A Study of OPC-41061 in Subjects With Cardiac-induced Edema (Congestive Heart Failure)

Inclusion criteria

• Subjects with cardiac edema receiving diuretic treatment since 7 days prior to the commencement of study drug administration.
• Subjects receiving one of the following diuretic treatments since 3 days prior to the commencement of study drug administration without changing the dose or dosing regimen (including subjects scheduled to start treatment during the run-in observation period).

• 1. A loop diuretic at a daily dosage equivalent to 40 mg or more of furosemide
• 2. Concomitant administration of a loop diuretic and a thiazide diuretic (at any doses)
• 3. Concomitant administration of a loop diuretic and an anti-aldosterone drug (at any doses)
• CHF patients with lower limb edema, jugular venous distention, or pulmonary congestion due to extracellular volume expansion.
• Male or female subjects between the ages of 20 and 85, inclusive (at time of informed consent)
• Subjects able to stay at the study site from the day before the start of the run-in observation period until completion of post-treatment observation 2 (7 to 10 days after final study drug administration)
• Subjects capable of giving informed consent to participate in the study of their own free will

Exclusion criteria

• Heart failure patients with markedly fluctuating symptoms
• Patients with an assisted circulation device
• Patients with any of the following complications or symptoms:

• 1. Suspected decrease in circulatory blood flow ，
• 2. Hypertrophic cardiomyopathy (other than dilated phase)，
• 3. Cardiac valve disease with significant heart valve stenosis，
• 4. Hepatic coma
• Patients who develop acute myocardial infarction within 30 days prior to the screening examination
• Patients with a definite diagnosis of active myocarditis or amyloid cardiomyopathy
• Subjects with any of the following complications or symptoms:

• 1. Poorly controlled diabetes melllitus，
• 2. Anuria，
• 3. Urination impaired due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause
• Subjects with any of the following disease histories:

• 1. Sustained ventricular tachycardia or ventricular fibrillation within 30 days prior to the screening examination in subjects without an implanted defibrillator，
• 2. Cerebrovascular disorder within 6 months prior to the screening examination (other than asymptomatic cerebral infarction)，
• 3. A history of hypersensitivity or idiosyncratic reaction to benzazepine derivatives such as mozavaptan hydrochloride or benazepril hydrochloride.
• Subjects who are severely obese [body mass index (BMI, body weight (kg)/height (m)2] exceeding 35]
• Subjects with systolic blood pressure in the decubitus position exceeding 90 mmHg
• Subjects with any of the following abnormal laboratory values:

• 1. Total bilirubin > 3.0 mg/dL,
• 2. serum creatinine > 3.0 mg/dL,
• 3. serum sodium > 147 mEq/L,
• 4. serum potassium > 5.5 mEq/L
• Patients who are unable to take oral medication
• Female subjects who are pregnant, possibly pregnant, or lactating, or who plan to become pregnant during the study period
• Subjects who received any investigational drug other than OPC-41061 within 30 days prior to the screening examination
• Subjects otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the study