Clinical Trial: An Extension Follow-up Trial to Evaluate the Long-term Safety of Children and Adolescent Subjects With Euvolemic or Hypervolemic Hyponatremia

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

Official Title: A Phase 3b, Multicenter, Extension Follow-up Trial to Evaluate the Long-term Safety of Children and Adolescent Subjects With Euvolemic or Hypervolemic Hyponatremia Who Hav

Brief Summary: The objective of this trial is to provide 6 months of safety follow-up for children and adolescents with dilutional (euvolemic or hypervolemic) hyponatremia who have previously participated in a tolvaptan hyponatremia trial, and to assess the efficacy of tolvaptan in increasing serum sodium for those subjects who receive optional continuing tolvaptan treatment of variable duration (up to 6 months).

Detailed Summary:

Core Safety Follow-up Component • For all subjects: To evaluate the post-treatment safety follow-up of children and adolescent subjects with dilutional (euvolemic or hypervolemic) hyponatremia who have previously participated in a tolvaptan hyponatremia trial.

Optional Tolvaptan Treatment Component

• For subjects who receive optional tolvaptan treatment: To demonstrate that tolvaptan safely and effectively achieves and maintains increased serum sodium concentrations in children and adolescent subjects with dilutional (euvolemic or hypervolemic) hyponatremia when used for both multiple short-term treatments, and/or longer chronic treatments.


Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Current Primary Outcome: Change from baseline in serum sodium while tolvaptan is being administered [ Time Frame: Up to 6 months ]

Original Primary Outcome:

  • Adverse Events, including cases of dehydration. [ Time Frame: Minimum 6 months ]
    Percent of Patients reporting Adverse Events.
  • Vital signs of potential clinical relevance - Mean change from baseline to study completion. [ Time Frame: Minimum 6 months ]
    Vital Signs of Potential Clinical Relevance - Mean Change from Baseline to study completion.
  • Body weight of potential clinical relevance - Mean change from baseline to study completion. [ Time Frame: Minimum 6 months ]
    Body weight of potential clinical relevance - Mean change from baseline to study completion.
  • Height of potential clinical relevance - Mean change from baseline to study completion. [ Time Frame: Minimum 6 months ]
    Height of potential clinical relevance - Mean change from baseline to study completion.
  • Growth percentiles of potential clinical relevance - Mean change from baseline to study completion. [ Time Frame: Minimum 6 months ]
    Growth percentiles of potential clinical relevance - Mean change from baseline to study completion.
  • Tanner stages of potential clinical relevance - Mean change from baseline to study completion. [ Time Frame: Minimum 6 months ]
    Tanner stages of potential clinical relevance - Mean change from baseline to study completion.


Current Secondary Outcome:

  • Percentage of subjects who require rescue therapy while on tolvaptan treatment [ Time Frame: Up to 6 months ]
  • Percentage of subjects who have recurrence of hyponatremia while on tolvaptan [ Time Frame: Up to 6 months ]
  • Percentage of subjects requiring continuation of tolvaptan following 30 days of treatment [ Time Frame: Up to 6 months ]
  • Change from baseline in QoL assessments (monthly for subjects on tolvaptan [ Time Frame: Up to 6 months ]
  • Percentage of subjects with overly rapid correction in serum sodium(≥ 12 mEq/L [mmol/L]) in 24 hours after the first dose at introduction or reintroduction of tolvaptan [ Time Frame: Up to 6 months ]
  • Changes from baseline in ALT, AST, BT, and creatinine for subjects on tolvaptan [ Time Frame: Up to 6 months ]
  • Frequency of AE reports (including cases of dehydration) [ Time Frame: Up to 6 months ]
  • Changes from baseline in growth percentiles by visit for body height and weight [ Time Frame: Up to 6 months ]
  • Tanner Staging progression score [ Time Frame: Up to 6 months ]
  • Plasma concentrations of tolvaptan and metabolites in subjects who have continued tolvaptan therapy for 8 consecutive weeks [ Time Frame: Greater than or equal to 8 weeks ]


Original Secondary Outcome:

  • Change in serum sodium from baseline at each visit while IMP is being administered. [ Time Frame: Minimum 6 months ]
  • Plasma concentrations of tolvaptan and metabolites in subjects who have continued tolvaptan therapy for 8 consecutive weeks. [ Time Frame: 8 weeks. ]
    Plasma concentrations of tolvaptan and metabolites in subjects who have continued tolvaptan therapy for 8 consecutive weeks.


Information By: Otsuka Pharmaceutical Development & Commercialization, Inc.

Dates:
Date Received: December 18, 2013
Date Started: April 2016
Date Completion: May 2020
Last Updated: April 24, 2017
Last Verified: April 2017