A Clinical Pharmacological Study of OPC-41061 in the Treatment of Cardiac Edema (Congestive Heart Failure)
Condition: Cardiac Edema
MeSH terms: Heart Failure; Edema, Cardiac; Edema
Intervention: OPC-41061(Tolvaptan); Placebo
Intervention description: Subjects will be orally administered OPC-41061 7.5 mg or 15 mg once daily after breakfast for seven days.; Subjects will be orally administered placebo once daily after breakfast for seven days.
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: 20.0
Sex: All
Minimum age: 20 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Vasopressin antagonist; Cardiac Edema; Diuretics

Summary:

      To investigate the pharmacokinetics, pharmacodynamics (urine volume and fluid intake),
      efficacy(body weight, pulmonary congestion and other congestions including cardiothoracic
      ratio) and safety of 7-day repeated oral administration of OPC-41061 at 7.5 mg or 15 mg in
      congestive heart failure (cardiac edema) patients with extracellular volume expansion despite
      the use of a diuretic.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects with cardiac edema receiving diuretic treatments 7 days prior to the start of
             treatment.

          2. Subjects able to receive a daily regular dosage of furosemide at 40-mg to 80-mg from
             the observation period until the end-of-treatment examination.

          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 age of 20 and 85, inclusive.

          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-dosing examination 2.

          6. Subjects capable of giving informed consent to participate in the study of their own
             free will.

        Exclusion Criteria:

          1. Subjects with heart failure with markedly fluctuating symptoms.

          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 well-defined 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.

          8. Subjects who are morbidly obese (body mass index exceeding 35).

          9. Subjects with systolic blood pressure in the decubitus position below 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. Subjects 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.