Ruboxistaurin in New York Heart Failure Classification III-IV Patients

Phase 1

Withdrawn

• Conditions: Heart Failure
• Interventions: Drug: Ruboxistaurin

• Registration Number: NCT02769611
• Lead Sponsor: University of Tennessee

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.

Study Timeline

• Study First Submitted: 2016-05-10
• Study First Submitted QC: 2016-05-10
• Study First Posted: 2016-05-11
• Study Start: 2017-06-28
• Status Verified: 2019-05
• Primary Completion: 2022-01-01
• Study Completion: 2022-01-01
• Last Update Submitted: 2022-06-01
• Last Update Posted: 2022-06-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ruboxistaurin 64 mg	Ruboxistaurin	ruboxistaurin, 64 mg as 1 capsule by mouth with water, 1 time administration
Ruboxistaurin 128 mg	Ruboxistaurin	ruboxistaurin, 128 mg as 2 capsules by mouth with water, 1 time administration
Ruboxistaurin 256 mg	Ruboxistaurin	ruboxistaurin, 256 mg as 4 capsules by mouth with water, 1 time administration

Primary Outcome Measures

Name	Time	Method
Percent of patients with a new onset, clinically significant arrhythmia or conduction system disease,	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
Percent of patients with significant prolongation in the corrected QT (QTc) interval	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
Percent of patients with significant increase in liver function tests	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
Percent of patients with a significant increase in serum creatinine not explained by diuretic use.	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
Percent of patient with a significant increase in serum creatine phosphokinase (CPK) levels	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

Name	Time	Method
Change in self-reported well-being, fatigue and dyspnea	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
Percent of patients experiencing at least one adverse event	30 days	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.	4 hours	Transthoracic echocardiogram performed at baseline and 4 hours. Intent to treat population. Efficacy

Trial Locations

Locations (1)

The Lindner Center for Research and Education at The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States