Ruboxistaurin in New York Heart Failure Classification III-IV Patients

• Sponsor: University of Tennessee (Other)
• Overall Status: Withdrawn
• CT.gov ID: NCT02769611
• Collaborator: The Christ Hospital (Other)
• Enrollment: 0
• Location: 1
• Arms: 3
• Actual Duration (Months): 54.1
• Patients Per Site Per Month: 0

Study Details

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.

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 Design

• Study Type: Interventional
• Actual Enrollment: 0 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: Jun 28, 2017
• Actual Primary Completion Date: Jan 1, 2022
• Actual Study Completion Date: Jan 1, 2022

Arms and Interventions

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 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

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

3. 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

4. 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

5. 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

1. 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

2. Change in cardiac contractility as assessed by echocardiography. [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 [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Lindner Center for Research and Education at The Christ Hospital	Cincinnati	Ohio	United States	45219

Sponsors and Collaborators

• University of Tennessee
• The Christ Hospital

Investigators

• Principal Investigator: John L Jefferies, MD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Tennessee
• ClinicalTrials.gov Identifier: NCT02769611
• Other Study ID Numbers: 2013-7007
• First Posted: May 11, 2016
• Last Update Posted: Jun 6, 2022
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• 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; Ruboxistaurin

Study Results

No Results Posted as of Jun 6, 2022