will reverse the remodeling of the diseased heart and markedly improve the subject's survival. The current study is an exploratory clinical trial to determine the efficacy of two doses and two dose regimens of MCC-135 when compared to placebo by evaluating improvement in the subject's plasma b-type (brain) natriuretic peptide levels, regular rate (heart rate) variability and clinical signs and symptoms.

Study Design

Study Type:

Interventional

Actual Enrollment :

204 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase II, Double-Blind, Randomized, Exploratory, Placebo-Controlled Study of Efficacy, Safety, and Tolerability of MCC-135 Comparing QD vs BID Doses in Subjects With Congestive Heart Failure, NYHA Class II/III

Study Start Date :

Aug 1, 2002

Actual Primary Completion Date :

Aug 1, 2003

Actual Study Completion Date :

Aug 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MCC-135 50 mg BID	Drug: MCC-135 MCC-135 50 mg, tablets, orally, twice daily for up to 12 weeks
Experimental: MCC-135 100 mg QD	Drug: MCC-135 MCC-135 100 mg, tablets, orally, once daily for up to 12 weeks
Experimental: MCC-135 200 mg QD	Drug: MCC-135 MCC-135 200 mg, tablets, orally, once daily for up to 12 weeks
Placebo Comparator: Placebo	Drug: Placebo MCC-135 placebo-matching tablets, orally, once daily for up to 12 weeks

Outcome Measures

Primary Outcome Measures

Change from baseline in the serum levels of brain natriuretic peptide [At Final Visit.]

Secondary Outcome Measures

Change from baseline in the Minnesota living with heart failure questionnaire score [At Final Visit.]
Regular rate (heart rate) variability as measured by 24-hour Holter monitoring [At Final Visit.]
Disease progression status measured by New York Heart Association class [At Final Visit.]
Disease progression status measured by Global Clinical Status [At Final Visit.]
Disease progression status measured by Clinical Composite [At Final Visit.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion:

Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
Having a clinical diagnosis consistent with congestive heart failure, of at least 6 months duration and clinically stable for the last month.
Has a left ventricular ejection fraction less than or equal to 40%.
Has Plasma b-type (brain) natriuretic peptide levels greater than or equal to 200 pg/ml at screening.
Meeting the following requirements for current concomitant medication:
Must be using an angiotensin converting enzyme inhibitor or Angiotensin II receptor antagonists therapy for at least 1 month prior to the screening visit.
If using beta-blockers, must have commenced treatment at least 4 months prior to the screening visit.
All other cardiac medications must have been introduced at least one month prior to the screening visit.

Exclusion:

Heart failure primarily due to:
Obstructive valvular disease
Malfunctioning artificial heart valve
Congenital heart disease
Pericardial disease
Uncontrolled thyroid disease
Amyloidosis
Severe pulmonary disease
Restrictive or obstructive cardiomyopathy
Known active myocarditis
Terminal heart failure or on waiting list for transplant.
Atrio-ventricular block except for first-degree atrio-ventricular block.
A history of or currently sustained ventricular tachycardia.
Subjects with atrial fibrillation and/or requiring pacemakers (including bi-ventricular pacing).
Presence of pulmonary embolism.
Acute myocardial infarction, unstable angina, coronary revascularization or major surgery during the last 6 weeks prior to screening.
Episode of syncope or cardiac arrest during the last 6 weeks prior to screening.
Requiring treatment with the following therapies:
Anti-arrhythmics (Amiodarone/beta-blockers are permitted)
Calcium sensitizers
Catecholamines
Phosphodiesterase inhibitors
Is currently participating in another investigational study or who have participated in an investigational study (including MCC-135) during the 2 months prior to the screening visit
Has a history of drug or alcohol abuse, as defined by Diagnostic and Statistical Manual of Mental Disorders-4th edition criteria, within the past two years.
Has significant, moderate-severe renal dysfunction or disease, confirmed by serum creatinine of greater than 2mg/dl (180 micromol/L).
Serum potassium levels at entry confirmed below 3.5mmol/L.
Known severe symptomatic primary pulmonary disease in the last 5 years e.g. asthma, chronic obstructive pulmonary disease.
Concurrent severe disease (including significant hepatic, metabolic or other systemic disease) or any medical condition that, in the opinion of the investigator, would compromise the subject's safety or their successful participation in the study.
History of multiple drug allergies or with a known allergy to the study drug or any medicine chemically related to the study drug.
Individuals who are morbidly obese.
Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
Anti-arrhythmics (Amiodarone/beta-blockers are permitted)
Calcium sensitizers
Catecholamines
Phosphodiesterase inhibitors

