Ruboxistaurin in New York Heart Failure Classification III-IV Patients

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.

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