Efficacy of Tolvaptan on ADPKD Patients
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|ClinicalTrials.gov Identifier: NCT02729662|
Recruitment Status : Active, not recruiting
First Posted : April 6, 2016
Last Update Posted : June 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Autosomal Dominant Polycystic Kidney Disease||Drug: Tolvaptan||Not Applicable|
Based on the results of a study entitled "The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO 3:4) 1)," tolvaptan was approved in March 2014 for the treatment of autosomal dominant polycystic Kidney Disease (ADPKD) in Japan, followed by in other regions such as Europe and Canada.
In May 2014, Kyorin University Hospital started administration of tolvaptan to patients with ADPKD. In the clinical setting in which the dosing conditions differ from those in the TEMPO study, aspects that were not addressed in the TEMPO study may be investigated. The present study is a longitudinal clinical study to investigate the changes before and after administration of tolvaptan by employing a method different from that used in the TEMPO study in patients in whom the clinical course of the disease has been monitored since prior to the approval of tolvaptan.
The observation period (for a maximum duration of 3 years) of the study was originally planned to be completed on March 31, 2018 and the analyses of study results and the preparation of a research paper until September 2019. However, the study will be extended for another 2 years, because the long-term effects of the drug should be further investigated.
The indication approved in Japan defines the target population as those with an eGFR ≥15 mL/min/1.73 m2, but not specifies the upper limit of age. Therefore, the present study will permit the assessment of therapeutic effects of the drug in patients who are older or have more severe renal impairment as compared with in those participating in the TEMPO3:4 and 4.4 studies. Since such patients generally have a greater TKV, the study may also provide information to decide whether the efficacy of tolvaptan differs according to TKV. The present study is a single-arm longitudinal study, unlike the preceding studies that were placebo-controlled studies 1,2); therefore, tolvaptan may be evaluated from different perspectives.
Rationale of DNA analysis The association between pathogenic genotype and the effects of tolvaptan has been reported, but the impact of mutation site has not been cleared 2). Genetic analysis for polycystic kidney will be included in the study to decide whether the effects of tolvaptan is associated with mutation site as well as pathogenic genotype (PKD1, PKD2).
Validation of alpha as a HtTKV slope Assuming that TKV corrected for the height at the age at measurement (t years old), HtTKVt (mL/m), increases at a constant annual rate (α, %/ per year) and the HtTKV0 is 150 mL/m, the following equation will be satisfied: HtTKVt = 150 (1+α)t. The α value calculated from the equation will be used as an indicator for supplementarily assessing the effect of tolvaptan on HtTKV slope 5,6).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||118 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Longitudinal Efficacy and Safety Study of Tolvaptan on Autosomal Dominant Polycystic Kidney Disease Patients (LET-PKD Study)|
|Actual Study Start Date :||October 1, 2016|
|Estimated Primary Completion Date :||August 31, 2020|
|Estimated Study Completion Date :||September 30, 2021|
Patients with ADPKD
This analysis set consists of patients whose at least 2 TKV data are available both before and after taking tolvaptan.
Other Name: Samsca
- The percent change in TKV volumetrically [ Time Frame: once a year, up to study completion, an expected average of up to 5 years ]
To evaluate the efficacy, the percent change in TKV volumetrically measured by MRI (% per year) is to be compared before and after administering tolvaptan to the same patients. The evaluation will include stratified analyses by patient background variables and examination data obtained during treatment.
[Supplementary assessment of the primary outcome variable] Using HtTKV slope, α (% per year), calculated from the HtTKVt at t years old as an indicator, the effect of tolvaptan on HtTKV slope will be supplementarily assessed 5,6).
- The percent change in epidermal growth factor receptor (eGER) [ Time Frame: once a month, up to study completion, an expected average of up to 5 years ]The percent change in eGFR (mL/min/1.73 m2 per year) will be compared before and after administration for evaluation. The evaluation will include stratified analyses by patient background variables and examination data obtained during treatment.
- A number of adverse events during the study [ Time Frame: through study completion, an expected average of up to 5 years ]
The following events that occurred in subjects who received a medicinal product of Otsuka Pharmaceutical from the time of informed consent and in the time of the study completion will be recorded.
- Serious adverse event
- Non-serious adverse event
- Other safety information
- The efficacy of or response to tolvaptan will be evaluated. [ Time Frame: twice a year, up to study completion, an expected average of up to5 years ]Based on the data obtained from 24-hour urine collection (Urine volume, urinary protein, Na, K, Cl, UN, creatinine, NAG, β2-MG, albumin, urinary osmolality), blood tests (Na, K, Cl, Ca, IP, BUN, creatinine, eGFR, uric acid, total protein, albumin, globulin, total bilirubin, γ-GTP, AST, ALT, HDL-cholesterol, LDL-cholesterol, triglyceride, cystatin-C, serum osmolality, WBC, RBC, Hb, Ht, Plt, MCV, MCH, MCHC, Retic), inulin clearance, and TKV, the efficacy of or response to tolvaptan will be evaluated. The evaluation will include stratified analyses by patient background variables, and examination data obtained during treatment.
- The impact of tolvaptan on the correlation between inulin clearance and eGFR values [ Time Frame: once a month, up to study completion, an expected average of up to 5 months ]The correlation between inulin clearance and eGFR values obtained from the formulae to estimate eGFR will be investigated to elucidate the impact of tolvaptan on the correlation.
- The association between the result of DNA analysis and the effect of tolvaptan [ Time Frame: through study completion, an expected average of up to 5 years ]The association between the result of DNA analysis and the effect of tolvaptan will be analyzed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02729662
|Kyorin University Hospital|
|Mitaka, Tokyo, Japan, 181-8611|
|Principal Investigator:||Eiji Higashihara, MD||Kyorin University School of Medicine|