Trial Outcomes & Findings for An Extension Follow-up Trial to Evaluate the Long-term Safety of Children and Adolescent Participants With Euvolemic or Hypervolemic Hyponatremia (NCT NCT02020278)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

3 participants

Primary outcome timeframe

Baseline, Month 6

Results posted on

2020-04-17

Participant Flow

Eligible participants included those enrolled in a previous tolvaptan pediatric trial for hyponatremia (NCT02012959); who provided written informed consent at baseline and were able to understand that he/she could withdraw at any time; with the ability to comply with all requirements of the trial; ready to be followed up for 6 months.

There was no screening phase. Approximately 100 male or female participants were planned to be enrolled in this trial. A total of 3 participants were enrolled in this trial, but no participant received optional investigational medicinal product during this trial.

Participant milestones

Participant milestones
Measure	Tolvaptan All participants enrolled first entered a 6-month follow-up trial that evaluated post-treatment safety after participation in a tolvaptan hyponatremia trial. Participants were then eligible to receive open-label tolvaptan if they had a clinical need as determined by the investigator and met the eligibility criteria for optional tolvaptan treatment during the 6-month follow-up period. In this trial, no participants qualified for treatment during the 6-month follow-up period. Daily dose levels would have included 3.75 milligrams (mg), 7.5 mg, 15 mg, 30 mg, and 60 mg.
Core Safety Follow-up Component STARTED	3
Core Safety Follow-up Component COMPLETED	3
Core Safety Follow-up Component NOT COMPLETED	0
Optional Tolvaptan Treatment Component STARTED	0
Optional Tolvaptan Treatment Component COMPLETED	0
Optional Tolvaptan Treatment Component NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline data not reported

PRIMARY outcome

Timeframe: Baseline, Month 6

Population: No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 6

Population: No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 6

Population: No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 6

Population: No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All enrolled participants with analyzable data at specified timepoint. No enrolled participant received any investigational medicinal product during the study.

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.

Outcome measures

Outcome measures
Measure	Optional Tolvaptan Treatment Component n=1 Participants The duration for the optional tolvaptan treatment (referred to as optional tolvaptan treatment component) was to be case-specific. It could have been short-term or long-term and could have consisted of 1 or more treatment cycles. Eligibility for optional tolvaptan treatment was to be determined at the pretreatment baseline visit of each dosing cycle. Each tolvaptan treatment cycle was to include a titration phase of up to 4 days and interruption of tolvaptan for up to 2 doses after 30 (±1) days of tolvaptan treatment. Due to early study termination, no participant entered the Optional Tolvaptan Treatment Component of this study.
Change From Baseline In Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale (GCS) Total Score At Month 6	-3.5 units on a scale Interval -3.5 to -3.5

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All enrolled participants with analyzable data at specified timepoint. No enrolled participant received any investigational medicinal product during the study.

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.

Outcome measures

Outcome measures
Measure	Optional Tolvaptan Treatment Component n=1 Participants The duration for the optional tolvaptan treatment (referred to as optional tolvaptan treatment component) was to be case-specific. It could have been short-term or long-term and could have consisted of 1 or more treatment cycles. Eligibility for optional tolvaptan treatment was to be determined at the pretreatment baseline visit of each dosing cycle. Each tolvaptan treatment cycle was to include a titration phase of up to 4 days and interruption of tolvaptan for up to 2 doses after 30 (±1) days of tolvaptan treatment. Due to early study termination, no participant entered the Optional Tolvaptan Treatment Component of this study.
Change From Baseline In PedsQL GCS Physical Health Summary Score At Month 6	12.5 units on a scale Interval 12.5 to 12.5

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All enrolled participants with analyzable data at specified timepoint. No enrolled participant received any investigational medicinal product during the study.

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.

