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Ruboxistaurin in New York Heart Failure Classification III-IV Patients

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ClinicalTrials.gov Identifier: NCT02769611
Recruitment Status : Recruiting
First Posted : May 11, 2016
Last Update Posted : February 13, 2018
Sponsor:
Collaborator:
The Christ Hospital
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
This study evaluates the effect of ruboxistaurin for its safety, tolerability, and effectiveness in treating adult patients with heart failure. Patients will receive 1 dose of oral ruboxistaurin.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Ruboxistaurin Phase 1 Phase 2

Detailed Description:
Ruboxistaurin is a drug initially developed for treatment of diabetic peripheral retinopathy. The proposed indication for ruboxistaurin in this study is the treatment of adult patients with New York Heart Failure Association (NYHA) Class III-IV heart failure. Ruboxistaurin is a protein kinase c-alpha (PKC-alpha) inhibitor and thus will produce an inotropic effect in the heart which holds the potential to improve cardiac function.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Phase I/II Dose Escalation Pilot Analysis of Ruboxistaurin (LY333531) for Safety in New York Heart Failure Classification III-IV Patients, As Well As For Efficacy in Acutely Augmenting Cardiac Function.
Actual Study Start Date : June 28, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Ruboxistaurin 64 mg
ruboxistaurin, 64 mg as 1 capsule by mouth with water, 1 time administration
Drug: Ruboxistaurin
Dose escalation trial. 1st ten patients to receive 64 mg, next 10 patients to receive 128 mg, next 10 patients to receive 256 mg.
Other Name: LY333531
Experimental: Ruboxistaurin 128 mg
ruboxistaurin, 128 mg as 2 capsules by mouth with water, 1 time administration
Drug: Ruboxistaurin
Dose escalation trial. 1st ten patients to receive 64 mg, next 10 patients to receive 128 mg, next 10 patients to receive 256 mg.
Other Name: LY333531
Experimental: Ruboxistaurin 256 mg
ruboxistaurin, 256 mg as 4 capsules by mouth with water, 1 time administration
Drug: Ruboxistaurin
Dose escalation trial. 1st ten patients to receive 64 mg, next 10 patients to receive 128 mg, next 10 patients to receive 256 mg.
Other Name: LY333531



Primary Outcome Measures :
  1. Percent of patients with a new onset, clinically significant arrhythmia or conduction system disease, [ Time Frame: 48 hours ]
    EKG and continuous holter monitoring will be performed. Determination of clinically significant arrhythmia will be determined by a blinded electrophysiologist; intent to treat population

  2. Percent of patients with significant prolongation in the corrected QT (QTc) interval [ Time Frame: 24 hours ]
    Interpreted by a blinded electrophysiologist. A significant QTc prolongation will be defined as an increase from normal baseline (<440 msec) to greater than 440 msec OR an increase of equal to or more than 5% from baseline for those subjects with a baseline QTc of >440 msec.; Intent to treat population

  3. Percent of patients with significant increase in liver function tests [ Time Frame: 12 hours ]
    An abnormal change in liver function tests will be defined as an increase to 2x the upper limits of normal for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) OR a 50% increase from baseline values. Intent to treat population

  4. Percent of patients with a significant increase in serum creatinine not explained by diuretic use. [ Time Frame: 12 hours ]
    An abnormal change in serum creatinine will be defined as a 50% increase from baseline values. Of note, changes in Blood Urea Nitrogen (BUN) and creatinine may be secondary to diuretic use and intravascular volume depletion. Intent to treat population

  5. Percent of patient with a significant increase in serum creatine phosphokinase (CPK) levels [ Time Frame: 12 hours ]
    An abnormal change in serum CPK will be defined as an increase to 2x the upper limits or normal OR a 50% increase from baseline values. Intent to treat population


Secondary Outcome Measures :
  1. Percent of patients experiencing at least one adverse event [ Time Frame: 30 days ]
    Adverse events will be assessed up to 30 days post study drug administration. Intent to treat population

  2. Change in cardiac contractility as assessed by echocardiography. [ Time Frame: 4 hours ]
    Transthoracic echocardiogram performed at baseline and 4 hours. Intent to treat population. Efficacy

  3. Change in self-reported well-being, fatigue and dyspnea [ Time Frame: 8 hours, 24 hours ]
    All subjects will undergo assessment of self-reported global well-being, fatigue and dyspnea via a visual-analogue scale that ranges from 0-100. Intent to treat population



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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, 30-75 years of age, inclusive
  2. NYHA Class III-IV heart failure (HF) confirmed left ventricular systolic dysfunction with left ventricular ejection fraction (LVEF) <40% as assessed by noninvasive imaging studies such as echocardiography or cardiac MRI within the last 6 months admitted with decompensated heart failure and almost ready for clinical discharge
  3. Patient must have had adequate therapy for acute decompensated HF (heart failure) episode prior to enrollment

Exclusion Criteria:

  1. Patients with acute coronary syndrome
  2. Resynchronization therapy initiated less than 90 days prior to enrollment
  3. (LVAD) left ventricular assist device or heart transplantation expected within the next 3 months
  4. Patients on hemodialysis or end stage renal disease (ESRD)
  5. Patients with serum albumin less than 3 g/dL or evidence of liver cirrhosis
  6. Patients with uncontrolled arterial hypertension (systolic blood pressure > 180 or diastolic blood pressure >110)
  7. Patients with severe valvular heart disease
  8. Patients with acute myocarditis
  9. Patients with serum creatinine >3.0 mg/dl or BUN >70 mg/dL
  10. Patients with hemodynamic instability or significant active arrhythmias
  11. Patients currently on intravenous inotropic therapy or those that have received inotropic therapy within the last 24 hours prior to study enrollment
  12. Patients currently on CYP3A inhibitors, or patients that have taken CYP3A inhibitors within 3 months prior to enrollment
  13. Patients with ongoing ischemia
  14. Patients who have had a myocardial infarction within 30 days prior to study enrollment
  15. Patients who are pregnant, nursing, or planning to become pregnant during the study period

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02769611


Contacts
Contact: John Jefferies, MD (513)803-1675 j.jefferies@cchmc.org

Locations
United States, Ohio
The Lindner Center for Research and Education at The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Gregory Egnaczyk, MD    513-585-1777      
Principal Investigator: Gregory Egnaczyk, MD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
The Christ Hospital
Investigators
Principal Investigator: John L Jefferies, MD Children's Hospital Medical Center, Cincinnati

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02769611     History of Changes
Other Study ID Numbers: 2013-7007
First Posted: May 11, 2016    Key Record Dates
Last Update Posted: February 13, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Ruboxistaurin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action