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

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.

Study Overview

• Status: Completed
• Conditions: Edema, Cardiac
• Intervention / Treatment: Drug: OPC-41061(Tolvaptan)

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chubu region, Japan
  • Chugoku region, Japan
  • Hokkaido region, Japan
  • Kanto region, Japan
  • Kinki region, Japan
  • Kyushu region, Japan
  • Shikoku region, Japan
  • Tohoku region, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 1; 0mg	Drug: OPC-41061(Tolvaptan); 0, 15mg of OPC-41061 per day for 7days p.o. administration
EXPERIMENTAL: 2; 15mg OPC-41061	Drug: OPC-41061(Tolvaptan); 0, 15mg of OPC-41061 per day for 7days p.o. administration

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (ACTUAL): October 1, 2008
• Study Completion (ACTUAL): October 1, 2008

Study Registration Dates

• First Submitted: April 17, 2007
• First Submitted That Met QC Criteria: April 17, 2007
• First Posted (ESTIMATE): April 19, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): February 4, 2014
• Last Update Submitted That Met QC Criteria: December 24, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: OPC-41061; Vasopressin antagonist; Cardiac edema
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Edema; Edema, Cardiac; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: 156-06-002