Outcome measures

Outcome measures
Measure	Optional Tolvaptan Treatment Component n=1 Participants The duration for the optional tolvaptan treatment (referred to as optional tolvaptan treatment component) was to be case-specific. It could have been short-term or long-term and could have consisted of 1 or more treatment cycles. Eligibility for optional tolvaptan treatment was to be determined at the pretreatment baseline visit of each dosing cycle. Each tolvaptan treatment cycle was to include a titration phase of up to 4 days and interruption of tolvaptan for up to 2 doses after 30 (±1) days of tolvaptan treatment. Due to early study termination, no participant entered the Optional Tolvaptan Treatment Component of this study.
Change From Baseline In PedsQL GCS Psychosocial Health Summary Score At Month 6	-13.5 units on a scale Interval -13.5 to -13.5

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All enrolled participants with analyzable data at specified timepoint. No enrolled participant received any investigational medicinal product during the study.

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.

Outcome measures

Outcome measures
Measure	Optional Tolvaptan Treatment Component n=1 Participants The duration for the optional tolvaptan treatment (referred to as optional tolvaptan treatment component) was to be case-specific. It could have been short-term or long-term and could have consisted of 1 or more treatment cycles. Eligibility for optional tolvaptan treatment was to be determined at the pretreatment baseline visit of each dosing cycle. Each tolvaptan treatment cycle was to include a titration phase of up to 4 days and interruption of tolvaptan for up to 2 doses after 30 (±1) days of tolvaptan treatment. Due to early study termination, no participant entered the Optional Tolvaptan Treatment Component of this study.
Change From Baseline In PedsQL Multidimensional Fatigue Scale (MFS) Total Score At Month 6	9.7 units on a scale Interval 9.7 to 9.7

SECONDARY outcome

Timeframe: Month 6

Population: No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 Weeks

Population: No enrolled participant received any investigational medicinal product during the study. Due to early study termination, no pharmacokinetic analyses were performed.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 6

Population: All enrolled participants with analyzable data at specified timepoint. No enrolled participant received any investigational medicinal product during the study.

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.

Outcome measures

Outcome measures
Measure	Optional Tolvaptan Treatment Component n=3 Participants The duration for the optional tolvaptan treatment (referred to as optional tolvaptan treatment component) was to be case-specific. It could have been short-term or long-term and could have consisted of 1 or more treatment cycles. Eligibility for optional tolvaptan treatment was to be determined at the pretreatment baseline visit of each dosing cycle. Each tolvaptan treatment cycle was to include a titration phase of up to 4 days and interruption of tolvaptan for up to 2 doses after 30 (±1) days of tolvaptan treatment. Due to early study termination, no participant entered the Optional Tolvaptan Treatment Component of this study.
Participants With A Tanner Staging Score Of 1 At Month 6	2 Participants

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All enrolled participants with analyzable data at specified timepoint. No enrolled participant received any investigational medicinal product during the study.

Changes from baseline in growth percentiles for body height and weight were calculated and are reported.

Outcome measures

Outcome measures
Measure	Optional Tolvaptan Treatment Component n=3 Participants The duration for the optional tolvaptan treatment (referred to as optional tolvaptan treatment component) was to be case-specific. It could have been short-term or long-term and could have consisted of 1 or more treatment cycles. Eligibility for optional tolvaptan treatment was to be determined at the pretreatment baseline visit of each dosing cycle. Each tolvaptan treatment cycle was to include a titration phase of up to 4 days and interruption of tolvaptan for up to 2 doses after 30 (±1) days of tolvaptan treatment. Due to early study termination, no participant entered the Optional Tolvaptan Treatment Component of this study.
Change From Baseline In Growth Percentiles For Body Height And Weight At Month 6 Height Percentile	19.0 percentile Standard Deviation 40.0
Change From Baseline In Growth Percentiles For Body Height And Weight At Month 6 Weight Percentile	0.7 percentile Standard Deviation 8.0

SECONDARY outcome

Timeframe: Baseline, Month 2

Population: All enrolled participants with analyzable data at specified timepoint. No enrolled participant received any investigational medicinal product during the study. Due to early study termination, efficacy data were not collected.

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).

