A Double-blind, Placebo-controlled Study of OPC-41061 in the Treatment of Cardiac Edema (Congestive Heart Failure)

Study Overview
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Brief Summary
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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.

Official Title
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A Double-blind, Placebo-controlled Study of OPC-41061 in the Treatment of Cardiac Edema (Congestive Heart Failure)

Conditions
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Edema, Cardiac

Intervention / Treatment
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* Drug: OPC-41061(Tolvaptan)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) 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. Male or female subjects age 20 or older and younger than 85 (at time of informed consent) 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) Subjects capable of giving informed consent to participate in the study of their own free will Exclusion Criteria: Subjects with acute heart failure Subjects with an assisted circulation device 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 Subjects who develop acute myocardial infarction within 30 days prior to the screening examination Subjects with a definite diagnosis of active myocarditis or amyloid cardiomyopathy 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 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. Subjects who are obese [body mass index (BMI, body weight (kg)/height (m)2 exceeding 35] Patients with supine systolic blood pressure exceeding 90 mmHg 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 Patients who are unable to take oral medication Female subjects who are pregnant, possibly pregnant, or lactating, or who plan to become pregnant Subjects who received any investigational drug other than OPC-41061 within 30 days prior to the screening examination Subjects who previously participated in this or any other study of OPC-41061 and received OPC-41061 Subjects otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>0mg | Drug: OPC-41061(Tolvaptan)<br>* 0, 15mg of OPC-41061 per day for 7days p.o. administration<br>|
| Experimental: 2<br>15mg OPC-41061 | Drug: OPC-41061(Tolvaptan)<br>* 0, 15mg of OPC-41061 per day for 7days p.o. administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Weight (Amount of Change) | Change in body weight from baseline at the time of final trial drug administration | baseline, Day 7 or at the time of final trial drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Weight (Percent Change) | Percent change in body weight from baseline at the time of final trial drug administration | baseline, Day 7 or at the time of final trial drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac edema, OPC-41061, Vasopressin antagonist