Clinical Pharmacology Trial to Investigate the Dose of OPC-61815 Injection Equivalent to Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure

Study Overview
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Brief Summary
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The dose for intravenous administration of OPC-61815 achieving tolvaptan exposure equivalent to that for oral administration of tolvaptan 15-mg tablet will be investigated by administering OPC-61815 injection 2 to 16mg or tolvaptan 15-mg oral tablet to subjects with congestive heart failure.

Official Title
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A Multicenter, Double-blind, Randomized, Active-controlled, Parallel-group Comparison Clinical Pharmacology Trial to Investigate the Dose of OPC-61815 Injection Equivalent to Tolvaptan 15-mg Tablet in Patients With Congestive Heart Failure

Conditions
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Congestive Heart Failure

Intervention / Treatment
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* Drug: OPC-61815 injection 2mg
* Drug: OPC-61815 injection 4mg
* Drug: OPC-61815 injection 8mg
* Drug: OPC-61815 injection 16mg
* Drug: Tolvaptan tablet 15mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects 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 Subjects with congestive heart failure in whom lower limb edema, pulmonary congestion, and/or jugular venous distension due to volume overload is present Subjects who are currently hospitalized or who are able to be hospitalized during the trial Exclusion Criteria: Subjects with acute heart failure Subjects with a history of hypersensitivity to any of ingredients of OPC-61815 or tolvaptan Subjects who are unable to sense thirst or who have difficulty with fluid intake

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPC-61815 injection 2mg<br>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg. | Drug: OPC-61815 injection 2mg<br>* Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 2 mg.<br>|
| Experimental: OPC-61815 injection 4mg<br>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg. | Drug: OPC-61815 injection 4mg<br>* Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 4 mg.<br>|
| Experimental: OPC-61815 injection 8mg<br>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg. | Drug: OPC-61815 injection 8mg<br>* Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 8 mg.<br>|
| Experimental: OPC-61815 injection 16mg<br>Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg. | Drug: OPC-61815 injection 16mg<br>* Once daily for 5 days placebo tablet will be orally administered, followed immediately by intravenous administration of OPC-61815 at 16 mg.<br>|
| Active Comparator: Tolvaptan tablet 15mg<br>Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo. | Drug: Tolvaptan tablet 15mg<br>* Once daily for 5 days tolvaptan 15-mg tablet will be orally administered, followed immediately by 1-hour intravenous administration of placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of OPC-41061 on Day 1 |  | Baseline, 1, 1.5, 2, 4, 6, 12 24 hours after the start of administration of investigational drug | 
| Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC24h) on Day 1 |  | Baseline, 1, 1.5, 2, 4, 6, 12 24 hours after the start of administration of investigational drug |