Outcome measures

Outcome measures
Measure	Optional Tolvaptan Treatment Component n=2 Participants The duration for the optional tolvaptan treatment (referred to as optional tolvaptan treatment component) was to be case-specific. It could have been short-term or long-term and could have consisted of 1 or more treatment cycles. Eligibility for optional tolvaptan treatment was to be determined at the pretreatment baseline visit of each dosing cycle. Each tolvaptan treatment cycle was to include a titration phase of up to 4 days and interruption of tolvaptan for up to 2 doses after 30 (±1) days of tolvaptan treatment. Due to early study termination, no participant entered the Optional Tolvaptan Treatment Component of this study.
Change From Baseline In Alanine Aminotransferase (ALT) And Aspartate Aminotransferase (AST) For Participants On Tolvaptan At Month 2 ALT	-10.00 U/L Standard Deviation 45.25
Change From Baseline In Alanine Aminotransferase (ALT) And Aspartate Aminotransferase (AST) For Participants On Tolvaptan At Month 2 AST	-7.50 U/L Standard Deviation 0.71

SECONDARY outcome

Timeframe: Baseline, Month 2

Population: All enrolled participants with analyzable data at specified timepoint. No enrolled participant received any investigational medicinal product during the study.

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.

Outcome measures

Outcome measures
Measure	Optional Tolvaptan Treatment Component n=2 Participants The duration for the optional tolvaptan treatment (referred to as optional tolvaptan treatment component) was to be case-specific. It could have been short-term or long-term and could have consisted of 1 or more treatment cycles. Eligibility for optional tolvaptan treatment was to be determined at the pretreatment baseline visit of each dosing cycle. Each tolvaptan treatment cycle was to include a titration phase of up to 4 days and interruption of tolvaptan for up to 2 doses after 30 (±1) days of tolvaptan treatment. Due to early study termination, no participant entered the Optional Tolvaptan Treatment Component of this study.
Change From Baseline In Bilirubin For Participants On Tolvaptan At Month 2	2.57 umol/L Standard Deviation 3.63

Adverse Events

Tolvaptan

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tolvaptan n=3 participants at risk All participants enrolled first entered a 6-month follow-up trial that evaluated post-treatment safety after participation in a tolvaptan hyponatremia trial. Participants were then eligible to receive open-label tolvaptan if they had a clinical need as determined by the investigator and met the eligibility criteria for optional tolvaptan treatment during the 6-month follow-up period. In this trial, no participants qualified for treatment during the 6-month follow-up period. Daily dose levels would have included 3.75 milligrams (mg), 7.5 mg, 15 mg, 30 mg, and 60 mg.
General disorders Pyrexia	33.3% 1/3 • Baseline to Month 6
Infections and infestations Enterovirus Infection	33.3% 1/3 • Baseline to Month 6
Infections and infestations Rhinovirus Infection	33.3% 1/3 • Baseline to Month 6
Infections and infestations Urosepsis	33.3% 1/3 • Baseline to Month 6

Other adverse events

Other adverse events
Measure	Tolvaptan n=3 participants at risk All participants enrolled first entered a 6-month follow-up trial that evaluated post-treatment safety after participation in a tolvaptan hyponatremia trial. Participants were then eligible to receive open-label tolvaptan if they had a clinical need as determined by the investigator and met the eligibility criteria for optional tolvaptan treatment during the 6-month follow-up period. In this trial, no participants qualified for treatment during the 6-month follow-up period. Daily dose levels would have included 3.75 milligrams (mg), 7.5 mg, 15 mg, 30 mg, and 60 mg.
General disorders Pyrexia	33.3% 1/3 • Baseline to Month 6
Infections and infestations Bronchitis	33.3% 1/3 • Baseline to Month 6
Infections and infestations Enterovirus Infection	33.3% 1/3 • Baseline to Month 6
Infections and infestations Rhinovirus Infection	33.3% 1/3 • Baseline to Month 6
Infections and infestations Urosepsis	33.3% 1/3 • Baseline to Month 6
Infections and infestations Viral Upper Respiratory Tract Infection	33.3% 1/3 • Baseline to Month 6

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 1-609-524-6788

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
Publication restrictions are in place

Restriction type: OTHER