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Ruboxistaurin in New York Heart Failure Classification III-IV Patients

Primary Purpose

Heart Failure

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ruboxistaurin

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female, 30-75 years of age, inclusive
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
Patient must have had adequate therapy for acute decompensated HF (heart failure) episode prior to enrollment

Exclusion Criteria:

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

Sites / Locations

The Lindner Center for Research and Education at The Christ Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Ruboxistaurin 64 mg

Ruboxistaurin 128 mg

Ruboxistaurin 256 mg

Arm Description

ruboxistaurin, 64 mg as 1 capsule by mouth with water, 1 time administration

ruboxistaurin, 128 mg as 2 capsules by mouth with water, 1 time administration

ruboxistaurin, 256 mg as 4 capsules by mouth with water, 1 time administration

Outcomes

Primary Outcome Measures

Percent of patients with a new onset, clinically significant arrhythmia or conduction system disease,

EKG and continuous holter monitoring will be performed. Determination of clinically significant arrhythmia will be determined by a blinded electrophysiologist; intent to treat population

Percent of patients with significant prolongation in the corrected QT (QTc) interval

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

Percent of patients with significant increase in liver function tests

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

Percent of patients with a significant increase in serum creatinine not explained by diuretic use.

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

Percent of patient with a significant increase in serum creatine phosphokinase (CPK) levels

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

Percent of patients experiencing at least one adverse event

Adverse events will be assessed up to 30 days post study drug administration. Intent to treat population

Change in cardiac contractility as assessed by echocardiography.

Transthoracic echocardiogram performed at baseline and 4 hours. Intent to treat population. Efficacy

Change in self-reported well-being, fatigue and dyspnea

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

Full Information

NCT ID

NCT02769611

First Posted

May 10, 2016

Last Updated

June 1, 2022

Sponsor

University of Tennessee

Collaborators

The Christ Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02769611

Brief Title

Ruboxistaurin in New York Heart Failure Classification III-IV Patients

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.

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Withdrawn

Why Stopped

No funding

Study Start Date

June 28, 2017 (Actual)

Primary Completion Date

January 1, 2022 (Actual)

Study Completion Date

January 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Tennessee

Collaborators

The Christ Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ruboxistaurin 64 mg

Arm Type

Experimental

Arm Description

ruboxistaurin, 64 mg as 1 capsule by mouth with water, 1 time administration

Arm Title

Ruboxistaurin 128 mg

Arm Type

Experimental

Arm Description

ruboxistaurin, 128 mg as 2 capsules by mouth with water, 1 time administration

Arm Title

Ruboxistaurin 256 mg

Arm Type

Experimental

Arm Description

ruboxistaurin, 256 mg as 4 capsules by mouth with water, 1 time administration

Intervention Type

Drug

Intervention Name(s)

Ruboxistaurin

Other Intervention Name(s)

LY333531

Intervention Description

Dose escalation trial. 1st ten patients to receive 64 mg, next 10 patients to receive 128 mg, next 10 patients to receive 256 mg.

Primary Outcome Measure Information:

Title

Percent of patients with a new onset, clinically significant arrhythmia or conduction system disease,

Description

EKG and continuous holter monitoring will be performed. Determination of clinically significant arrhythmia will be determined by a blinded electrophysiologist; intent to treat population

Time Frame

48 hours

Title

Percent of patients with significant prolongation in the corrected QT (QTc) interval

Description

Time Frame

24 hours

Title

Percent of patients with significant increase in liver function tests

Description

Time Frame

12 hours

Title

Percent of patients with a significant increase in serum creatinine not explained by diuretic use.

Description

Time Frame

12 hours

Title

Percent of patient with a significant increase in serum creatine phosphokinase (CPK) levels

Description

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

Time Frame

12 hours

Secondary Outcome Measure Information:

Title

Percent of patients experiencing at least one adverse event

Description

Adverse events will be assessed up to 30 days post study drug administration. Intent to treat population

Time Frame

30 days

Title

Change in cardiac contractility as assessed by echocardiography.

Description

Transthoracic echocardiogram performed at baseline and 4 hours. Intent to treat population. Efficacy

Time Frame

4 hours

Title

Change in self-reported well-being, fatigue and dyspnea

Description

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

Time Frame

8 hours, 24 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female, 30-75 years of age, inclusive 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 Patient must have had adequate therapy for acute decompensated HF (heart failure) episode prior to enrollment Exclusion Criteria: Patients with acute coronary syndrome Resynchronization therapy initiated less than 90 days prior to enrollment (LVAD) left ventricular assist device or heart transplantation expected within the next 3 months Patients on hemodialysis or end stage renal disease (ESRD) Patients with serum albumin less than 3 g/dL or evidence of liver cirrhosis Patients with uncontrolled arterial hypertension (systolic blood pressure > 180 or diastolic blood pressure >110) Patients with severe valvular heart disease Patients with acute myocarditis Patients with serum creatinine >3.0 mg/dl or BUN >70 mg/dL Patients with hemodynamic instability or significant active arrhythmias Patients currently on intravenous inotropic therapy or those that have received inotropic therapy within the last 24 hours prior to study enrollment Patients currently on CYP3A inhibitors, or patients that have taken CYP3A inhibitors within 3 months prior to enrollment Patients with ongoing ischemia Patients who have had a myocardial infarction within 30 days prior to study enrollment Patients who are pregnant, nursing, or planning to become pregnant during the study period

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John L Jefferies, MD

Organizational Affiliation

Children's Hospital Medical Center, Cincinnati

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Lindner Center for Research and Education at The Christ Hospital

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45219

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Ruboxistaurin in New York Heart Failure Classification III-IV Patients

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