A Clinical Pharmacological Study of OPC-41061 in the Treatment of Cardiac Edema (Congestive Heart Failure)

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Kanto region, Japan
  • Kyushu 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 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.

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: 2; placebo	Drug: Placebo; Subjects will be orally administered placebo once daily after breakfast for seven days.
EXPERIMENTAL: 1; OPC-41061	Drug: OPC-41061(Tolvaptan); Subjects will be orally administered OPC-41061 7.5 mg or 15 mg once daily after breakfast for seven days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight	The body weight change from baseline at the time of final trial drug administration	Baseline, at the time of final trial drug administration

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (ACTUAL): January 1, 2009
• Study Completion (ACTUAL): January 1, 2009

Study Registration Dates

• First Submitted: September 3, 2007
• First Submitted That Met QC Criteria: September 3, 2007
• First Posted (ESTIMATE): September 5, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): December 25, 2013
• Last Update Submitted That Met QC Criteria: November 6, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Diuretics; 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: 156-06-004