A Dose-ranging Trial of OPC-131461 in Cardiac Edema (Congestive Heart Failure [CHF])

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Doseranging Trial of OPC-131461 in Cardiac Edema (Congestive Heart Failure [CHF])

To investigate the dose response in respect of weight decrease following repeated oral administration of OPC-131461 at 1, 2, 5, and 10 mg or placebo in patients with CHF with volume overload despite having received diuretics other than vasopressin antagonists

Study Overview

• Status: Completed
• Conditions: Cardiac Edema (CHF)
• Intervention / Treatment: Drug: OPC 131461 10mg group; Drug: OPC 131461 5mg group; Drug: OPC 131461 2mg group; Drug: OPC 131461 1mg group; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Harasanshin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with CHF with lower limb edema, pulmonary congestion, or jugular venous distension due to volume overload.

• Subjects undergoing any of the following diuretic therapies

  • Loop diuretics at a dosage equivalent to 40 mg/day or more of furosemide tablet/fine granule
  • Concomitant administration of a loop diuretic and a thiazide diuretic (including similar drugs) at any doses
  • Concomitant administration of a loop diuretic and a mineralocorticoid receptor antagonist or potassium-sparing diuretic at any doses
• Subjects who were currently hospitalized or who are able to be hospitalized

Exclusion Criteria:

• Subjects with acute heart failure
• Subjects with an assisted circulation device
• Subjects who cannot sense thirst or who have difficulty in ingesting water

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo tablet	Drug: Placebo; Placebo tablet，once-daily oral administration for 14 days
Experimental: OPC 131461 10mg group; OPC-131461 5 mg tablet ｘ 2	Drug: OPC 131461 10mg group; OPC-131461 5 mg tablet x 2，once-daily oral administration for 14 days
Experimental: OPC 131461 5mg group; OPC-131461 5 mg tablet and placebo tablet	Drug: OPC 131461 5mg group; OPC-131461 5 mg tablet and placebo tablet，once-daily oral administration for 14 days
Experimental: OPC 131461 2mg group; OPC-131461 1 mg tablet ｘ 2	Drug: OPC 131461 2mg group; OPC-131461 1 mg tablet x 2，once-daily oral administration for 14 days
Experimental: OPC 131461 1mg group; OPC-131461 1 mg tablet and placebo tablet	Drug: OPC 131461 1mg group; OPC-131461 1 mg tablet and placebo tablet，once-daily oral administration for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 8	Calculate the change in body weight from the baseline up to Day 8 (kg)	Baseline, Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight From Baseline to Last Assessment Time Point (the Day After IMP Administration) by Day 15	Calculate the percentage change in body weight from the baseline up to last assessment time point (the day after IMP administration) by Day 15 （％）	Baseline, Day15
Improvement of or Change in Congestive Findings ( Lower Limb Edema ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7	The tibial margins or acrotarsia in a sitting position will be examined to assess the severity of edema according to the criteria in 0 : Absent, No pitting observed at all, 1:Mild,Slight pitting observed, 2:Moderate, Pitting observed, 3 : Severe,Apparent edema. Improvement rates (percentages of subjects who have symptoms at baseline and show markedly improved or improved after IMP administration) and resolution rates (percentages of subjects who have symptoms at baseline and no symptoms after IMP administration) at the last assessment time point (the day of IMP administration) by Day 7.	Baseline, Day7
Improvement of or Change in Congestive Findings ( Pulmonary Congestion ) From Baseline to Last Assessment Time Point (the Day of IMP Administration) by Day 7	The severity of pulmonary congestion will be determined according to the criteria in 0 : Absent, No congestion, 1:Mild,Pulmonary venous congestion, 2:Moderate, Interstitial pulmonary edema, 3 : Severe, Alveolar pulmonary edema. Improvement rates (percentages of subjects who have symptoms at baseline and show markedly improved or improved after IMP administration) and resolution rates (percentages of subjects who have symptoms at baseline and no symptoms after IMP administration) at the last assessment time point (the day of IMP administration) by Day 7.	Baseline, Day7

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Investigators: Study Director: Takeshi Tsunoda, Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2023
• Primary Completion (Actual): October 21, 2024
• Study Completion (Actual): October 21, 2024

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 7, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): October 20, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Edema; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Heart Failure; Edema, Cardiac; Population Characteristics; Demography; Population Groups
• Other Study ID Numbers: 351-102-00004; jRCT (Registry Identifier: jRCTs051200101)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No