Ruboxistaurin in New York Heart Failure Classification III-IV Patients

June 1, 2022 updated by: University of Tennessee

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.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • The Lindner Center for Research and Education at The Christ Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • 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 Names:
  • LY333531

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
48 hours
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
24 hours
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
12 hours
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
12 hours
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
12 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
30 days
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
4 hours
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
8 hours, 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Tennessee

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Christ Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: John L Jefferies, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 28, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 10, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 11, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 6, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2013-7007

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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