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Efficacy and Safety Trial of OPC-61815 Injection Compared With Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure

Primary Purpose

Congestive Heart Failure

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
OPC-61815
Tolvaptan Tab 15 MG
Sponsored by
Otsuka Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congestive Heart Failure

Eligibility Criteria

20 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients who are currently on treatment with any of the following diuretics

    1. Loop diuretics equivalent to furosemide tablet or fine granules at a dose of 40 mg/day or higher
    2. Concomitant use of a loop diuretic and a thiazide diuretic (including thiazide analogs) at any dose
    3. Concomitant use of a loop diuretic and an aldosterone antagonist or potassium-sparing diuretic agent at any dose
  • Patients with congestive heart failure in whom lower limb edema, pulmonary congestion, and/or jugular venous distension due to volume overload is present
  • Patients who are currently hospitalized or who are able to be hospitalized during the trial

Exclusion Criteria:

  • Patients with acute heart failure
  • Patients who are on a ventricular assist device
  • Patients who are unable to sense thirst or who have difficulty with fluid intake

Sites / Locations

  • Saiseikai Kumamoto Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

OPC-61815 injection 16 mg

Tolvaptan tablet 15mg

Arm Description

Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg

Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo

Outcomes

Primary Outcome Measures

Change From Baseline in Body Weight
Change in body weight from baseline (before investigational medicinal product [IMP] administration on Day 1) at time of final IMP administration (day after final IMP administration). A negative change from baseline indicates improvement.

Secondary Outcome Measures

Improvement Rate for Lower Limb Edema and Pulmonary Congestion
The improvement rate was defined as the percentage of subjects in whom the symptom was present at baseline and it markedly improved or improved after IMP administration. Improvement category is a 4-point scale below: Markedly improved Improved Unchanged Deteriorated
Change From Baseline in Jugular Venous Distension and Hepatomegaly
Jugular Venous Distension: the presence of Jugular Venous Distension was checked, and if present, the height (in cm) from the sternal angle to the highest point of pulsation in the internal Jugular vein was measured with the subject in a semi-upright position. A negative change from baseline indicates improvement. Hepatomegaly: the presence of a palpable liver was checked, and if present, the width (distance from the right costal arch of the right chest, in cm) was measured. A negative change from baseline indicates improvement.
Percentage of Subjects Who Achieve Resolution of Pulmonary Rales and Third Cardiac Sound
Percentage of subjects in whom the symptom was present at baseline and disappeared after IMP administration was provided. The presence of pulmonary rales was checked by auscultation. The presence of cardiac third sound was checked by auscultation.
Improvement Rate for New York Heart Association (NYHA) Classification
NYHA classification assesses the severity of heart failure based on subjective symptoms as follows. Class I: No limitations of physical activity. Ordinary physical activity caused no undue fatigue, palpitation, dyspnea or anginal pain. Class II: Slight limitation of physical activity, comfortable at rest. Ordinary physical activity resulted in fatigue, palpitation, dyspnea or anginal pain. Class III: Marked limitation of physical activity, comfortable at rest. Less than ordinary physical activity caused fatigue, palpitation, dyspnea or anginal pain. Class IV: Inability to carry on any physical activity without discomfort. heart failure or anginal syndrome may have been present even at rest. If any physical activity was undertaken, discomfort was increased. Of the subjects with Class II or higher at baseline, the percentage of subjects whose NYHA classification stage at the time of final IMP administration improved by 1 or more grades was provided.

Full Information

First Posted
December 5, 2018
Last Updated
July 14, 2021
Sponsor
Otsuka Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03772041
Brief Title
Efficacy and Safety Trial of OPC-61815 Injection Compared With Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure
Official Title
A Multicenter, Double-blind, Randomized, Active-controlled, Parallel-group, Non-inferiority Trial to Evaluate the Efficacy and Safety of OPC-61815 Injection Compared With Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
January 16, 2019 (Actual)
Primary Completion Date
July 21, 2020 (Actual)
Study Completion Date
July 29, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To confirm the non-inferiority of OPC-61815 16-mg injection to tolvaptan 15-mg tablet using as the primary endpoint the change in body weight following 5-day intravenous administration of OPC-61815 16-mg injection or 5-day oral administration of tolvaptan 15-mg tablet to CHF patients with volume overload despite having received diuretics other than vasopressin antagonists

