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Open-Label Tolvaptan Study in Subjects With ADPKD (TEMPO 4/4)

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ClinicalTrials.gov Identifier: NCT01214421
Recruitment Status : Completed
First Posted : October 5, 2010
Last Update Posted : May 25, 2018
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary:
To demonstrate whether tolvaptan modifies ADPKD progression as measured by changes from baseline (from trial 156-04-251) in total kidney volume (TKV) and renal function.

Condition or disease Intervention/treatment Phase
Autosomal Dominant Polycystic Kidney Disease (ADPKD) Drug: Tolvaptan Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1083 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multi-center, Open-label, Extension Study to Evaluate the Long-term Efficacy and Safety of Oral Tolvaptan Tablet Regimens in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Study Start Date : May 2010
Actual Primary Completion Date : February 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
Drug Information available for: Tolvaptan

Arm Intervention/treatment
Experimental: 251 Prior Tolvaptan

Tolvaptan tablets (as multiples of 15 or 30 mg) will be given orally twice daily until the last subject originating from the 156-04-251 trial who is eligible for efficacy analysis has completed the Month 24 visit. Dosing should occur on waking and approximately 9 hours later, irrespective of meals. Exact timing of dosing may be adjusted based on wake/sleep habits (eg, standard 8 AM and 5 PM may be switched to 10 PM and 7 AM if working a night shift). However, dosing times should be consistent for each individual's daily dose to maximize receptor suppression.Subjects should be titrated to the highest dose tolerated unless an equivalent dose was not tolerated and was associated with a significant adverse event in a prior trial. For example, the following titration schedule could be followed:

Day 0 - 45/15 mg split-dose regimen assigned Week 1 - tolerated dose, up-titrate to 60/30 mg Week 2 - tolerated dose, up-titrate to 90/30 mg Week 3 - tolerated dose, 90/30 mg continued.

Drug: Tolvaptan
Daily split-dose of tolvaptan titrated 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: 251 Prior Placebo
Subjects on Placebo from a previous open-label trial and not on tolvaptan at the baseline visit, initial dosing will commence with the lowest dose regimen and up-titrated to the last tolerated dosing regimen (as explained above).
Drug: Tolvaptan
Daily split-dose of tolvaptan titrated 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: Other Prior Study
For subjects enrolling from a previous open-label trial and are on tolvaptan at the baseline visit, initial dose assignment will remain consistent with the dose regimen the subject is currently on. Should a subject enroll from a previous open-label trial and not be on tolvaptan at the baseline visit, initial dosing will commence with the lowest dose regimen and up-titrated to the last tolerated dosing regimen (as explained above).
Drug: Tolvaptan
Daily split-dose of tolvaptan titrated 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




Primary Outcome Measures :
  1. Percent Change in Total Kidney Volume (TKV) [ Time Frame: 24 months ]
    For subjects continuing from protocol 156-04-251: change from 251 baseline TKV at month 24 of 156-08-271 comparing those previously treated with tolvaptan to those previously treated with placebo


Secondary Outcome Measures :
  1. Change in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: 24 months ]
    For subjects randomized to tolvaptan and placebo in 156-04-251 and enrolled and treated in 156-08-271 as early treated and delayed treatment groups: change from 251 baseline eGFR at month 24 of 156-08-271

  2. Slope of Total Kidney Value (TKV) [ Time Frame: 24 months ]
    For subjects randomized to tolvaptan and placebo in 156-04-251 and enrolled and treated in 156-08-271 as early treated and delayed treatment groups

  3. Slope of eGFR (CKD-EPI) [ Time Frame: 24 months ]
    For subjects randomized to tolvaptan and placebo in 156-04-251 and enrolled and treated in 156-08-271 as early treated and delayed treatment groups



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects who have successfully completed a Phase 1, 2, or 3 tolvaptan ADPKD or renal impairment trial, with a confirmed diagnosis of ADPKD

Exclusion Criteria:

  • Subjects unable to provide written informed consent
  • Subjects (men or women) who will not adhere to the reproductive precautions as outlined in the Informed Consent Form
  • Subjects (women only) with a positive urine pregnancy test
  • Subjects who are pregnant or breast-feeding
  • Subjects unable to take oral medications
  • Subjects who have allergic reactions to tolvaptan or chemically related structures such as benzazepines (benzazepril, conivaptan, fenoldopam mesylate or mirtazapine)
  • Subjects who have disorders in thirst recognition or an inability to access fluids
  • Subjects with critical electrolyte imbalances, as determined by the investigator
  • Subjects with or at risk of significant hypovolemia, as determined by investigator
  • Subjects with anemia, as determined by investigator
  • Subjects with a history of substance abuse (within the last 3 years)
  • 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
  • Subjects unable to complete MRI assessments(eg, subjects with ferro-magnetic prostheses, aneurysm clips, severe claustrophobia)
  • Subjects who have taken a vasopressin antagonist (outside of previous participation in a tolvaptan trial)
  • Subjects unable to comply with anti-hypertensive or other important medical therapy
  • Subjects with advanced diabetes
  • Subjects taking medications or having an illness that could confound endpoint assessments (including taking approved therapies for the purpose of affecting PKD cysts)

Information from the National Library of Medicine

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): NCT01214421


  Show 99 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Frank Czerwiec, MD, PhD Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01214421     History of Changes
Other Study ID Numbers: 156-08-271
2010-018401-10 ( EudraCT Number )
First Posted: October 5, 2010    Key Record Dates
Last Update Posted: May 25, 2018
Last Verified: May 2018

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Kidney Disease
ADPKD
Autosomal Dominant Polycystic Kidney Disease
Adult Polycystic Kidney Disease

Additional relevant MeSH terms:
Kidney Diseases, Cystic
Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Tolvaptan
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs