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A Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Bendavia™ (MTP-131) in Patients With Heart Failure

Phase 1
Withdrawn
Conditions
Heart Failure
Interventions
Drug: Placebo
Registration Number
NCT02388529
Lead Sponsor
Stealth BioTherapeutics Inc.
Brief Summary

This study is a single-center, randomized, double-blind, placebo-controlled study in patients with stable heart failure to evaluate the safety, tolerability, pharmacokinetics, and efficacy of multiple ascending doses of Bendavia™ (MTP-131) intravenous infusion.

Detailed Description

Not available

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • LVEF ≤45% by 2-D echocardiogram.
  • Diagnosis of New York Heart Association Class II or III HF for a minimum of 6 months prior to the Screening Visit.
  • HF is considered to be stable, in the judgment of the Principal Investigator and no hospitalization related to HF has occurred within the 1 month prior to the Screening Visit.
  • Treatment with appropriate pharmacologic therapy for HF including, but not limited to, angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB), and an evidence-based beta blocker for the treatment of HF
  • Females of child-bearing potential must have a negative serum pregnancy test at the Screening Visit.
  • Written informed consent obtained that strictly adheres to the written guidelines from the local Ethical Committee (EC).
Exclusion Criteria
  • Unstable angina pectoris within 1 month before initiation of screening procedures. Unstable angina is defined as the occurrence of chest pain more frequently than usual, pain at rest or upon minimal exertion, or protracted episodes of pain without any discernible trigger, and/or chest pain that persists despite use of vasodilatory therapy (e.g., nitroglycerin).

  • Coronary or peripheral artery revascularization procedure within 2 months prior to the Screening Visit.

  • An acute myocardial infarction within 3 months prior to the Screening Visit.

  • Supine resting heart rate ≥ 100 beats per minute after 5 minutes rest.

  • Uncontrolled hypertension defined as a systolic blood pressure (BP) >180 mm Hg or a diastolic BP >110 mm Hg on at least 2 consecutive readings.

  • Requirement for valve or other cardiac surgery (e.g., pericardectomy).

  • Cardiac surgery or valvuloplasty within 2 month prior to the Screening Visit.

  • General surgery within 1 month prior to the Screening Visit.

  • Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic left ventricular aneurysm.

  • Cerebrovascular accident or transient ischemic attack within 3 months prior to the Screening Visit.

  • Liver enzyme (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) elevation >3x the upper limit of normal (ULN).

  • Estimated glomerular filtration rate (eGFR) <30 mL/min, using the Modification of Diet in Renal Disease (MDRD) Study equation.

  • Known active drug or alcohol abuse.

  • Active infection requiring systemic treatment or surgical intervention.

  • Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study.

  • Female patients who are pregnant or breastfeeding.

    • Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Low doseMTP-131-
Intermediate doseMTP-131-
High doseMTP-131-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Incidence of Adverse EventsAssessed up to Day 33
Mean peak plasma concentration (Cmax) of MTP-131 (ng/ml) in each cohortAssessed up to Day 12
Secondary Outcome Measures
NameTimeMethod
Changes in echocardiographic LV end-systolic volume (LVESV)Assessed up to Day 33
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