Clinical trial NCT00050076: Safety and Efficacy Study of Once and Twice Daily Doses of MCC-135 in Subjects With Congestive Heart Failure.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congestive Heart Failure
Keywords: Congestive Heart Failure
Cardiac Failure
Heart Decompensation
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2002-11-21
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in the serum levels of brain natriuretic peptide
timeFrame: At Final Visit.
Secondary outcomes:
measure: Change from baseline in the Minnesota living with heart failure questionnaire score
timeFrame: At Final Visit.
measure: Regular rate (heart rate) variability as measured by 24-hour Holter monitoring
timeFrame: At Final Visit.
measure: Disease progression status measured by New York Heart Association class
timeFrame: At Final Visit.
measure: Disease progression status measured by Global Clinical Status
timeFrame: At Final Visit.
measure: Disease progression status measured by Clinical Composite
timeFrame: At Final Visit.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Maricopa Medical Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Medical Center
state: Arizona
city: Carmichael
country: United States
facility: Capitol Intervention Cardiology
state: California
city: Encinitas
country: United States
facility: San Diego Cardiovascular
state: California
city: Los Angeles
country: United States
facility: LAC & USC Medical Center
state: California
city: Redondo Beach
country: United States
facility: ARI Clinical Trials, Inc Arrhythmia Research & Cardiology Health Center
state: California
city: Roseville
country: United States
facility: Clinical Trials Research
state: California
city: Sacramento
country: United States
facility: Sacramento Heart & Vascular Medical Associates
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Santa Ana
country: United States
facility: Apex Research Institute
state: California
city: Daytona Beach
country: United States
facility: Cardiology Consultants PA
state: Florida
city: Fort Lauderdale
country: United States
facility: Cardiology Associates of Fort Lauderdale
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Sarasota
country: United States
facility: Cardiovascular Center of Sarasota
state: Florida
city: Augusta
country: United States
facility: Southern Clinical Research & Management
state: Georgia
city: Fort Wayne
country: United States
facility: Medical Group of Fort Wayne, PC
state: Indiana
city: Louisville
country: United States
facility: Medical Center Cardiologist
state: Kentucky
city: Louisville
country: United States
facility: Louisville Cardiology Medical Group, PSC
state: Kentucky
city: Chalmette
country: United States
facility: Louisiana Heart Center
state: Louisiana
city: New Orleans
country: United States
facility: New Orleans Center for Clinical Research
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Shreveport
country: United States
facility: Cardiac Center of Louisiana, LLC
state: Louisiana
city: Annapolis
country: United States
facility: Cardiology Associates, PC
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland Hospital
state: Maryland
city: Takoma Park
country: United States
facility: Cardiovascular Consultants, PA
state: Maryland
city: Worcester
country: United States
facility: University of Massachusettes
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Lincoln
country: United States
facility: Bryan LGH Heart Institute
state: Nebraska
city: Omaha
country: United States
facility: Alegent Health Immanuel Medical Center
state: Nebraska
city: Millburn
country: United States
state: New Jersey
city: Sewell
country: United States
facility: South Jersey Heart Group
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Buffalo
country: United States
facility: Buffalo General Hospital
state: New York
city: Fayetteville
country: United States
facility: Heart Care Center East
state: New York
city: Kingston
country: United States
facility: Hudson Valley Clinical Research
state: New York
city: New York
country: United States
facility: Saint Vincent Catholic Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cincinnati
country: United States
facility: Sterling Research Group
state: Ohio
city: Lorain
country: United States
facility: North Ohio Research, Ltd.
state: Ohio
city: Stow
country: United States
facility: City Cardiology Associates, Inc.
state: Ohio
city: Flourtown
country: United States
facility: Chestnut Hill Cardiology, Ltd.
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Carolina Research Associates
state: South Carolina
city: Memphis
country: United States
facility: The Stern Cardiovascular Center
state: Tennessee
city: Dallas
country: United States
facility: Cardiovascular Research Institute of Dallas Medical Center - Cardiologist Research Foundation
state: Texas
city: Houston
country: United States
facility: Med-Tech Research
state: Texas
city: Nassau Bay
country: United States
state: Texas
city: Tyler
country: United States
facility: Tyler Cardiovascular Consultants
state: Texas
city: Chesapeake
country: United States
facility: Cardiovascular Associates, Ltd.
state: Virginia
city: Elkhorn
country: United States
facility: Wisconsin Center for Clinical Research, LLC
state: Wisconsin
Study officials:
affiliation: Takeda
name: VP Clinical Science Strategy
role: STUDY_DIRECTOR
References: