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

Sponsor:	Otsuka Pharmaceutical Development & Commercialization, Inc.
Information provided by (Responsible Party):	Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:	NCT01336972

Purpose

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.

Condition	Intervention	Phase
Autosomal Dominant Polycystic Kidney Disease	Drug: tolvaptan	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Drug Information available for: Tolvaptan

U.S. FDA Resources

Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:

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).

Secondary Outcome Measures:

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.

Enrollment:	29
Study Start Date:	October 2010
Study Completion Date:	November 2011
Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group A eGFR > 60 ml/min/1.73m2	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 B eGFR 60-30 ml/min/1.73m2	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 C eGFR <30 ml/min/1.73m2	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

Detailed Description:

This trial will characterize the effects of tolvaptan at steady-state in subjects with eGFR >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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01336972

Locations

Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ

Sponsors and Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

Study Director:	Frank Czerwiec, MD, PhD	Otsuka Pharmaceutical Development & Commercialization, Inc.
Principal Investigator:	Ron T Gansevoort, MD	University Medical Centre Groningen

More Information

No publications provided

Responsible Party:	Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:	NCT01336972 History of Changes
Other Study ID Numbers:	156-09-284, 2010-019025-33
Study First Received:	April 15, 2011
Last Updated:	March 15, 2012
Health Authority:	Netherlands: Medical Ethics Review Committee (METC) United States: Food and Drug Administration

Additional relevant MeSH terms:

Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic

ClinicalTrials.gov processed this record on May 23, 2012