Autosomal Dominant Polycystic Kidney Disease (ADPKD) MedDRA version: 20.0 Level: LLT Classification code 10036046 Term: Polycystic kidney, autosomal dominant System Organ Class: 100000004850
Conditions
Interventions
Product Name: Tolvaptan 15mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Tolvaptan
Current Sponsor code: OPC-41061
Other descriptiv
Sponsors
Otsuka Pharmaceutical Development & Commercialization,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects aged > 18 years with confirmed diagnosis of ADPKD (during participation in prior tolvaptan trials) who have - Completed and transferred from the double-blind Trial 156-13-210 (12-month period including post-treatment follow-up, regardless of whether this was on-treatment or off-treatment), or - Completed Trial 156-08-271 or a prior tolvaptan trial, or - Interrupted or discontinued treatment in a tolvaptan trial other than Trial 156-13-210. Subjects may be enrolled with the medical monitor approval, and additional close monitoring may be required at the beginning of the trial - Renal function will be assessed during screening by using historical laboratory values (in the last 30 days) for serum creatinine levels to calculate the estimated glomerular filtration rate (eGFR). The eGFR values will be estimated based on the Chronic Kidney Disease - Epidemiology (CKD-EPI) formula. 2. Estimated glomerular filtration rate > 20 mL/min/1.73 m2 (calculated using the CKD-EPI formula) within 45 days prior to the baseline visit. Subjects who have an eGFR between 15 and 19 mL/min/1.73 m2 may be permitted with documented medical monitor approval prior to enrollment. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Women of childbearing potential (WOCBP) who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of IMP. If employing birth control, 2 of the following precautions must be used: vasectomy of partner, tubal ligation, vaginal diaphragm, intrauterine device, birth control. 2. Women who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP. 3. Need for chronic diuretic use. 4. Hepatic impairment based on liver function abnormalities other than that expected for ADPKD with cystic liver disease during screening. 5. Subjects with contraindications to required trial assessments (contraindications to optional assessments, eg, MRI are not a limitation). 6. Subjects who, in the opinion of the investigator or medical monitor, have a medical history or medical finding inconsistent with safety or trial compliance. This includes prior evidence of significant hepatic injury deemed to be related to tolvaptan use.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate and describe the long-term safety of tolvaptan.;Secondary Objective: Not Applicable;Timepoint(s) of evaluation of this end point: Throughout Study up to end of treatment and follow up visit.; Primary end point(s): This trial will have no formal endpoints. Safety variables will be summarized by descriptive statistics, (eg, proportion, mean, median, standard deviation [SD], minimum, and maximum values). In general, summary statistics, including changes from baseline, will be provided for safety variables based on all available data. Safety endpoints will be as follows: - Adverse events - Vital signs - Clinical laboratory assessments - Serum transaminase elevations for frequency (2x, 3x, 5x and 10x ULN), time to onset, time to peak levels, time of offset ( 3x ULN and bilirubin, total (BT), > 2x ULN without alkaline phosphatase ? 2x ULN) - Serum sodium excursions above 145, 150, or 155 mmol/L or below 135, 130, or 125 mmol/L Pharmacokinetic Endpoints Tolvaptan metabolite DM-4103, tolvaptan, and other tolvaptan metabolite plasma concentrations. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Exploratory Endpoints - Polycystic kidney disease (PKD) outcomes survey - Medical resource utilization (office/emergency room healthcare visits, hospital admissions, procedures and therapies) and productive days lost due to PKD outcomes will be reported for subjects as part of the ADPKD outcomes survey (To be analyzed and reported separately from the clinical study report). - Urine and plasma biomarker concentrations in subjects with liver abnormalities - DNA (with separate consent) may be assessed in subjects with liver abnormalities ;Timepoint(s) of evaluation of this end point: Throughout Study up to end of treatment visit. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Mexico, Netherlands, Norway, Peru, Poland, Romania, Russian Federation, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactOlga Sergeyeva, MD, MPH
Otsuka Pharmaceutical Development & Commercialization, Inc.
Outcome results
None listed