Autosomal Dominant Polycystic Kidney Disease （ADPKD)
Conditions
Brief summary
ADPKD patients who enrolled in Trial 156-04-251 will receive repeated oral administration of tolvaptan twice daily (morning and evening: 45mg/15mg, 60mg/30mg, or 90mg/30mg).
Interventions
DRUGtolvaptan
Repeated oral administration twice daily (morning and evening) at one of three split dose-regimens 45mg/15mg, 60mg/30mg or 90mg/30mg.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
23 Years to 53 Years
Healthy volunteers
No
Inclusion criteria
* Patients who participated in Trial 156-04-251 in Japan and for whom CRF collection has been completed. * Patients who completed 3-year repeated administration and who completed the second follow-up visit or patients whose treatment with the trial drug was interupted due to pregnancy and who completed out the second follow-up visit in Trial 156-04-251. * Patients in whom any adverse events occurring in Trial 156-04-251 were resolved orstabilized and require no further follow-up.
Exclusion criteria
* Patients with eGFR of less than 15 mL/min/1.73 m2 * Pregnant, breast-feeding, or possibly pregnant women or women who are planning to become pregnant * Patients who received any investigational drug other than Tolvaptan within 30 days prior to commencement of administration of tolvaptan * Any patients who, in the opinion of the principle investigator or subinvestigators, should not participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Kidney Volume | Baseline, Month12, Month24, and Month36 | Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period. Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded. |
| Renal Function Test (eGFR) | Baseline, Month12, Month24, and Month36 | Estimated glomerular filtration rate calculated by Japanese equation for eGFR during trial period. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded. |
| Renal Function Test (Cys-C) | Baseline, Month 12, Month 24, and Month 36 | Measured values of serum cystatin C concentration during trial period. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tolvaptan Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg | 135 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | eGFR under the withdrawal criteria | 7 |
| Overall Study | No tolerability for the lowest dose | 2 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Tolvaptan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 135 Participants |
| Age, Continuous | 42.7 years STANDARD_DEVIATION 5.9 |
| Region of Enrollment Japan | 135 participants |
| Sex: Female, Male Female | 77 Participants |
| Sex: Female, Male Male | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 135 |
| other Total, other adverse events | 134 / 135 |
| serious Total, serious adverse events | 20 / 135 |
Outcome results
Primary
Renal Function Test (Cys-C)
Measured values of serum cystatin C concentration during trial period. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded.
Time frame: Baseline, Month 12, Month 24, and Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Renal Function Test (Cys-C) | 1.016 mg/L | Standard Deviation 0.421 |
| Month 12 | Renal Function Test (Cys-C) | 1.114 mg/L | Standard Deviation 0.477 |
| Month 24 | Renal Function Test (Cys-C) | 1.129 mg/L | Standard Deviation 0.466 |
| Month 36 | Renal Function Test (Cys-C) | 1.281 mg/L | Standard Deviation 0.461 |
Primary
Renal Function Test (eGFR)
Estimated glomerular filtration rate calculated by Japanese equation for eGFR during trial period. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded.
Time frame: Baseline, Month12, Month24, and Month36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Renal Function Test (eGFR) | 61.2 mL/min/1.73 m2 | Standard Deviation 21.7 |
| Month 12 | Renal Function Test (eGFR) | 56.3 mL/min/1.73 m2 | Standard Deviation 21.7 |
| Month 24 | Renal Function Test (eGFR) | 51.8 mL/min/1.73 m2 | Standard Deviation 20.1 |
| Month 36 | Renal Function Test (eGFR) | 43.5 mL/min/1.73 m2 | Standard Deviation 20.3 |
Primary
Total Kidney Volume
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period. Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded.
Time frame: Baseline, Month12, Month24, and Month36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Total Kidney Volume | 1812.38 mL | Standard Deviation 859.21 |
| Month 12 | Total Kidney Volume | 1878.82 mL | Standard Deviation 950.6 |
| Month 24 | Total Kidney Volume | 1934.14 mL | Standard Deviation 926.79 |
| Month 36 | Total Kidney Volume | 2214.28 mL | Standard Deviation 842.87 |