A Trial to Investigate the Efficacy and Safety of Orally Administered Tolvaptan (OPC-41061) in Patients With Chronic Renal Failure Undergoing Hemodialysis or Hemodiafiltration

Study Overview
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Brief Summary
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This is a study to investigate the efficacy and safety of OPC-41061 by 24-week oral administration of OPC-41061 at 15-mg or 30-mg or placebo in patients with chronic renal failure who are undergoing hemodialysis or hemodiafiltration and who have daily urine volume of at least 500 mL/day.

Official Title
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A Phase 2, Multicenter, Placebo-controlled, Double-blind, Randomized, Parallel-group Trial to Investigate the Efficacy and Safety of Orally Administered Tolvaptan (OPC-41061) in Patients With Chronic Renal Failure Undergoing Hemodialysis or Hemodiafiltration

Conditions
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Chronic Renal Failure

Intervention / Treatment
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* Drug: OPC-41061
* Drug: OPC-41061
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic renal failure requiring hemodialysis or hemodiafiltration 3 times a week Daily urine volume of ≥ 500 mL/day Male or female patients age 20 to 80 years, inclusive Use of one of the specified contraceptive methods until 4 weeks after final IMP administration Capable of providing their own written informed consent prior to any trial-related procedures being performed Exclusion Criteria: Patients with a complication of urinary impairment due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause Patients with NYHA class IV heart failure Patients with impaired hepatic function(chronic hepatitis, drug-induced liver injury) Patients with serious ischemic heart disease who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial Patients with serious arrhythmia who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial Patients with serious secondary hyperparathyroidism(intact parathyroid hormone > 500 pg/mL) Patients who are concomitantly undergoing peritoneal dialysis Patients with a history of cerebrovascular disease or coronary artery disease within 4 weeks prior to informed consent, a history of hypersensitivity to any ingredient of tolvaptan or benzazepine derivatives such as mozavaptan hydrochloride or a history of impaired hepatic function(chronic hepatitis, drug-induced liver injury) Patients with any of the following abnormal laboratory values: hemoglobin < 8.0 g/dL, total bilirubin > 3.0 mg/dL, ALT (GPT) or AST (GOT) > 2 times the upper limit of the reference range, serum sodium > upper limit of the reference range, serum sodium < 125 mEq/L, or serum potassium > 6.0 mEq/L Patients who are unable to sense thirst or who have difficulty with fluid intake Patients who have received OPC-41061 in history. Participation in any other clinical trial or post-marketing clinical study within 4 weeks prior to informed consent for the present trial Female patients who are pregnant, possibly pregnant, or nursing Patients otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPC-41061 15mg/day<br>Will be orally administered once daily after breakfast on all days on which subjects do not undergo dialysis. OPC-41061 at 15 mg/day will be administered for 24 week. | Drug: OPC-41061<br> <br> * Other names: Tolvaptan;|
| Experimental: OPC-41061 30mg/day<br>Will be orally administered once daily after breakfast on all days on which subjects do not undergo dialysis. OPC-41061 at 15 mg/day will be administered for 1 week and then OPC-41061 30 mg/day for 23 weeks | Drug: OPC-41061<br> <br> * Other names: Tolvaptan;|
| Placebo Comparator: Placebo<br>Will be orally administered once daily after breakfast on all days on which subjects do not undergo dialysis. Placebo will be administered for 24 week. | Drug: Placebo<br> <br> * Other names: Blank Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Daily Urine Volume | Change in daily urine volume from baseline to the end of the treatment was calculated using descriptive statistics. | Baseline，End of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Volume of Fluid Removed by Dialysis Per Week | Change in total volume of fluid removed by dialysis per week from baseline to the end of the treatment was calculated using descriptive statistics. | Baseline，End of the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Undergoing Hemodialysis, Undergoing Hemodiafiltration