Clinical Trial: Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 3b, Two-part, Multicenter, One Year Randomized, Double-blind, Placebo-controlled Trial of the Safety, Pharmacokinetics, Tolerability, and Efficacy of Tolvaptan Followed by a Two Year Open-labe

Brief Summary: The primary objective of the study is to assess the long term safety of treatment with tolvaptan in children and adolescents with autosomal dominant polycystic kidney disease (ADPKD). The secondary objective is to assess the pharmacodynamics, pharmacokinetics, and efficacy of tolvaptan in the same subject population.

Detailed Summary:

Tolvaptan has been demonstrated to delay the decline of kidney function in adults with rapidly progressing ADPKD (CKD stages 1 to 3) as measured by estimated glomerular filtration rate (eGFR) and Total Kidney Volume (TKV).

This trial will be the first trial of tolvaptan in children and adolescents with ADPKD.

Subjects in this study will be randomly assigned to one of two groups in Phase A; tolvaptan or placebo. Participants will have an equal chance of being assigned to either treatment group and will be stratified by age and gender into the following cohorts:

  • Female subjects ages 12 to 14 years, inclusive
  • Female subjects ages 15 to 17 years, inclusive
  • Male subjects ages 12 to 14 years, inclusive
  • Male subjects ages 15 to 17 years, inclusive

Phase (A) of this study will last 12 months. After that time, all subjects who qualify will be assigned tolvaptan and will be treated with tolvaptan for 24 months (Phase B).

A qualified subject is defined as one who has completed Phase A on investigational medicinal product (IMP), is willing to continue in the trial, and who does not have any adverse events (AEs), which would require IMP discontinuation.

Participants in this study will be required to make monthly visits to the study clinic and will be closely monitored over the course of the study.


Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Current Primary Outcome:

  • Change from baseline in spot urine osmolality (pre-morning dose) [ Time Frame: After 1 week of daily dosing during Phase A ]
  • Change from baseline in specific gravity (pre-morning dose) [ Time Frame: After 1 week of daily dosing during Phase A ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Percent change from Phase A baseline in height-adjusted total kidney volume (htTKV) as measured by MRI [ Time Frame: at 12 months ]
  • 24-hour urine volume in mL [ Time Frame: After at least 1 month on study medication during Phase A ]
  • 24-hour fluid intake in mL [ Time Frame: After at least 1 month on study medication during Phase A ]
  • 24-hour fluid balance in mL [ Time Frame: After at least 1 month on study medication during Phase A ]
  • 24-hour fluid balance in mL [ Time Frame: At Week 1 during Phase A and Phase B ]
  • Change from baseline in renal function (eGFR by Schwartz formula) at each visit in Phase A [ Time Frame: At Week 1, Month 1, Month 6, Month 12 ]
  • Change from Phase B baseline in renal function (eGFR by Schwartz formula) [ Time Frame: At Week 1, Months 1, 6, 12, 18, 24 ]
  • Percent change from Phase B baseline in htTKV as measured by MRI [ Time Frame: at 12 months ]
  • Percent change from Phase B baseline in htTKV as measured by MRI [ Time Frame: at 24 months ]
  • Proportions of each Tanner Stage by gender compared to normative populations [ Time Frame: At baseline, 6 and 12 months during the placebo-controlled phase (Phase A) and every 6 months (up to 26, 52, 78 and 104 weeks) during the open-label extension (Phase B) ]
  • Proportions of each Tanner Stage by age compared to normative populations [ Time Frame: At baseline, 6 and 12 months during the placebo-controlled phase (Phase A) and every 6 months (up to 26, 52, 78 and 104 weeks) during the open-label extension (Phase B) ]
  • Description of changes from baseline for height in cm by gender and age [ Time Frame: at baseline, 6 and 12 months during the placebo-controlled phase (Phase A) and every 6 months (up to 26, 52, 78 and 104 weeks) during the open-label extension (Phase B) ]
  • Description of changes from baseline for weight in kilograms by gender and age [ Time Frame: at baseline, 6 and 12 months during the placebo-controlled phase (Phase A) and every 6 months (up to 26, 52, 78 and 104 weeks) during the open-label extension (Phase B) ]
  • Changes from baseline in creatinine [ Time Frame: up thru 14 days post last dose in Phase A or B, whichever completion is latter. ]
  • Changes from baseline in vital signs [ Time Frame: up thru 14 days post last dose in Phase A or B, whichever completion is latter. ]
  • Changes from baseline in liver function tests (LFTs) [ Time Frame: up thru 14 days post last dose in Phase A or B, whichever completion is latter. ]
  • Changes from baseline in rate of aquaretic AEs in placebo and tolvaptan [ Time Frame: up thru 14 days post last dose in Phase A or B, whichever completion is latter. ]
  • Pharmacodynamic (PD) endpoints of sodium, creatinine and free water clearances in mL/min [ Time Frame: After at least 1 month on study medication in Phase A ]


Original Secondary Outcome: Same as current

Information By: Otsuka Pharmaceutical Development & Commercialization, Inc.

Dates:
Date Received: September 15, 2016
Date Started: September 2016
Date Completion: October 2020
Last Updated: April 24, 2017
Last Verified: April 2017