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

NCT ID: NCT00050076

Last Updated: 2012-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-08-31
• Study Completion Date: 2003-08-31

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.

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.

Conditions

Congestive Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

MCC-135 50 mg BID

Group Type: EXPERIMENTAL

MCC-135

Intervention Type: DRUG

MCC-135 50 mg, tablets, orally, twice daily for up to 12 weeks

MCC-135 100 mg QD

Group Type: EXPERIMENTAL

MCC-135

Intervention Type: DRUG

MCC-135 100 mg, tablets, orally, once daily for up to 12 weeks

MCC-135 200 mg QD

Group Type: EXPERIMENTAL

MCC-135

Intervention Type: DRUG

MCC-135 200 mg, tablets, orally, once daily for up to 12 weeks

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

MCC-135 placebo-matching tablets, orally, once daily for up to 12 weeks

Interventions

MCC-135

MCC-135 50 mg, tablets, orally, twice daily for up to 12 weeks

Intervention Type: DRUG

MCC-135

MCC-135 100 mg, tablets, orally, once daily for up to 12 weeks

Intervention Type: DRUG

MCC-135

MCC-135 200 mg, tablets, orally, once daily for up to 12 weeks

Intervention Type: DRUG

Placebo

MCC-135 placebo-matching tablets, orally, once daily for up to 12 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

VP Clinical Science Strategy

Role: STUDY_DIRECTOR

Takeda

Locations

Maricopa Medical Center

Phoenix, Arizona, United States

University of Arizona Medical Center

Tucson, Arizona, United States

Capitol Intervention Cardiology

Carmichael, California, United States

San Diego Cardiovascular

Encinitas, California, United States

LAC & USC Medical Center

Los Angeles, California, United States

ARI Clinical Trials, Inc Arrhythmia Research & Cardiology Health Center

Redondo Beach, California, United States

Clinical Trials Research

Roseville, California, United States

Sacramento Heart & Vascular Medical Associates

Sacramento, California, United States

University of California San Diego

San Diego, California, United States

Apex Research Institute

Santa Ana, California, United States

Cardiology Consultants PA

Daytona Beach, Florida, United States

Cardiology Associates of Fort Lauderdale

Fort Lauderdale, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Cardiovascular Center of Sarasota

Sarasota, Florida, United States

Southern Clinical Research & Management

Augusta, Georgia, United States

Medical Group of Fort Wayne, PC

Fort Wayne, Indiana, United States

Medical Center Cardiologist

Louisville, Kentucky, United States

Louisville Cardiology Medical Group, PSC

Louisville, Kentucky, United States

Louisiana Heart Center

Chalmette, Louisiana, United States

New Orleans Center for Clinical Research

New Orleans, Louisiana, United States

Ochsner Clinic

New Orleans, Louisiana, United States

Cardiac Center of Louisiana, LLC

Shreveport, Louisiana, United States

Cardiology Associates, PC

Annapolis, Maryland, United States

University of Maryland Hospital

Baltimore, Maryland, United States

Cardiovascular Consultants, PA

Takoma Park, Maryland, United States

University of Massachusettes

Worcester, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Health System

Detroit, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Bryan LGH Heart Institute

Lincoln, Nebraska, United States

Alegent Health Immanuel Medical Center

Omaha, Nebraska, United States

Millburn, New Jersey, United States

South Jersey Heart Group

Sewell, New Jersey, United States

Buffalo General Hospital

Buffalo, New York, United States

Heart Care Center East

Fayetteville, New York, United States

Hudson Valley Clinical Research

Kingston, New York, United States

Saint Vincent Catholic Medical Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

Albert Einstein College of Medicine

The Bronx, New York, United States

Sterling Research Group

Cincinnati, Ohio, United States

North Ohio Research, Ltd.

Lorain, Ohio, United States

City Cardiology Associates, Inc.

Stow, Ohio, United States

Chestnut Hill Cardiology, Ltd.

Flourtown, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Carolina Research Associates

Columbia, South Carolina, United States

The Stern Cardiovascular Center

Memphis, Tennessee, United States

Cardiovascular Research Institute of Dallas Medical Center - Cardiologist Research Foundation

Dallas, Texas, United States

Med-Tech Research

Houston, Texas, United States

Nassau Bay, Texas, United States

Tyler Cardiovascular Consultants

Tyler, Texas, United States

Cardiovascular Associates, Ltd.

Chesapeake, Virginia, United States

Wisconsin Center for Clinical Research, LLC

Elkhorn, Wisconsin, United States

Countries

United States

Other Identifiers

U1111-1127-6077

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-02-TL-MCC135-001

Identifier Type: -

Identifier Source: org_study_id