A Proof-of-concept Trial for OPC 131461 in Patients Hospitalized for Worsening Heart Failure

A Phase 2, Randomized, Double-blind, Placebo-controlled, Proof of Concept Trial for OPC-131461 in Patients Hospitalized for Worsening Heart Failure With Laboratory Evidence of Incomplete Decongestion Following Urgent Decongestive Therapy

The primary objective of the study is to compare relative changes in blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels after 30 days of treatment in participants with worsening heart failure (WHF), who are treated with either OPC-131461 or placebo.

Study Overview

• Status: Withdrawn
• Conditions: Heart Failure
• Intervention / Treatment: Drug: OPC-131461; Drug: Placebo

Detailed Description

Each participant in this trial is expected to participate in the following periods of the trial:

• Screening/qualification period: up to 48 hours (2 days)
• Double-blind treatment period: 30 days
• Safety follow-up period: 7 days
• Vital status follow-up period: 6 months

Eligible participants will be randomized to receive the study drug (1 of 2 dose levels [5 milligrams (mg) or 10 mg] of OPC-131461 tablets or placebo) in a 1:1:1 ratio.

Overall, the trial duration is expected to be approximately 210 days (7 months).

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of HF ≥ 3 months prior to screening.
• Admitted to the hospital with primary diagnosis of WHF and received treatment with intravenous (IV) diuretics.
• Eligible participants will be randomized no earlier than 48 hours and up to 5 days after presentation to the hospital as long as they meet the following definition of stable status: Stable for at least 24 hours, defined by systolic blood pressure (SBP) ≥ 90 millimeters of mercury (mmHg) for preceding 24 hours, no increase in diuretic dose for 24 hours prior to randomization, did not receive IV inotropic or vasodilator (including nitrates) for 24 hours prior to randomization, and no oxygen therapy or mechanical ventilation in the 24 hours prior to randomization
• Left ventricular ejection fraction (LVEF) assessed either during hospitalization for Index Event or within 12 months prior to randomization.
• Has evidence of incomplete decongestion, indicated by NT-proBNP levels > 750 picograms per milliliter (pg/mL) (or > 1000 pg/mL if in atrial fibrillation). At hospital sites where NT proBNP test is unavailable at screening: B-type natriuretic peptide (BNP) > 375 pg/mL (or > 500 pg/mL if in atrial fibrillation).

Exclusion Criteria:

• Primary cause of WHF (Index Event) due to valvular heart disease (defined as severe aortic or primary mitral regurgitation, moderate or severe aortic stenosis, any mitral stenosis requiring surgical repair, or active endocarditis), congenital heart disease, hypertrophic obstructive cardiomyopathy, pulmonary embolism, Type I myocardial infarction, infection, severe anemia, exacerbation of chronic obstructive pulmonary disease (COPD), or sustained ventricular tachycardia, or bradycardia with sustained ventricular rate < 45 beats/minute.
• Duration of hospitalization for Index Event > 2 weeks at time of screening.
• End-stage HF requiring at the time of screening left ventricular assist device (LVAD), intra-aortic balloon pump (IABP) or any similar mechanical support.
• Cardiac surgery (coronary artery bypass grafting [CABG]), percutaneous coronary intervention (PCI), implantation of a cardiac device or cardiac mechanical support implantation within 30 days prior to randomization or planned during the study
• Severely impaired renal function eGFR < 25 milliliters per minute per 1.73-meter square (mL/min/1.73m^2).
• History of dialysis or kidney transplant.
• History of cirrhosis or noncirrhotic portal hypertension.
• Severe hyponatremia Sodium (Na) level < 125 mEq/L (milliequivalents per liter) or hypernatremia Na level > 145 mEq/L).
• Systolic blood pressure < 90 mmHg at screening.
• History of or current hepatitis or acquired immunodeficiency syndrome or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HCV), or human immunodeficiency virus (HIV) antibodies.
• History of any significant drug allergy or known or suspected hypersensitivity to any component of the study drug.
• Use of any investigational drug within 30 days prior to screening.
• History of serious mental disorders that, in the opinion of the investigator, would exclude the participant from participating in this trial.

