Clinical trial NCT06795399: A Proof-of-concept Trial for OPC 131461 in Patients Hospitalized for Worsening Heart Failure
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Heart Failure
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-28
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Proportional Change From Baseline in Serum Concentration of NT-proBNP at Day 31
timeFrame: Baseline, Day 31
Secondary outcomes:
measure: Proportional Change From Baseline in Serum Concentration of NT-proBNP at Days 8 and 15
timeFrame: Baseline, Days 8 and 15
measure: Time to First Heart Failure (HF) Rehospitalization
timeFrame: From first dose of study drug up to end of treatment period (up to 30 days)
measure: Time to First Urgent HF Outpatient Visit
timeFrame: From first dose of study drug up to end of treatment period (up to 30 days)
measure: Time to Cardiovascular (CV) Death
timeFrame: From first dose of study drug up to end of treatment period (up to 30 days)
measure: Composite Endpoint Defined by the Win Ratio
timeFrame: From the first dose of the study drug up to end of treatment period (up to 30 days)
measure: Change From Baseline in Kansas City Cardiomyopathy Questionnaire - 23 items (KCCQ-23) Clinical Summary Score
timeFrame: Up to 31 days
measure: Change From Baseline in KCCQ-23 Total Symptom Score
timeFrame: Up to 31 days
measure: Change From Baseline in KCCQ-23 Physical Limitations Score
timeFrame: Up to 31 days
measure: Change From Baseline in Body Weight
timeFrame: Up to 37 days
measure: Change From Baseline in EVEREST Congestion Score
timeFrame: Up to 37 days
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Up to 37 days
measure: Number of Participants With Serum Electrolyte Abnormalities
timeFrame: Up to 37 days
measure: Number of Participants With Hypotension/Orthostatic Hypotension and Related Treatment-emergent Adverse Events (TEAEs) of Syncope and Presyncope
timeFrame: Up to 37 days
measure: Number of Participants With Major and Minor Bleeding Events
timeFrame: Up to 37 days
Other outcomes:
Locations:
Study officials:
References: