The objective of this trial was to provide 6 months of safety follow-up for children and adolescents with dilutional (euvolemic or hypervolemic) hyponatremia who had previously participated in a tolvaptan hyponatremia trial and to assess the efficacy of tolvaptan in increasing serum sodium for those participants who received optional continuing tolvaptan treatment of variable duration (up to 6 months).
Core Safety Follow-up Component • For all participants: To evaluate the post-treatment safety follow-up of children and adolescent participants with dilutional (euvolemic or hypervolemic) hyponatremia who have previously participated in a tolvaptan hyponatremia trial. Optional Tolvaptan Treatment Component • For participants who receive optional tolvaptan treatment: To demonstrate that tolvaptan safely and effectively achieves and maintains increased serum sodium concentrations in children and adolescent participants with dilutional (euvolemic or hypervolemic) hyponatremia when used for both multiple short-term treatments, and/or longer chronic treatments.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Tolvaptan 3.75-, 7.5-, 15-, and 30-mg spray-dried tablets. Dosage: Depending on age and weight, Tablet (3.75 mg - 60 mg daily). Frequency: Once daily. Duration: Participants may be eligible to receive short-term or long-term optional tolvaptan treatment at any time during their participation in the trial, with one or more treatment cycles over a 6-month period.
Unnamed facility
Aurora, Colorado, United States
Unnamed facility
Washington D.C., District of Columbia, United States
Change From Baseline At Month 6 In Serum Sodium While Tolvaptan Was Being Administered
No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected for this outcome measure.
Time frame: Baseline, Month 6
Percentage Of Participants Who Required Rescue Therapy While On Tolvaptan Treatment
No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected for this outcome measure.
Time frame: Month 6
Percentage Of Participants Who Had Recurrence Of Hyponatremia While On Tolvaptan
No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected for this outcome measure.
Time frame: Month 6
Percentage Of Participants Requiring Continuation Of Tolvaptan Following 30 Days Of Treatment
No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected for this outcome measure.
Time frame: Month 6
Change From Baseline In Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale (GCS) Total Score At Month 6
The PedsQL GCS was used for quality of life assessment. It is appropriate for at least 2 years of age, however availability may be limited for certain ages and languages. It encompasses 4 dimensions of functioning (physical, emotional, social, school). The age groups covered are: Toddler (2-4 years), Young child (5-7 years), Child (8-12 years), and Adolescent (13-18 years). Depending on the participant's age, the questionnaire may be completed by either the participant or the parent/caregiver, as appropriate. For the Toddler group, the PedsQL GCS consists of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL GCS consists of 23 items, with a 3-point Likert scale (0, 2, 4) for the Young Child, and a 5-point Likert scale for the Child and Adolescent groups. Scores are transformed on a scale from 0 to 100 and averaged. Higher scores indicate improved quality of life. The change from baseline in the GCS total score is presented.
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Unnamed facility
Atlanta, Georgia, United States
Unnamed facility
Grand Rapids, Michigan, United States
Unnamed facility
Kansas City, Missouri, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Stony Brook, New York, United States
Unnamed facility
The Bronx, New York, United States
Unnamed facility
Cleveland, Ohio, United States
Unnamed facility
Philadelphia, Pennsylvania, United States
...and 13 more locations
Time frame: Baseline, Month 6
Change From Baseline In PedsQL GCS Physical Health Summary Score At Month 6
The PedsQL GCS was used for quality of life assessment. It is appropriate for at least 2 years of age, however availability may be limited for certain ages and languages. It encompasses 4 dimensions of functioning (physical, emotional, social, school). The age groups covered are: Toddler (2-4 years), Young child (5-7 years), Child (8-12 years), and Adolescent (13-18 years). Depending on the participant's age, the questionnaire may be completed by either the participant or the parent/caregiver, as appropriate. For the Toddler group, the PedsQL GCS consists of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL GCS consists of 23 items, with a 3-point Likert scale (0, 2, 4) for the Young Child, and a 5-point Likert scale for the Child and Adolescent groups. Scores are transformed on a scale from 0 to 100 and averaged. Higher scores indicate improved quality of life. The change from baseline in the physical health dimension is presented.
