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

Congestive Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00050076
• Other study ID #: 01-02-TL-MCC135-001
• Secondary ID: U1111-1127-6077
• Status: Completed
• Phase: Phase 2
• First received: November 20, 2002
• Last updated: January 31, 2012
• Start date: August 2002
• Est. completion date: August 2003

Study information

• Verified date: January 2012
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 204
• Est. completion date: August 2003
• Est. primary completion date: August 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• MCC-135
MCC-135 50 mg, tablets, orally, twice daily for up to 12 weeks
• MCC-135
MCC-135 100 mg, tablets, orally, once daily for up to 12 weeks
• MCC-135
MCC-135 200 mg, tablets, orally, once daily for up to 12 weeks
• Placebo
MCC-135 placebo-matching tablets, orally, once daily for up to 12 weeks

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Cardiology Associates, PC	Annapolis	Maryland
United States	Southern Clinical Research & Management	Augusta	Georgia
United States	University of Maryland Hospital	Baltimore	Maryland
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Buffalo General Hospital	Buffalo	New York
United States	Capitol Intervention Cardiology	Carmichael	California
United States	Louisiana Heart Center	Chalmette	Louisiana
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cardiovascular Associates, Ltd.	Chesapeake	Virginia
United States	Sterling Research Group	Cincinnati	Ohio
United States	Carolina Research Associates	Columbia	South Carolina
United States	Cardiovascular Research Institute of Dallas Medical Center - Cardiologist Research Foundation	Dallas	Texas
United States	Cardiology Consultants PA	Daytona Beach	Florida
United States	Henry Ford Health System	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wisconsin Center for Clinical Research, LLC	Elkhorn	Wisconsin
United States	San Diego Cardiovascular	Encinitas	California
United States	Heart Care Center East	Fayetteville	New York
United States	Chestnut Hill Cardiology, Ltd.	Flourtown	Pennsylvania
United States	Cardiology Associates of Fort Lauderdale	Fort Lauderdale	Florida
United States	Medical Group of Fort Wayne, PC	Fort Wayne	Indiana
United States	Med-Tech Research	Houston	Texas
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Hudson Valley Clinical Research	Kingston	New York
United States	Bryan LGH Heart Institute	Lincoln	Nebraska
United States	North Ohio Research, Ltd.	Lorain	Ohio
United States	LAC & USC Medical Center	Los Angeles	California
United States	Louisville Cardiology Medical Group, PSC	Louisville	Kentucky
United States	Medical Center Cardiologist	Louisville	Kentucky
United States	The Stern Cardiovascular Center	Memphis	Tennessee
United States	New Orleans Center for Clinical Research	New Orleans	Louisiana
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Saint Vincent Catholic Medical Center	New York	New York
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Maricopa Medical Center	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	ARI Clinical Trials, Inc Arrhythmia Research & Cardiology Health Center	Redondo Beach	California
United States	University of Rochester	Rochester	New York
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	Cardiovascular Center of Sarasota	Sarasota	Florida
United States	South Jersey Heart Group	Sewell	New Jersey
United States	Cardiac Center of Louisiana, LLC	Shreveport	Louisiana
United States	City Cardiology Associates, Inc.	Stow	Ohio
United States	Cardiovascular Consultants, PA	Takoma Park	Maryland
United States	University of Arizona Medical Center	Tucson	Arizona
United States	Tyler Cardiovascular Consultants	Tyler	Texas
United States	University of Massachusettes	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the serum levels of brain natriuretic peptide		At Final Visit.	No
Secondary	Change from baseline in the Minnesota living with heart failure questionnaire score		At Final Visit.	No
Secondary	Regular rate (heart rate) variability as measured by 24-hour Holter monitoring		At Final Visit.	No
Secondary	Disease progression status measured by New York Heart Association class		At Final Visit.	No
Secondary	Disease progression status measured by Global Clinical Status		At Final Visit.	No
Secondary	Disease progression status measured by Clinical Composite		At Final Visit.	No