A Dose-finding Study of OPC-41061 in Treatment of Cardiac Edema (Congestive Heart Failure)
Condition: Heart Failure, Congestive; Edema
MeSH terms: Heart Failure; Edema
Intervention: OPC-41061(Tolvaptan)
Intervention MeSH terms: Tolvaptan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 122.0
Sex: All
Minimum age: 20 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: OPC-41061; Tolvaptan; Heart Failure; Edema; Extracellular volume expansion

Summary:

      This drug is being developed to treat cardiac edema. The primary purpose of this study is to
      investigate the dose response for body weight in seven-day repeated oral administration of
      OPC-41061 at 15, 30, and 45 mg or placebo in patients with extracellular volume expansion
      secondary to CHF despite taking furosemide at 40 mg/d or more. This study is being conducted
      in Japan.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with CHF who exhibit edema, jugular venous distention, hepatomegaly,
             pulmonary congestion, or 3rd sound due to extracellular volume expansion

          2. Hospitalized patients or patients who can be hospitalized for the study from the
             commencement of the observation period to the end-of-study examination

          3. Men and women between the ages of 20 and 80 (non-inclusive) at the time of giving
             consent

          4. 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

          5. Patients whose body weight has been stable (±1.0 kg) for 2 days prior to commencement
             of study drug administration

        Exclusion Criteria:

          1. Patients with unstable heart failure (acute heart failure, acute exacerbation of
             chronic heart failure, etc)

          2. Patients with an implanted ventricular assist device

          3. 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

          4. 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)

          5. 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

          6. Patients with a history of drug abuse or alcoholism in the past year

          7. Patients in a state of morbid obesity with a body mass index (weight[kg] ÷ height
             [m]2) over 35

          8. Patients with a supine systolic arterial blood pressure of less than 90 mmHg

          9. 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

         10. Patients not capable of taking oral medication

         11. Patients who are nursing, pregnant, capable of pregnancy, or intending to become
             pregnant during or shortly after the study period

         12. Patients who have taken a study drug other than OPC-41061 within 30 days prior to
             screening

         13. Patients who have previously taken OPC-41061 in this study or another study of
             OPC-41061

         14. 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.)