Chronic Renal Failure
Conditions
Keywords
Tolvaptan, dialysis
Brief summary
To investigate the efficacy, pharmacokinetics, pharmacodynamics, and safety of OPC-41061 in patients with chronic renal failure who are undergoing peritoneal dialysis, using daily urine volume, body weight, and edematous conditions as parameters and conducting dose escalation every 2 days until reaching the dose that achieves urine volume increase and then performing 5-day repeated administration at the fixed dose, the final dose used in the dose escalation period.
Interventions
DRUGOPC-41061
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with chronic renal failure * Patients who are undergoing peritoneal dialysis (continuous ambulatory peritoneal dialysis \[CAPD\]) * Patients who, after undergoing peritoneal dialysis, received any of the following medical treatments for fluid overload \[OR: hypervolemia\] that had insufficient effect: * Addition or increase of diuretics * Increase in concentration or volume of peritoneal dialysis fluid * Increase in the number of changes of peritoneal dialysis fluid * 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 * Subjects who are inpatients or who can be admitted to the trial site for the duration of the trial period
Exclusion criteria
* Subjects with any of the following diseases, complications, or symptoms: * Suspected hypovolemia * Daily urine volume less than 200 mL * Urination impaired due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause * Cardiac function of NYHA class 4 * 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 9.0 g/dL, total bilirubin higher than 3.0 g/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 125 mEq/L, or serum potassium higher than 5.5 mEq/L * Subjects with any of the following conditions, concomitant diseases, or symptoms: * defect in diaphragm * hemorrhagic diathesis due to uremia * suspected lactic acid metabolic disorder * suspected peritonitis, peritoneal damage, peritoneal adhesion, or disorders in intraabdominal organs * Subjects who have undergone peritoneal dialysis for 8 years or longer * Subjects who are scheduled to undergo hemodialysis or concomitant use of hemodialysis, or renal transplantation * Subjects who have participated in any other clinical trial or post-marketing clinical studies within 30 days prior to informed consent * Subjects who have previously received OPC-41061 * Subjects who are unable to sense thirst or who have difficulty with fluid or food intake * 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 in Daily Urine Volume From Baseline | Urine Volume on day13 minus Urine Volume at baseline(day9) on the repeated-administration period. | Change in daily urine volume from baseline during the repeated-administration period (For five days). |
| Percent Change in Daily Urine Volume From Baseline | 100%*<Urine Volume on day13 minus Urine Volume at baseline(day9) on the repeated-administration period/Urine Volume at baseline(day9) on the repeated-administration period> | Percent change in daily urine volume from baseline during the repeated-administration period (For five days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight From Baseline | Body weight on day13 minus Body weight at baseline(day9) on the repeated-administration period | Change in body weight from baseline during the repeated-administration period(For five days). |
| Percent Change in Body Weight | 100%*<Body weight on day13 minus Body weight at baseline (day9)/Body weight at baseline(day9)> | Percent change in body weight from baseline during the repeated-administration period(For five days). |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPC-41061 In the dose-escalation period,the dose of OPC-41061 was to be sequentially increased every 2 days as indicated below until daily urine volume of the OPC-41061 administration at each dose showed an crease of at least 500 mL from the pre-observation period. Dose escalation was to be terminated at the dose at which daily urine volume increased by 500 mL or more. If an increase in daily urine volume of at least 500 mL was not observed at the dose of 60 mg/day, the subject was to be withdrawn from the trial.
\- 7.5, 15, 30, 60 mg/day (up to a total of 8 days)
OPC-41061 was administered at a fixed dose (final dose administered in the dose-escalation period) once daily for 5 days on the repeated-administration period. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Protocol Violation | 10 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | OPC-41061 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 65.1 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment Japan | 20 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Change in Daily Urine Volume From Baseline
Change in daily urine volume from baseline during the repeated-administration period (For five days).
Time frame: Urine Volume on day13 minus Urine Volume at baseline(day9) on the repeated-administration period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 | Change in Daily Urine Volume From Baseline | 18.3 mL | Standard Deviation 340.2 |
Primary
Percent Change in Daily Urine Volume From Baseline
Percent change in daily urine volume from baseline during the repeated-administration period (For five days).
Time frame: 100%*<Urine Volume on day13 minus Urine Volume at baseline(day9) on the repeated-administration period/Urine Volume at baseline(day9) on the repeated-administration period>
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 | Percent Change in Daily Urine Volume From Baseline | 8.89 Percentage | Standard Deviation 33.2 |
Secondary
Change in Body Weight From Baseline
Change in body weight from baseline during the repeated-administration period(For five days).
Time frame: Body weight on day13 minus Body weight at baseline(day9) on the repeated-administration period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 | Change in Body Weight From Baseline | -0.61 kg | Standard Deviation 0.84 |
Secondary
Percent Change in Body Weight
Percent change in body weight from baseline during the repeated-administration period(For five days).
Time frame: 100%*<Body weight on day13 minus Body weight at baseline (day9)/Body weight at baseline(day9)>
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-41061 | Percent Change in Body Weight | -0.92 Percentage | Standard Deviation 1.31 |