A Study of OPC-41061 in Subjects With Cardiac-induced Edema (Congestive Heart Failure)
Condition: Cardiac Edema
MeSH terms: Heart Failure; Edema, Cardiac; Edema
Intervention: OPC-41061 （Tolvaptan)
Intervention description: 15-30mg/day,daily for 14days
Intervention MeSH terms: Tolvaptan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 20 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Vasopressin antagonist , Cardiac Edema ,Diuretics

Summary:

      To investigate the plasma drug level, efficacy, and safety of 7-day repeated oral
      administration of OPC-41061 at 15 mg/day (treatment period 1) and subsequent 7-day repeated
      administration of OPC-41061 at 15 mg/day or 30 mg/day if diuretic effect is insufficient
      (treatment period 2) in congestive heart failure (CHF) patients with extracellular volume
      expansion despite conventional diuretic therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects with cardiac edema receiving diuretic treatment since 7 days prior to the
             commencement of study drug administration.

          2. 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)

          3. CHF patients with lower limb edema, jugular venous distention, or pulmonary congestion
             due to extracellular volume expansion.

          4. Male or female subjects between the ages of 20 and 85, inclusive (at time of informed
             consent)

          5. 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)

          6. Subjects capable of giving informed consent to participate in the study of their own
             free will

        Exclusion Criteria:

          1. Heart failure patients with markedly fluctuating symptoms

          2. Patients with an assisted circulation device

          3. 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

          4. Patients who develop acute myocardial infarction within 30 days prior to the screening
             examination

          5. Patients with a definite diagnosis of active myocarditis or amyloid cardiomyopathy

          6. 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

          7. 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.

          8. Subjects who are severely obese [body mass index (BMI, body weight (kg)/height (m)2]
             exceeding 35]

          9. Subjects with systolic blood pressure in the decubitus position exceeding 90 mmHg

         10. 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

         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 during the study period

         13. Subjects who received any investigational drug other than OPC-41061 within 30 days
             prior to the screening examination

         14. Subjects otherwise judged by the investigator or subinvestigator to be inappropriate
             for inclusion in the study