Note: Other protocol-specified inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OPC-131461 5 mg; Participants will receive OPC-131461 5 mg, orally, once daily for 30 days.	Drug: OPC-131461; OPC-131461 will be administered as oral tablets.
Experimental: OPC-131461 10 mg; Participants will receive OPC-131461 10 mg, orally, once daily for 30 days.	Drug: OPC-131461; OPC-131461 will be administered as oral tablets.
Placebo Comparator: Placebo; Participants will receive OPC-131461 matched placebo, orally, once daily for 30 days.	Drug: Placebo; OPC-131461 matched placebo will be administered as oral tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportional Change From Baseline in Serum Concentration of NT-proBNP at Day 31	Proportional change from baseline in serum concentration of NT-proBNP is defined as the ratio of NT-proBNP at Day 31 over baseline.	Baseline, Day 31

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportional Change From Baseline in Serum Concentration of NT-proBNP at Days 8 and 15	Proportional change from baseline in serum concentration of NT-proBNP is defined as the ratio of NT-proBNP at Day 8 over baseline and at Day 15 over baseline.	Baseline, Days 8 and 15
Time to First Heart Failure (HF) Rehospitalization		From first dose of study drug up to end of treatment period (up to 30 days)
Time to First Urgent HF Outpatient Visit		From first dose of study drug up to end of treatment period (up to 30 days)
Time to Cardiovascular (CV) Death		From first dose of study drug up to end of treatment period (up to 30 days)
Composite Endpoint Defined by the Win Ratio	A hierarchical composite of CV death, number of HF rehospitalizations, number of urgent HF outpatient visits, time to first HF rehospitalization or urgent HF outpatient visit, and change from baseline in Kansas City Cardiomyopathy Questionnaire - 23 items (KCCQ-23) Total Symptom Score (difference larger or equal to 5) will be analyzed using the Win ratio method.	From the first dose of the study drug up to end of treatment period (up to 30 days)
Change From Baseline in Kansas City Cardiomyopathy Questionnaire - 23 items (KCCQ-23) Clinical Summary Score	The KCCQ-23 is a questionnaire consisting of 23 items to measure health status, symptoms, and quality of life in participants with heart failure. The KCCQ-23 consists of the following domains: Physical Limitation, Symptoms, Self-efficacy and knowledge, Quality of Life, Social Limitation. A functional status score is calculated from physical limitations and symptoms. The clinical summary score is derived from the functional status score, quality of life, and social limitations domains and range from 0-100. A higher score indicates fewer symptoms and better physical functioning, reflecting improved overall clinical status.	Up to 31 days
Change From Baseline in KCCQ-23 Total Symptom Score	The KCCQ-23 is a questionnaire consisting of 23 items to measure health status, symptoms, and quality of life in participants with heart failure. The KCCQ-23 consists of the following domains: Physical Limitation, Symptoms, Self-efficacy and knowledge, Quality of Life, Social Limitation. The total symptom score combines responses from the symptom frequency and symptom burden domains. Score ranges from 0-100, where higher scores indicate fewer symptoms and a better symptom experience.	Up to 31 days
Change From Baseline in KCCQ-23 Physical Limitations Score	The KCCQ-23 is a questionnaire consisting of 23 items to measure health status, symptoms, and quality of life in participants with heart failure. The KCCQ-23 consists of the following domains: Physical Limitation, Symptoms, Self-efficacy and knowledge, Quality of Life, Social Limitation. The Physical Limitation Score will assess the impact of HF on participants' ability to perform physical activities. Scores range from 0-100, with higher scores reflecting fewer physical limitations and better functional capacity.	Up to 31 days
Change From Baseline in Body Weight		Up to 37 days
Change From Baseline in EVEREST Congestion Score	The EVEREST Congestion Score will assess the severity of congestion in participants with HF. The score includes clinical signs and symptoms such as edema, dyspnea, orthopnea, jugular vein distention, rales, and fatigue. The total score ranges from 0-18, with a higher score indicating greater severity of congestion and a lower score reflecting less congestion and improvement in symptoms.	Up to 37 days
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)		Up to 37 days
Number of Participants With Serum Electrolyte Abnormalities		Up to 37 days
Number of Participants With Hypotension/Orthostatic Hypotension and Related Treatment-emergent Adverse Events (TEAEs) of Syncope and Presyncope		Up to 37 days
Number of Participants With Major and Minor Bleeding Events		Up to 37 days

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

Helpful Links

• Otsuka Clinical Trial Website:
• Otsuka Clinical Trial Transparency:

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2025
• Primary Completion (Actual): May 25, 2025
• Study Completion (Actual): May 25, 2025

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): January 28, 2025

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 351-201-00015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• 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. Small studies with less than 25 participants are excluded from data sharing.
• 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; CSR

Drug and device information, study documents

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