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maricopa Medical Center	Phoenix	Arizona	United States	85008
2	University of Arizona Medical Center	Tucson	Arizona	United States	85724
3	Capitol Intervention Cardiology	Carmichael	California	United States	95608
4	San Diego Cardiovascular	Encinitas	California	United States	92024
5	LAC & USC Medical Center	Los Angeles	California	United States	90033
6	ARI Clinical Trials, Inc Arrhythmia Research & Cardiology Health Center	Redondo Beach	California	United States	90027
7	Clinical Trials Research	Roseville	California	United States	95661
8	Sacramento Heart & Vascular Medical Associates	Sacramento	California	United States	95825
9	University of California San Diego	San Diego	California	United States	92103
10	Apex Research Institute	Santa Ana	California	United States	92705
11	Cardiology Consultants PA	Daytona Beach	Florida	United States	32114
12	Cardiology Associates of Fort Lauderdale	Fort Lauderdale	Florida	United States	33308
13	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
14	Cardiovascular Center of Sarasota	Sarasota	Florida	United States	34239
15	Southern Clinical Research & Management	Augusta	Georgia	United States	30904
16	Medical Group of Fort Wayne, PC	Fort Wayne	Indiana	United States	46804
17	Medical Center Cardiologist	Louisville	Kentucky	United States	40202
18	Louisville Cardiology Medical Group, PSC	Louisville	Kentucky	United States	40207
19	Louisiana Heart Center	Chalmette	Louisiana	United States	70043
20	New Orleans Center for Clinical Research	New Orleans	Louisiana	United States	70119
21	Ochsner Clinic	New Orleans	Louisiana	United States	70121
22	Cardiac Center of Louisiana, LLC	Shreveport	Louisiana	United States	71103
23	Cardiology Associates, PC	Annapolis	Maryland	United States	21114
24	University of Maryland Hospital	Baltimore	Maryland	United States	21201
25	Cardiovascular Consultants, PA	Takoma Park	Maryland	United States	20901
26	University of Massachusettes	Worcester	Massachusetts	United States	01655
27	University of Michigan	Ann Arbor	Michigan	United States	48109
28	Henry Ford Health System	Detroit	Michigan	United States	48202
29	Henry Ford Hospital	Detroit	Michigan	United States	48202
30	Bryan LGH Heart Institute	Lincoln	Nebraska	United States	68510
31	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
32		Millburn	New Jersey	United States	07041
33	South Jersey Heart Group	Sewell	New Jersey	United States	08080
34	Albert Einstein College of Medicine	Bronx	New York	United States	10461
35	Buffalo General Hospital	Buffalo	New York	United States	14203
36	Heart Care Center East	Fayetteville	New York	United States	13066
37	Hudson Valley Clinical Research	Kingston	New York	United States	12401
38	Saint Vincent Catholic Medical Center	New York	New York	United States	10011
39	University of Rochester	Rochester	New York	United States	14618
40	Sterling Research Group	Cincinnati	Ohio	United States	45219
41	North Ohio Research, Ltd.	Lorain	Ohio	United States	44053
42	City Cardiology Associates, Inc.	Stow	Ohio	United States	44224
43	Chestnut Hill Cardiology, Ltd.	Flourtown	Pennsylvania	United States	19031
44	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
45	Medical University of South Carolina	Charleston	South Carolina	United States	29425
46	Carolina Research Associates	Columbia	South Carolina	United States	29206
47	The Stern Cardiovascular Center	Memphis	Tennessee	United States	38120
48	Cardiovascular Research Institute of Dallas Medical Center - Cardiologist Research Foundation	Dallas	Texas	United States	75231
49	Med-Tech Research	Houston	Texas	United States	77055
50		Nassau Bay	Texas	United States	77058
51	Tyler Cardiovascular Consultants	Tyler	Texas	United States	75701
52	Cardiovascular Associates, Ltd.	Chesapeake	Virginia	United States	23320
53	Wisconsin Center for Clinical Research, LLC	Elkhorn	Wisconsin	United States	53121