Chronic Renal Failure
Conditions
Brief summary
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
Interventions
DRUGOPC-41061
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
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daily Urine Volume | Baseline and Day 14 (Intermittent Administration Period) | 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 \[same for following parameters\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Fluid Removal Per Week by Dialysis | Baseline (pretreatment observation period) and Intermittent Administration Period (Day 10 to Day 15) | The total volume of fluid removed per week by dialysis at each timepoint and its change from baseline will be summarized with descriptive statistics. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPC-41061 Dose-titration period Administration of OPC-41061 will be started at 7.5 mg/day and the dose was increased stepwise up to as high as 60 mg/day until the dose for intermittent administration is determined. (If the dose was not fixed, the subject received the next higher dose following a 6-day washout period.) Intermittent administration period Subjects received once-daily 4-day intermittent administration of OPC-41061 (days on which hemodialysis or hemodiafiltration was not performed). | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 5 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | OPC-41061 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 60.4 years STANDARD_DEVIATION 12.5 |
| Region of Enrollment Japan | 23 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 13 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
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 \[same for following parameters\]).
Time frame: Baseline and Day 14 (Intermittent Administration Period)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 | Change From Baseline in Daily Urine Volume | 481.0 ml | Standard Deviation 427.1 |
Secondary
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.
Time frame: Baseline (pretreatment observation period) and Intermittent Administration Period (Day 10 to Day 15)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 | Change From Baseline in Total Fluid Removal Per Week by Dialysis | -1425.0 ml | Standard Deviation 2139.7 |