Trial Outcomes & Findings for Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of Tolvaptan in Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload (NCT NCT03255226)

Last Updated: 2024-08-23

Results Overview

The primary endpoint of this trial was the percentage of subjects whose body weight on the day after the third day of treatment with tolvaptan at the evaluation dose (the third day of administration at the evaluation dose) was decreased by 1.7% or more from the weight measured before breakfast (baseline) on the first day of the treatment period (the initial tolvaptan administration day), under the condition that the mean daily urine volume for the 3 days of treatment with tolvaptan at the evaluation dose was higher than the daily urine volume for the pretreatment observation period. The percentage of subjects as well as the exact 95% confidence interval (CI) based on binomial distribution were calculated.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

60 participants

Primary outcome timeframe

Day after Day 3 at evaluation dose

Results posted on

2024-08-23

Participant Flow

Participant milestones

Participant milestones
Measure	Tolvaptan Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Overall Study STARTED	60
Overall Study COMPLETED	46
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Tolvaptan Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Overall Study Adverse Event	2
Overall Study Physician Decision	3
Overall Study Withdrawal by Subject	1
Overall Study Serum or blood sodium increased	4
Overall Study Serum or blood potassium increased	4

Baseline Characteristics

Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of Tolvaptan in Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tolvaptan n=59 Participants Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Age, Continuous	5.44 years STANDARD_DEVIATION 5.03 • n=5 Participants
Age, Customized Age group · 6 months to less than 2 years	20 Participants n=5 Participants
Age, Customized Age group · 2 years to less than 7 years	16 Participants n=5 Participants
Age, Customized Age group · 7 years to less than 15 years	23 Participants n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants
Race/Ethnicity, Customized Asian	59 Participants n=5 Participants
Region of Enrollment Japan	59 participants n=5 Participants

PRIMARY outcome

Timeframe: Day after Day 3 at evaluation dose

Outcome measures

Outcome measures
Measure	Tolvaptan n=57 Participants Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Percentages of Subjects Whose Was Decreased by 1.7% or More Body Weight From Baseline	22.8 percentage of participants Interval 12.7 to 35.8

SECONDARY outcome

Timeframe: Baseline, Day1, Day2 and Day3 of administration at evaluation dose

Population: The FAS included 59 of 60 subjects (98.3%) who received the IMP. One subject was excluded from the FAS because the subject received the IMP at least once, and discontinued the trial before the daily urine volume data on Day 1 were obtained.

Daily urine volume was measured for the time interval starting at urination (an instruction to urinate) after breakfast and ending at complete urination immediately before administration on the following day. Baseline was 100% and the change rate was calculated like this. Percent change (%) = (\[daily urine volume on the Day1, Day2 and Day3 of the tolvaptan at the evaluation dose\] - \[daily urine volume on baseline\] ) / \[daily urine volume on baseline\] ×100

Outcome measures

Outcome measures
Measure	Tolvaptan n=59 Participants Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Change Rate From Baseline in Daily Urine Volume Day 2	47.8 percentage of urine volume (mL) Standard Deviation 43.3
Change Rate From Baseline in Daily Urine Volume Day 1	53.1 percentage of urine volume (mL) Standard Deviation 52.9
Change Rate From Baseline in Daily Urine Volume Day 3	45.8 percentage of urine volume (mL) Standard Deviation 29.3

SECONDARY outcome

Timeframe: Day after Day 3 at evaluation dose

Percent change from baseline in body weight (kg) on the day after the third day of treatment with tolvaptan at the evaluation dose was evaluated. For body weight measured on the day after the third day of administration at the evaluation dose, their percent changes from baseline (before the start of tolvaptan administration on the first day of the treatment period) mean and standard deviation (SD) were calculated. Baseline was 100% and the change rate was alculated like this. Percent change (%) = (\[body weight on the day after the third day of treatment with tolvaptan at the evaluation dose\] - \[body weight on baseline\] ) / \[body weight on baseline\] ×100

Outcome measures

Outcome measures
Measure	Tolvaptan n=57 Participants Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Percent Changes From Baseline in Body Weight (kg)	-0.371 percentage of body weight (kg) Standard Deviation 2.470

SECONDARY outcome

Timeframe: Day after Day 3 at evaluation dose

The improvement rate was defined as the percentage of subjects in whom a symptom was present at baseline and then markedly improved or improved after IMP administration. Improvement category is a 4-point scale below: * Markedly improved * Improved * Unchanged * Deteriorated

Outcome measures

Outcome measures
Measure	Tolvaptan n=35 Participants Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Improvement Rates of Lower Limb Edema	68.6 percentage of participants Interval 50.7 to 83.1

SECONDARY outcome

Timeframe: Day after Day 3 at evaluation dose

Outcome measures

Outcome measures
Measure	Tolvaptan n=31 Participants Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Improvement Rates of Pulmonary Congestion	51.6 percentage of participants Interval 33.1 to 69.8

Adverse Events

Tolvaptan

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tolvaptan n=60 participants at risk Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Cardiac disorders Cardiac failure chronic	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.

Other adverse events

Other adverse events
Measure	Tolvaptan n=60 participants at risk Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Tolvaptan: Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Blood and lymphatic system disorders Anaemia	3.3% 2/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Blood and lymphatic system disorders Neutropenia	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Cardiac disorders Cardiovascular insufficiency	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Eye disorders Erythema of eyelid	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Abdominal pain	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Constipation	3.3% 2/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Dry mouth	3.3% 2/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Nausea	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Vomitng	3.3% 2/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Gastrointestinal hypomotility	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Gastrointestinal disorders Anal erythema	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
General disorders Pyrexia	3.3% 2/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
General disorders Thirst	6.7% 4/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Infections and infestations Nasopharyngitis	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Infections and infestations Urinary tract infection	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Infections and infestations Bacterial infection	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Investigations Blood pressure increased	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Investigations Blood pressure systolic decreased	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Investigations Hepatic enzyme increased	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Metabolism and nutrition disorders Dehydration	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Metabolism and nutrition disorders Hyperkalaemia	3.3% 2/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Metabolism and nutrition disorders Hypokalaemia	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Metabolism and nutrition disorders Polydipsia	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Nervous system disorders Dizziness	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Nervous system disorders Headache	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Renal and urinary disorders Renal impairment	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Skin and subcutaneous tissue disorders Pruritus	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Skin and subcutaneous tissue disorders Rash	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.
Skin and subcutaneous tissue disorders Skin exfoliation	1.7% 1/60 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days Subjects who received at least one dose of IMP were included in the safety analysis.

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., Ltd.

Phone: +81363617366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place