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congestive Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
294 (Actual)

8. Arms, Groups, and Interventions

Arm Title
OPC-61815 injection 16 mg
Arm Type
Experimental
Arm Description
Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg
Arm Title
Tolvaptan tablet 15mg
Arm Type
Active Comparator
Arm Description
Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo
Intervention Type
Drug
Intervention Name(s)
OPC-61815
Intervention Description
Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg
Intervention Type
Drug
Intervention Name(s)
Tolvaptan Tab 15 MG
Intervention Description
Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo
Primary Outcome Measure Information:
Title
Change From Baseline in Body Weight
Description
Change in body weight from baseline (before investigational medicinal product [IMP] administration on Day 1) at time of final IMP administration (day after final IMP administration). A negative change from baseline indicates improvement.
Time Frame
Baseline, Day 6
Secondary Outcome Measure Information:
Title
Improvement Rate for Lower Limb Edema and Pulmonary Congestion
Description
The improvement rate was defined as the percentage of subjects in whom the symptom was present at baseline and it markedly improved or improved after IMP administration. Improvement category is a 4-point scale below: Markedly improved Improved Unchanged Deteriorated
Time Frame
Baseline, Day 6
Title
Change From Baseline in Jugular Venous Distension and Hepatomegaly
Description
Jugular Venous Distension: the presence of Jugular Venous Distension was checked, and if present, the height (in cm) from the sternal angle to the highest point of pulsation in the internal Jugular vein was measured with the subject in a semi-upright position. A negative change from baseline indicates improvement. Hepatomegaly: the presence of a palpable liver was checked, and if present, the width (distance from the right costal arch of the right chest, in cm) was measured. A negative change from baseline indicates improvement.
Time Frame
Baseline, Day 6
Title
Percentage of Subjects Who Achieve Resolution of Pulmonary Rales and Third Cardiac Sound
Description
Percentage of subjects in whom the symptom was present at baseline and disappeared after IMP administration was provided. The presence of pulmonary rales was checked by auscultation. The presence of cardiac third sound was checked by auscultation.
Time Frame
Baseline, Day 6
Title
Improvement Rate for New York Heart Association (NYHA) Classification
Description
NYHA classification assesses the severity of heart failure based on subjective symptoms as follows. Class I: No limitations of physical activity. Ordinary physical activity caused no undue fatigue, palpitation, dyspnea or anginal pain. Class II: Slight limitation of physical activity, comfortable at rest. Ordinary physical activity resulted in fatigue, palpitation, dyspnea or anginal pain. Class III: Marked limitation of physical activity, comfortable at rest. Less than ordinary physical activity caused fatigue, palpitation, dyspnea or anginal pain. Class IV: Inability to carry on any physical activity without discomfort. heart failure or anginal syndrome may have been present even at rest. If any physical activity was undertaken, discomfort was increased. Of the subjects with Class II or higher at baseline, the percentage of subjects whose NYHA classification stage at the time of final IMP administration improved by 1 or more grades was provided.
Time Frame
Baseline, Day 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who are currently on treatment with any of the following diuretics Loop diuretics equivalent to furosemide tablet or fine granules at a dose of 40 mg/day or higher Concomitant use of a loop diuretic and a thiazide diuretic (including thiazide analogs) at any dose Concomitant use of a loop diuretic and an aldosterone antagonist or potassium-sparing diuretic agent at any dose Patients with congestive heart failure in whom lower limb edema, pulmonary congestion, and/or jugular venous distension due to volume overload is present Patients who are currently hospitalized or who are able to be hospitalized during the trial Exclusion Criteria: Patients with acute heart failure Patients who are on a ventricular assist device Patients who are unable to sense thirst or who have difficulty with fluid intake
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Osamu Sato
Organizational Affiliation
Otsuka Pharmaceutical Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Saiseikai Kumamoto Hospital
City
Kumamoto
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 https://clinical-trials.otsuka.com/contact-us
IPD Sharing URL
https://clinical-trials.otsuka.com/contact-us

Learn more about this trial

Efficacy and Safety Trial of OPC-61815 Injection Compared With Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure

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