A Dose-Defining Study of CXL-1020 in Patients With Systolic Heart Failure

Exclusion Criteria

• •In order to be eligible for randomization, a patient MUST NOT:
• •Have participated in any investigational drug study, SERCa gene therapy or cellular myocardial transplant study within 30 days preceding randomization or have previously received therapy with CXL-1020
• •Have received a parenteral or oral dose of diuretics or other hemodynamically active therapy within 3 hours of the baseline hemodynamic assessment
• •Have received intravenous inotropes, inodilators or vasodilators (amrinone, digoxin, dopamine, dobutamine, enoximone, levosimendan, milrinone, nesiritide, nitroglycerine or nitroprusside) for more than 4 hours and within 12 hours prior to randomization to treatment with study drug
• •Have a heart rate \<50 or ≥ 90 BPM at baseline prior to randomization
• •Have a blood pressure \>150 Systolic and/or \>95 diastolic mmHg at baseline prior to randomization
• •Have a systolic blood pressure of less than 100 mmHg at baseline prior to randomization
• •Be in atrial fibrillation/flutter at the time of randomization or have a history of recent intermittent A-fib/flutter within the previous week
• •Have non-sustained VT (HR \> 120 bpm) of 10 beats or more during bedside monitoring prior to randomization or excessive VPB's or complex multifocal ventricular ectopy exceeding 10 beats per minute on a 2 minute rhythm strip taken within 10 minutes prior to randomization
• •Have a history of successful cardiac resuscitation within the past 2 years. (Inappropriate ICD firings for non lethal arrhythmias are not exclusionary)
• •Be hospitalized with acute coronary syndrome or acute myocardial infarction during the previous 90 days prior to randomization
• •Have a history of stroke (CVA) or transient ischemic attack (TIA) within six months prior to randomization
• •Have a concurrent history of CCS Class III or IV angina
• •Be a patient whose HF etiology is attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic cardiomyopathy (as defined by any wall thickness \> 1.8 cm) or uncorrected severe valvular disease
• •Be receiving concomitant oral or parenteral therapy with any antiarrhythmic drugs other than amiodarone or dronedarone. (only oral therapy is allowed for these agents)
• •Have unsuitable echocardiographic windows for the Echo assessments (applies only to Strata B)
• •Have a screening or baseline serum Na \< 130 mEq/l or \> 145 mEq/l; a serum K \< 3.5 mEq/l or \> 5.5 mEq/l; a serum Ca \< 7.5 mg/dl or \> 10.2 mg/dl; or a serum Mg \< 1.6 mEq/l or \> 3.0 mEq/l., or a digoxin level above 1ng/ml
• •Have a baseline serum creatinine \> 2.5 mg/dl; an ALT or AST \>3 times the upper normal limit; or a hemoglobin \< 10 g/dl
• •Have taken ethanol within 24 hours (with a positive ethanol breath test or blood test) or a PDE5 inhibitor within 96 hours of study drug administration
• •Have other clinically significant laboratory or medical conditions that, in the opinion of the Investigator, make the patient unsuitable for evaluation in the study
• •Be receiving a drug which is expected to possess the potential for a clinically significant pharmacokinetic interaction with CXL-1020, as defined in the investigational drug brochure (IDB).
• •Be the recipient of a myocardial restraint device or flap
• •Have an anticipated survival of less than 90 days for any reason Note: Patients receiving cardiac resynchronization therapy for HF are eligible and pacemaker settings have not been changed on this hospitalization and can be left unchanged for the study.