Clinical Trial: A Trial of Tolvaptan in Children and Adolescent Subjects With Euvolemic and Hypervolemic Hyponatremia

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

Official Title: A Pilot Phase 3b,Multicenter,Randomized,Double-blind,Placebo-controlled Trial of the Safety,Efficacy,and Pharmacokinetics of Titrated Oral SAMSCA®(Tolvaptan) in Children and Adolescent Subjects W

Brief Summary: The purpose of this trial is to demonstrate that tolvaptan effectively and safely increases and maintains serum sodium concentrations in children and adolescent subjects with euvolemic or hypervolemic hyponatremia.

Detailed Summary:

The purpose of the study is to also assess tolvaptan's pharmacokinetics (PK) and its effect on fluid balance in children and adolescent subjects with euvolemic or hypervolemic hyponatremia. Subjects who are diagnosed with euvolemic or hypervolemic hyponatremia (serum sodium < 130 mEq/L [mmol/L]) that persists despite initial standard background therapy (eg, including fluid restriction) are eligible to be screened for participation in this trial. Subjects who demonstrate prior resistance to vasopressin antagonist therapy will be excluded. All potential subjects must be deemed by the investigator as likely to benefit from a therapy that raises serum sodium levels.

Subjects will be required to be in a hospital setting during initiation or titration of tolvaptan. Overall, in this trial, subjects will undergo treatment with tolvaptan or placebo for 30 (+2) days and a post-last dose follow-up phase of 14 days.


Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Current Primary Outcome: Change in serum sodium concentration [ Time Frame: Daily up to day 4 ]

The average daily area under the curve (AUC) of change from baseline in serum sodium level up to Day 4 within the double-blind treatment period.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change of average daily AUC from baseline at each visit in serum sodium level. [ Time Frame: Daily up to Day 30 ]
  • Change from baseline in serum sodium concentration at Day 4. [ Time Frame: Day 4 ]
  • Change from baseline in serum sodium concentration at Day 30. [ Time Frame: Daily up to Day 30 ]
  • Percentage of subjects who require rescue therapy or fluid restriction at any time during the double-blind treatment period. [ Time Frame: Daily up to Day 30 ]
  • Changes from baseline in ALT, AST and Total Bilirubin [ Time Frame: Daily up to Day 30 ]
  • Clinically significant changes in vital signs. [ Time Frame: Daily up to Day 30 ]
  • Incidence of dehydration AEs. [ Time Frame: Daily up to Day 30 ]
  • Tanner staging progression score (at 30 days) [ Time Frame: Daily up to Day 30 ]
  • Percentage of subjects with overly rapid correction in serum sodium ( ≥ 12 mmol/L in 24 hours). [ Time Frame: Daily up to Day 30 ]


Original Secondary Outcome:

  • Change of average daily AUC from baseline at each visit in serum sodium level. [ Time Frame: Daily up to Day 30 ]
  • Change from baseline in serum sodium concentration at Day 4. [ Time Frame: Day 4 ]
  • Change from baseline in serum sodium concentration at Day 30. [ Time Frame: Daily up to Day 30 ]
  • Percentage of subjects who require rescue therapy or fluid restriction at any time during the double-blind treatment period. [ Time Frame: Daily up to Day 30 ]
  • Abnormal liver function test changes from baseline. [ Time Frame: Daily up to Day 30 ]
  • Clinically significant changes in vital signs. [ Time Frame: Daily up to Day 30 ]
  • Incidence of dehydration AEs. [ Time Frame: Daily up to Day 30 ]
  • Abnormal changes in Tanner stage from baseline to Day 30. [ Time Frame: Daily up to Day 30 ]
  • Percentage of subjects with overly rapid correction in serum sodium ( ≥ 12 mmol/L in 24 hours). [ Time Frame: Daily up to Day 30 ]


Information By: Otsuka Pharmaceutical Development & Commercialization, Inc.

Dates:
Date Received: May 8, 2015
Date Started: November 2015
Date Completion: August 2017
Last Updated: March 27, 2017
Last Verified: March 2017