Short-Term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01336972
First received: April 15, 2011
Last updated: December 5, 2012
Last verified: December 2012

April 15, 2011
December 5, 2012
October 2010
November 2011   (final data collection date for primary outcome measure)
Pharmacodynamics: measured glomerular filtration rate (GFR), effective renal plasma flow (ERPF),and filtration fraction (GFR/ERPF) [ Time Frame: Final Treatment Visit (after approximately 3 weeks), Post Treatment Visit (3 weeks off treatment) ] [ Designated as safety issue: Yes ]
Change from baseline in measured GFR (as determined by iothalamate clearance), ERPF (as determined by hippuran clearance) and filtration fraction(GFR/ERPF).
Same as current
Complete list of historical versions of study NCT01336972 on ClinicalTrials.gov Archive Site
  • Pharmacodynamics: Free water clearance [ Time Frame: Final Treatment Visit (after approximately 3 weeks), Post Treatment Visit (3 weeks off treatment) ] [ Designated as safety issue: No ]
    Change from baseline at steady-state and follow-up in free water clearance.
  • Pharmacokinetics [ Time Frame: Final Treatment Visit (after approximately 3 weeks), Post Treatment Visit (3 weeks off treatment) ] [ Designated as safety issue: No ]
    The maximal (peak) plasma concentration (Cmax), time to Cmax (tmax) and area under the concentration-time curve from time 0 to the time of the last measurable concentration (AUCt) of tolvaptan in plasma.
  • Total kidney volume [ Time Frame: Final Treatment Visit (after approximately 3 weeks), Post Treatment Visit (3 weeks off treatment) ] [ Designated as safety issue: No ]
    Short-term changes in total kidney volume (TKV) as percent change from baseline measured by MRI.
Same as current
Not Provided
Not Provided
 
Short-Term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
A Phase 2a, Single-Center Study Investigating the Short-Term Renal Hemodynamic Effects, Safety and Pharmacokinetics/ Pharmacodynamics of Oral Tolvaptan in Subjects With ADPKD at Various Stages of Renal Function

The purpose of the trial is to determine the short-term effects of dose regimens of tolvaptan studied in patients with autosomal dominant polycystic kidney disease (ADPKD) at various levels of renal function.

This trial will characterize the effects of tolvaptan at steady-state in subjects with eGFR(Estimated Glomerular Filtration Rate

) >60, 60-30 and <30 mL/min*1.73 m2 and is designed to provide data to support the continued use or new introduction of tolvaptan in subjects with renal impairment due to ADPKD.

Subjects titrated to the highest possible split-dose of tolvaptan used in studies with ADPKD patients will be assessed for the actions of the drug on renal hemodynamics, pharmacokinetic and pharmacodynamic parameters in subjects with various levels of renal function. The reversibility of changes after withdrawal of the drug will be determined. Acute transitory effects on kidney volume will also be explored.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Autosomal Dominant Polycystic Kidney Disease
Drug: tolvaptan
Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability.
Other Name: OPC-41061
  • Experimental: Group A
    eGFR > 60 ml/min/1.73m2
    Intervention: Drug: tolvaptan
  • Experimental: Group B
    eGFR 60-30 ml/min/1.73m2
    Intervention: Drug: tolvaptan
  • Experimental: Group C
    eGFR <30 ml/min/1.73m2
    Intervention: Drug: tolvaptan
Boertien WE, Meijer E, de Jong PE, Bakker SJ, Czerwiec FS, Struck J, Oberdhan D, Shoaf SE, Krasa HB, Gansevoort RT. Short-term renal hemodynamic effects of tolvaptan in subjects with autosomal dominant polycystic kidney disease at various stages of chronic kidney disease. Kidney Int. 2013 Dec;84(6):1278-86. doi: 10.1038/ki.2013.285. Epub 2013 Jul 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
29
November 2011
November 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of ADPKD by Ravine criteria

Exclusion Criteria:

  • Renal replacement therapy
  • Use of therapies for the purpose of affecting PKD cysts
  • Evidence of significant renal disease, eg active glomerular nephritidies, renal cancer, single kidney
  • Significant risk-factors for renal impairment, eg chronic use of diuretics, advanced diabetes, use of nephrotoxic drugs
  • History of significant coagulation defects or hemorrhagic diathesis
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01336972
156-09-284, 2010-019025-33
No
Otsuka Pharmaceutical Development & Commercialization, Inc.
Otsuka Pharmaceutical Development & Commercialization, Inc.
Not Provided
Study Director: Frank Czerwiec, MD, PhD Otsuka Pharmaceutical Development & Commercialization, Inc.
Principal Investigator: Ron T Gansevoort, MD University Medical Centre Groningen
Otsuka Pharmaceutical Development & Commercialization, Inc.
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP