A Phase 2, Multi-center, Open-label, Dose-finding Trial to Investigate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of OPC-41061 in Patients With Chronic Renal Failure Undergoing Hemodialysis or Hemodiafiltration

Study Overview
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Brief Summary
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To investigate the safety, pharmacokinetics, pharmacodynamics, and efficacy of OPC-41061 in patients with chronic renal failure undergoing hemodialysis or hemodiafiltration using variables, such as daily urine volume and increase in interval body weights between hemodialysis or hemodiafiltration, in 4-day intermittant administration (excluding the days of hemodialysis or hemodiafiltration) at the dose fixed during the dose-escalation period

Official Title
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A Phase 2, Multi-center, Open-label, Dose-finding Trial to Investigate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with chronic renal failure who are undergoing hemodialysis or hemodiafiltration three times a week Subjects between the ages of 20 and 80, inclusive (at time of informed consent) Subjects who are inpatients or who can be admitted to the trial site for the duration of the trial period Subjects who, together with their partner, are able to practice one of the specified contraceptive methods until 4 weeks after the final trial drug administration Patients who are capable of providing written informed consent themselves before any trial-related procedures are performed Exclusion Criteria: Subjects with a complication of urinary impairment due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause Subject with daily urine volume less than 500 mL Subject with Cardiac function of NYHA class 4 Subjects with serious ischemic heart disease, who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial Subjects with serious arrhythmia, who are judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial Subjects who are concomitantly undergoing peritoneal dialysis Subjects with ascites due to cirrhosis or cancer, requring medical treatments Subjects with any of the following medical histories: History of cerebrovascular disorder or coronary artery disease within 4 weeks prior to informed consent History of hypersensitivity or idiosyncratic reaction to benzazepine derivatives such as mozavaptan hydrochloride or benazepril hydrochloride Subjects with any of the following abnormal laboratory values: Hemoglobin lower than 8.0 g/dL, total bilirubin higher than 3.0 mg/dL, ALT (GPT) or AST (GOT) 2 times the upper limit of the reference range of the trial site, serum sodium higher than the upper limit of the reference range of the trial site, serum sodium lower than 125mEq/L Subjects with serum potassium higher than 6.0mEq/L and abnormal findings inappropriate for inclusion in the trial are observed by 12-lead ECG Subjects who are unable to sense thirst or who have difficulty with fluid or food intake Subjects who have participated in any other clinical trial or post-marketing clinical studies within 4 weeks prior to informed consent Female subjects who are pregnant, possibly pregnant, or nursing, or who plan to become pregnant during the trial period Subjects 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPC-41061<br> | Drug: OPC-41061<br>* The maximum number of days of administration will be 8 days (8 doses) in total 4 days each in the dose-escalation period and intermittant administration period. The investigational medicinal product (IMP) will be administered once daily after breakfast<br>|

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 | The daily urine volume at each timepoint and its change and the percent change from baseline will be summarized with descriptive statistics (number, mean, standard deviation [SD], minimum, median, maximum [same for following parameters]). | Baseline and Day 14 (Intermittent Administration Period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Fluid Removal Per Week by Dialysis | The total volume of fluid removed per week by dialysis at each timepoint and its change from baseline will be summarized with descriptive statistics. | Baseline (pretreatment observation period) and Intermittent Administration Period (Day 10 to Day 15) |