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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00050076
First received: November 20, 2002
Last updated: January 31, 2012
Last verified: January 2012
  Purpose

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 Intervention Phase
Congestive Heart Failure
Drug: MCC-135
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change from baseline in the serum levels of brain natriuretic peptide [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in the Minnesota living with heart failure questionnaire score [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • Regular rate (heart rate) variability as measured by 24-hour Holter monitoring [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • Disease progression status measured by New York Heart Association class [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • Disease progression status measured by Global Clinical Status [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]
  • Disease progression status measured by Clinical Composite [ Time Frame: At Final Visit. ] [ Designated as safety issue: No ]

Enrollment: 204
Study Start Date: August 2002
Study Completion Date: August 2003
Primary Completion Date: August 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00050076

  Show 53 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: VP Clinical Science Strategy Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00050076     History of Changes
Other Study ID Numbers: 01-02-TL-MCC135-001, U1111-1127-6077
Study First Received: November 20, 2002
Last Updated: January 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Congestive Heart Failure
Cardiac Failure
Heart Decompensation
Drug Therapy

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 19, 2014