Ruboxistaurin in New York Heart Failure Classification III-IV Patients

Heart Failure Clinical Trial

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02769611
• Other study ID #: 2013-7007
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: June 28, 2017
• Est. completion date: January 1, 2022

Study information

• Verified date: May 2019
• Source: University of Tennessee
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 1, 2022
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

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.

Locations

Country	Name	City	State
United States	The Lindner Center for Research and Education at The Christ Hospital	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University of Tennessee	The Christ Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	48 hours
Primary	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	24 hours
Primary	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	12 hours
Primary	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	12 hours
Primary	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	12 hours
Secondary	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	30 days
Secondary	Change in cardiac contractility as assessed by echocardiography.	Transthoracic echocardiogram performed at baseline and 4 hours. Intent to treat population. Efficacy	4 hours
Secondary	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	8 hours, 24 hours