Autosomal Dominant Polycystic Kidney Disease (ADPKD) MedDRA version: 17.0 Level: LLT Classification code 10036046 Term: Polycystic kidney, autosomal dominant System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Samsca 15 mg tablets
Product Name: Tolvaptan 15 mg tablets
Product Code: OPC-41061
Pharmaceutical Form: Tablet
INN or Propos
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Successful completion (protocol defined completer without early termination) of a previous Phase 1, 2, or 3 tolvaptanADPKD or renal impairment trial, with a confirmed diagnosis of ADPKD (unless approved by the sponsor and medical monitor). If early termination from the previous trial was due to exceptional circumstances, reinitiation of tolvaptan is judged to be safe, and participation is approved by the sponsor and medical monitor, subjects may be enrolled beginning in January 2012. 2) Estimated GFR = 30 mL/min/1.73m2 within 45 days prior to the baseline visit (calculated using the IDMS-traceable modification of diet in renal disease [4 parameter MDRD] equation with correction for gender and race). Subjects with lower estimated GFR (eGFR) 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: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 750 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 750
Exclusion criteria
Exclusion criteria: Trial Entry Exclusion Criteria 1) Inability to provide written informed consent. 2) Women of childbearing potential, or their partners, who will not adhere to the reproductive precautions as outlined in the Informed Consent form. 3) Positive urine pregnancy test (women only) 4) Subjects who are pregnant or breast-feeding. 5) Inability to take oral medications. 6) Subjects who have clinically significant allergic reactions to tolvaptan or chemically related structures such as benzazepines (benzazepril, conivaptan, fenoldopam mesylate or mirtazapine). 7) Subjects having disorders in thirst recognition or inability to access fluids. 8) Subjects with critical electrolyte imbalances, as determined by the investigator. 9) Subjects with or at risk of significant hypovolemia, as determined by investigator. 10)Subjects with clinically significant anemia, as determined by investigator. 11)Subjects with a history of substance abuse (within the last 3 years). 12)Subjects taking other experimental (ie, non-marketed) therapies or current participation in another clinical drug or device trial. Current participation in the off-drug follow up period of another ADPKD trial with tolvaptan is permitted. Efficacy Analysis Exclusion Criteria 13)Subjects having contraindications to, or interferance with MRI assessments (eg, ferro-magnetic prostheses, ancurysm clips, severe claustrophobia). 14)Subjects with a history of taking a vasopressin antagonist, outside of previous participation in a tolvaptan trial. 15) Subjects with a history of persistant non-compliance with anti-hypertensive or other important medical therapy. 16)Subjects taking medications or having concomitant illnesses likely to confound endpoint assessments, including taking approved (ie, marketed) therapies for the purpose of affecting PKD cysts such as tolvaptan, vasopressin antagonists, anti-sense RNA therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin), and cyst reduction surgery. 17)Subjects with advanced diabetes (ie, those with poor glycemic control evidenced by a history of severly elevated hemoglobin AIC, or with evidence of advanced retinpathy, nephropathy or peripheral vascular disease due to micro-or-macro vascular disease).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate whether tolvaptan modifies ADPKD progression as measured by changes in endpoints of total kidney volume (TKV) and renal function. Disease modification is evidenced further by the non-inferiority of endpoint progression slope during this study for those receiving early, continuous treatment with tolvaptan, as compared to those with delayed treatment (ie, whose initial treatment was with placebo in trial 156-04-251). ; Secondary Objective: To determine whether, for placebo-treated subjects from trial 156-04-251, the annual rate of change (slope) in TKV and renal function changes during the crossover from placebo to tolvaptan treatment. To explore exposure response relationship among all subjects enrolled in this trial for changes in TKV, renal function and hypertension. ; Primary end point(s): In subjects randomized to tolvaptan and placebo in 156-04-251 and enrolled and treated in 156-08-271 as early treated and delayed treated groups: • Change from the 156-04-251 baseline in TKV at Month 24 of 156-08-271 ;Timepoint(s) of evaluation of this end point: Database lock Feb 2015 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In subjects randomized to tolvaptan and placebo in 156-04-251 and enrolled and treated in 156-08-271 as early treated and delayed treated groups: • Change from the 156-04-251 baseline in eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Month 24 of 156-08-271 • Slope of TKV of the 156-08-271 study • Slope of eGFR (CKD-EPI) of the 156-08-271 study Other Secondary Efficacy Endpoints: In prior placebo subjects enrolling from protocol 156-04-251: • Rate of change in annual TKV slope when crossing over from placebo to tolvaptan treatment • Rate of change in annual slope of renal function (eGFR CKD-EPI) when crossing over from placebo totolvaptan treatment For all subjects enrolled in this trial: • Change from baseline in TKV by exposure group • Change from end of titration in renal function (eGFRCKD-EPI) by exposure group ;Timepoint(s) of evaluation of this end point: Database lock Feb 2015 | — |
Countries
Argentina, Belgium, Canada, France, Germany, Italy, Netherlands, Poland, Romania, Russian Federation, United Kingdom, United States
Contacts
Public ContactMarita Lynott
MMG, Inc.
Outcome results
None listed