A Dose-finding Study of OPC-41061 in Treatment of Cardiac Edema (Congestive Heart Failure)

Inclusion criteria

• Patients with CHF who exhibit edema, jugular venous distention, hepatomegaly, pulmonary congestion, or 3rd sound due to extracellular volume expansion
• Hospitalized patients or patients who can be hospitalized for the study from the commencement of the observation period to the end-of-study examination
• Men and women between the ages of 20 and 80 (non-inclusive) at the time of giving consent
• Patients who have taken furosemide at 40 mg/d or more (oral dosing) without alteration of dosage for the 3 days of the observation period
• Patients whose body weight has been stable (±1.0 kg) for 2 days prior to commencement of study drug administration

Exclusion criteria

• Patients with unstable heart failure (acute heart failure, acute exacerbation of chronic heart failure, etc)
• Patients with an implanted ventricular assist device
• Patients who have undergone or are scheduled to undergo any of the following procedures

• Heart surgery involving thoracotomy within 60 days prior to the screening examination
• Pacemaker implant surgery involving bilateral pacing within 60 days prior to the screening examination
• Angioplasty, electrophysiologic device implantation, ventricular assist device implantation, heart transplant, or other cardiac surgery scheduled within 30 days after the screening examination
• Patients with any of the following diseases, complications, or symptoms

• Suspected hypovolemia
• Onset of acute myocardial infarction within 30 days prior to the screening examination
• Hypertrophic cardiomyopathy (excluding diastolic phase)
• Definitively diagnosed active myocarditis or amyloid cardiomyopathy
• Valvular heart disease with significant stenosis
• Untreated thyroid disease
• Progressive neurological disease (Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc) or severe episodic neurological disease (epilepsy, Guillain-Barre syndrome, etc)
• Diabetes with poor glycemic control
• Anuria
• Hepatic coma
• Hyponatremia of moderate or greater severity (serum Na < 120 mEq/L)
• Patients with a history of the following conditions

• Occurrence of sustained ventricular tachycardia or ventricular fibrillation within 30 days prior to the screening examination (except for patients using an implantable cardioverter-defibrillator)
• Evident cerebral infarction
• Multiple stroke
• Occurrence of a cerebrovascular accident within 30 days prior to the screening examination
• Hypersensitivity or idiosyncratic reaction to benzazepine derivatives, such as benazapril
• Patients with a history of drug abuse or alcoholism in the past year
• Patients in a state of morbid obesity with a body mass index (weight[kg] ÷ height [m]2) over 35
• Patients with a supine systolic arterial blood pressure of less than 90 mmHg
• Patients with any of the following abnormal laboratory values: Hemoglobin <9 g/dL, total bilirubin >3.0 mg/dL, serum creatine >3.0 mg/dL, serum Na >147 mEq/L, or serum K >5.5 mEq/L
• Patients not capable of taking oral medication
• Patients who are nursing, pregnant, capable of pregnancy, or intending to become pregnant during or shortly after the study period
• Patients who have taken a study drug other than OPC-41061 within 30 days prior to screening
• Patients who have previously taken OPC-41061 in this study or another study of OPC-41061
• Patients otherwise judged by the principal investigator or attending investigator to be inappropriate for inclusion in the study (eg, patients with hepatic cirrhosis, renal disease, etc.)