Ruboxistaurin in New York Heart Failure Classification III-IV Patients

NCT02769611 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 2013-7007
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (3)

• Percent of patients experiencing at least one adverse event

  30 days

• Change in cardiac contractility as assessed by echocardiography.

  4 hours

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

  8 hours, 24 hours

Study Arms (3)

Ruboxistaurin 64 mg

EXPERIMENTAL

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

Drug: Ruboxistaurin

Ruboxistaurin 128 mg

EXPERIMENTAL

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

Drug: Ruboxistaurin

Ruboxistaurin 256 mg

EXPERIMENTAL

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

Drug: Ruboxistaurin

Interventions

Ruboxistaurin DRUG

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

Also known as: LY333531

Ruboxistaurin 128 mg; Ruboxistaurin 256 mg; Ruboxistaurin 64 mg

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Tennessee: lead
• The Christ Hospital: collaborator

Study Sites (1)

The Lindner Center for Research and Education at The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

ruboxistaurin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• John L Jefferies, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 11, 2016
• Study Start: June 28, 2017
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: June 6, 2022

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)