Chronic Renal Failure
Conditions
Keywords
Undergoing Hemodialysis, Undergoing Hemodiafiltration
Brief summary
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.
Interventions
DRUGOPC-41061
DRUGPlacebo
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daily Urine Volume | Baseline，End of the treatment | Change in daily urine volume from baseline to the end of the treatment was calculated using descriptive statistics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Volume of Fluid Removed by Dialysis Per Week | Baseline，End of the treatment | Change in total volume of fluid removed by dialysis per week from baseline to the end of the treatment was calculated using descriptive statistics. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPC-41061 15mg/Day OPC-41061 (15 mg/day) was orally administered once daily after breakfast on off-dialysis days for 24 weeks. | 40 |
| OPC-41061 30mg/Day OPC-41061 (30 mg/day) was orally administered once daily after breakfast on off-dialysis days for 24 weeks. | 40 |
| Placebo OPC-41061 placebo was orally administered once daily after breakfast on off-dialysis days for 24 weeks. | 44 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 2 |
| Overall Study | Met withdrawal criteria | 2 | 2 | 5 |
| Overall Study | Non-compliance with study drug | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | OPC-41061 30mg/Day | Placebo | OPC-41061 15mg/Day | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 22 Participants | 23 Participants | 59 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 22 Participants | 17 Participants | 65 Participants |
| Age, Continuous | 60.5 years STANDARD_DEVIATION 12.6 | 64.4 years STANDARD_DEVIATION 8.7 | 64.2 years STANDARD_DEVIATION 11 | 63.0 years STANDARD_DEVIATION 10.8 |
| Region of Enrollment Japan | 40 participants | 44 participants | 40 participants | 122 participants |
| Sex: Female, Male Female | 11 Participants | 40 Participants | 5 Participants | 56 Participants |
| Sex: Female, Male Male | 29 Participants | 4 Participants | 35 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 39 | 0 / 44 |
| other Total, other adverse events | 34 / 39 | 38 / 39 | 34 / 44 |
| serious Total, serious adverse events | 6 / 39 | 7 / 39 | 10 / 44 |
Outcome results
Primary
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.
Time frame: Baseline，End of the treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 15mg/Day | Change From Baseline in Daily Urine Volume | 169.2 mL | Standard Deviation 422.2 |
| OPC-41061 30mg/Day | Change From Baseline in Daily Urine Volume | 111.8 mL | Standard Deviation 557.7 |
| Placebo | Change From Baseline in Daily Urine Volume | -259.9 mL | Standard Deviation 463.8 |
Secondary
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.
Time frame: Baseline，End of the treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 15mg/Day | Change in Total Volume of Fluid Removed by Dialysis Per Week | 485.9 mL | Standard Deviation 1979.3 |
| OPC-41061 30mg/Day | Change in Total Volume of Fluid Removed by Dialysis Per Week | 375.4 mL | Standard Deviation 1721.8 |
| Placebo | Change in Total Volume of Fluid Removed by Dialysis Per Week | 1099.5 mL | Standard Deviation 2160.5 |