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

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

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.

Study Overview

• Status: Completed
• Conditions: Congestive Heart Failure
• Intervention / Treatment: Drug: MCC-135; Drug: MCC-135; Drug: MCC-135; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Maricopa Medical Center
    • Tucson, Arizona, United States, 85724
      • University of Arizona Medical Center
  • California
    • Carmichael, California, United States, 95608
      • Capitol Intervention Cardiology
    • Encinitas, California, United States, 92024
      • San Diego Cardiovascular
    • Los Angeles, California, United States, 90033
      • LAC & USC Medical Center
    • Redondo Beach, California, United States, 90027
      • ARI Clinical Trials, Inc Arrhythmia Research & Cardiology Health Center
    • Roseville, California, United States, 95661
      • Clinical Trials Research
    • Sacramento, California, United States, 95825
      • Sacramento Heart & Vascular Medical Associates
    • San Diego, California, United States, 92103
      • University of California San Diego
    • Santa Ana, California, United States, 92705
      • Apex Research Institute
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Cardiology Consultants PA
    • Fort Lauderdale, Florida, United States, 33308
      • Cardiology Associates of Fort Lauderdale
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Sarasota, Florida, United States, 34239
      • Cardiovascular Center of Sarasota
  • Georgia
    • Augusta, Georgia, United States, 30904
      • Southern Clinical Research & Management
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Medical Group of Fort Wayne, PC
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Louisville Cardiology Medical Group, PSC
    • Louisville, Kentucky, United States, 40202
      • Medical Center Cardiologist
  • Louisiana
    • Chalmette, Louisiana, United States, 70043
      • LOUISIANA HEART Center
    • New Orleans, Louisiana, United States, 70119
      • New Orleans Center for Clinical Research
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic
    • Shreveport, Louisiana, United States, 71103
      • Cardiac Center of Louisiana, LLC
  • Maryland
    • Annapolis, Maryland, United States, 21114
      • Cardiology Associates, Pc
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Hospital
    • Takoma Park, Maryland, United States, 20901
      • Cardiovascular Consultants, PA
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusettes
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Bryan LGH Heart Institute
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
  • New Jersey
    • Millburn, New Jersey, United States, 07041
    • Sewell, New Jersey, United States, 08080
      • South Jersey Heart Group
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College Of Medicine
    • Buffalo, New York, United States, 14203
      • Buffalo General Hospital
    • Fayetteville, New York, United States, 13066
      • Heart Care Center East
    • Kingston, New York, United States, 12401
      • Hudson Valley Clinical Research
    • New York, New York, United States, 10011
      • Saint Vincent Catholic Medical Center
    • Rochester, New York, United States, 14618
      • University of Rochester
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group
    • Lorain, Ohio, United States, 44053
      • North Ohio Research, Ltd.
    • Stow, Ohio, United States, 44224
      • City Cardiology Associates, Inc.
  • Pennsylvania
    • Flourtown, Pennsylvania, United States, 19031
      • Chestnut Hill Cardiology, Ltd.
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Columbia, South Carolina, United States, 29206
      • Carolina Research Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • The Stern Cardiovascular Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Cardiovascular Research Institute of Dallas Medical Center - Cardiologist Research Foundation
    • Houston, Texas, United States, 77055
      • Med-Tech Research
    • Nassau Bay, Texas, United States, 77058
    • Tyler, Texas, United States, 75701
      • Tyler Cardiovascular Consultants
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Cardiovascular Associates, Ltd.
  • Wisconsin
    • Elkhorn, Wisconsin, United States, 53121
      • Wisconsin Center for Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the serum levels of brain natriuretic peptide	At Final Visit.

Secondary Outcome Measures

Outcome Measure	Time Frame
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.

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start: August 1, 2002
• Primary Completion (ACTUAL): August 1, 2003
• Study Completion (ACTUAL): August 1, 2003

Study Registration Dates

• First Submitted: November 20, 2002
• First Submitted That Met QC Criteria: November 20, 2002
• First Posted (ESTIMATE): November 21, 2002

Study Record Updates

• Last Update Posted (ESTIMATE): February 2, 2012
• Last Update Submitted That Met QC Criteria: January 31, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Drug Therapy; Congestive Heart Failure; Cardiac Failure; Heart Decompensation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 01-02-TL-MCC135-001; U1111-1127-6077 (REGISTRY: WHO)