A Double-blind, Placebo-controlled Study of OPC-41061 in the Treatment of Cardiac Edema (Congestive Heart Failure)
Condition: Edema, Cardiac
MeSH terms: Heart Failure; Edema, Cardiac; Edema
Intervention: OPC-41061(Tolvaptan)
Intervention description: 0, 15mg of OPC-41061 per day for 7days p.o. administration
Intervention MeSH terms: Tolvaptan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 110.0
Sex: All
Minimum age: 20 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Cardiac edema; OPC-41061; Vasopressin antagonist

Summary:

      To evaluate the efficacy and safety of 7-day repeated oral administration of OPC-41061 15 mg
      or placebo in congestive heart failure (CHF) patients with extracellular volume expansion
      despite the use of a conventional diuretic.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects receiving one of the following diuretic treatments (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)

          2. CHF patients with lower limb edema, jugular venous distention, or pulmonary congestion
             due to extracellular volume expansion Patients with pulmonary congestion can be
             enrolled if pulmonary congestion is confirmed on chest x-ray taken within 14 days
             prior to the screening examination.

          3. Male or female subjects age 20 or older and younger than 85 (at time of informed
             consent)

          4. Subjects who are able to stay at the study site from the day before the start of the
             run-in observation period until completion of postdosing examination 2 (7 to 10 days
             after final study drug administration)

          5. Subjects capable of giving informed consent to participate in the study of their own
             free will

        Exclusion Criteria:

          1. Subjects with acute heart failure

          2. Subjects with an assisted circulation device

          3. Subjects 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

          4. Subjects who develop acute myocardial infarction within 30 days prior to the screening
             examination

          5. Subjects with a definite diagnosis of active myocarditis or amyloid cardiomyopathy

          6. Subjects with any of the following complications or symptoms: (1)Diabetes mellitus
             with poorly controlled blood glucose, (2)Anuria, (3)Urination impaired due to urinary
             tract stricture, urinary calculus, tumor in urinary tract, or other cause

          7. Subjects with a history of any of the following diseases: (1)Sustained ventricular
             tachycardia or ventricular fibrillation within 30 days prior to the screening
             examination in patients without an implanted defibrillator, (2)Cerebrovascular
             disorder within 6 months prior to the screening examination (other than asymptomatic
             cerebral infarction), (3)Hypersensitivity or idiosyncratic reaction to benzazepine
             derivatives such as mozavaptan hydrochloride or benazepril hydrochloride.

          8. Subjects who are obese [body mass index (BMI, body weight (kg)/height (m)2 exceeding
             35]

          9. Patients with supine systolic blood pressure exceeding 90 mmHg

         10. Subjects with any of following abnormal laboratory values: (1)Total bilirubin
             exceeding 3.0 mg/dL, (2)serum creatinine exceeding 3.0 mg/dL, (3)serum sodium
             exceeding 147 mEq/L, (4)serum potassium exceeding 5.5 mEq/L

         11. Patients who are unable to take oral medication

         12. Female subjects who are pregnant, possibly pregnant, or lactating, or who plan to
             become pregnant

         13. Subjects who received any investigational drug other than OPC-41061 within 30 days
             prior to the screening examination

         14. Subjects who previously participated in this or any other study of OPC-41061 and
             received OPC-41061

         15. Subjects otherwise judged by the investigator or subinvestigator to be inappropriate
             for inclusion in the study