A Dose-finding Study of OPC-41061 in Treatment of Cardiac Edema (Congestive Heart Failure)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Dose Response of OPC-41061 in Congestive Heart Failure Patients With Extracellular Volume Expansion

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.

Study Overview

• Status: Completed
• Conditions: Edema; Heart Failure, Congestive
• Intervention / Treatment: Drug: OPC-41061(Tolvaptan)

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Otsuka Pharmaceutical Co., Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight	The body weight change from baseline following 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: August 1, 2004
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: October 4, 2005
• First Submitted That Met QC Criteria: October 4, 2005
• First Posted (Estimate): October 6, 2005

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: Heart Failure; Edema; Tolvaptan; OPC-41061; Extracellular volume expansion
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Edema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: 156-03-001; JapicCTI-050038