Time frame: Baseline, Month 6
Change From Baseline In PedsQL GCS Psychosocial Health Summary Score At Month 6
The PedsQL GCS was used for quality of life assessment. It is appropriate for at least 2 years of age, however availability may be limited for certain ages and languages. It encompasses 4 dimensions of functioning (physical, emotional, social, school). The age groups covered are: Toddler (2-4 years), Young child (5-7 years), Child (8-12 years), and Adolescent (13-18 years). Depending on the participant's age, the questionnaire may be completed by either the participant or the parent/caregiver, as appropriate. For the Toddler group, the PedsQL GCS consists of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL GCS consists of 23 items, with a 3-point Likert scale (0, 2, 4) for the Young Child, and a 5-point Likert scale for the Child and Adolescent groups. Scores are transformed on a scale from 0 to 100 and averaged. Higher scores indicate improved quality of life. The change from baseline in summed emotional, social, and school dimensions is presented.
Time frame: Baseline, Month 6
Change From Baseline In PedsQL Multidimensional Fatigue Scale (MFS) Total Score At Month 6
The PedsQL GCS was used for quality of life assessment. It is appropriate for at least 2 years of age, however availability may be limited for certain ages and languages. It encompasses 4 dimensions of functioning (physical, emotional, social, school). The age groups covered are: Toddler (2-4 years), Young child (5-7 years), Child (8-12 years), and Adolescent (13-18 years). Depending on the participant's age, the questionnaire may be completed by either the participant or the parent/caregiver, as appropriate. For the Toddler group, the PedsQL GCS consists of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL GCS consists of 23 items, with a 3-point Likert scale (0, 2, 4) for the Young Child, and a 5-point Likert scale for the Child and Adolescent groups. Scores are transformed on a scale from 0 to 100 and averaged. Higher scores indicate improved quality of life. The change from baseline in summed emotional, social, and school dimensions is presented.
Time frame: Baseline, Month 6
Percentage Of Participants With Overly Rapid Correction In Serum Sodium 24 Hours After The First Dose At Introduction Or Reintroduction Of Tolvaptan
No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected for this outcome measure.
Time frame: Month 6
Plasma Concentrations Of Tolvaptan And Metabolites In Participants Who Had Continued Tolvaptan Therapy For Eight Consecutive Weeks
No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected for this outcome measure.
Time frame: 8 Weeks
Participants With A Tanner Staging Score Of 1 At Month 6
Tanner Staging assessment consists of 2 domains (pubic hair and breast development) for girls and 3 domains (pubic hair, penis development, and testes development) for boys. Staging was based on a single score summarizing the domains (not individual domain scores). Stages range from 1-5, with 1 indicating preadolescent and 5 adult. Participants with a Tanner staging score of 1 (preadolescent) at Month 6 are reported.
Time frame: Month 6
Change From Baseline In Growth Percentiles For Body Height And Weight At Month 6
Changes from baseline in growth percentiles for body height and weight were calculated and are reported.
Time frame: Baseline, Month 6
Change From Baseline In Alanine Aminotransferase (ALT) And Aspartate Aminotransferase (AST) For Participants On Tolvaptan At Month 2
No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected. Data reported only include assessments made for ALT and AST during the Core Safety Follow-up Component of the trial. Results are reported in units/liter (U/L).
Time frame: Baseline, Month 2
Change From Baseline In Bilirubin For Participants On Tolvaptan At Month 2
No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected. Data reported only include assessments made for bilirubin during the Core Safety Follow-up Component of the trial. Results are reported in micromoles (umol)/L.
Time frame: Baseline, Month 2