Syndrome of Inappropriate Antidiuretic Hormone Secretion
Conditions
Brief summary
The objective of this study is to investigate the efficacy and safety of tolvaptan based on the change in serum sodium concentration following administration of tolvaptan oral tablets at 7.5 to 60 mg/day for up to 30 days in patients with hyponatremia in the SIADH.
Interventions
Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with a definite diagnosis of SIADH in reference to Diagnostic and Treatment Manual of the Hypersecretion of Vasopressin (SIADH), Revised in 2011 * Subjects who have been on fluid restriction for at least 7 consecutive days at the time of informed consent and who are showing no improvement of hyponatremia at the time of the screening examination
Exclusion criteria
* Subjects who have transient hyponatremia induced by drug administration * Subjects who are unable to sense thirst or who have difficulty with fluid intake * Subjects with urinary tract obstruction * Subjects who have participated in any other clinical trial within 30 days prior to informed consent * Subjects with serum sodium concentration of \<120 mEq/L associated with neurologic impairment, including apathy, confusion, or seizures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration | Baseline, Day2, Day3, Day4, Day5, Day7, Day14, Day21, Day after final study medication | The percentage of subjects with normalized serum sodium concentration, defined as ≥135 mEq/L, on the day after final IMP administration will be calculated versus the number of subjects with serum sodium concentration of \<135 mEq/L at baseline on Day 1 of the treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Sodium Concentration | Day2, Day3, Day4, Day5, Day7, Day14, Day21 and the day after final IMP administration | The mean and standard error of measured values for serum sodium concentration on the day of fixing the maintenance dose and on the day after final IMP administration were calculated. The day of fixing the maintenance dose: Day2, Day3, Day4, Day5, Day7, Day14, and Day21 |
Countries
Japan
Participant flow
Recruitment details
This trial was conducted in 16 participants from 31 trial sites in Japan.
Pre-assignment details
Adults with a definite diagnosis of SIADH in reference to Diagnostic and Treatment Manual of the Hypersecretion of Vasopressin (SIADH), Revised in 2011
Participants by arm
| Arm | Count |
|---|---|
| Tolvaptan Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days.
Tolvaptan Oral Tablet: Tolvaptan tablets at 7.5, 15, 30 (one tablet each), or 60 mg (two 30 mg tablets) will be orally administered once daily after breakfast for up to 30 days. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Participant Met Withdrawal Criteria | 2 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Tolvaptan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 71.9 years STANDARD_DEVIATION 6.1 |
| Race/Ethnicity, Customized Japanese | 16 Participants |
| Region of Enrollment Japan | 16 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 16 |
| other Total, other adverse events | 15 / 16 |
| serious Total, serious adverse events | 5 / 16 |
Outcome results
Primary
Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration
The percentage of subjects with normalized serum sodium concentration, defined as ≥135 mEq/L, on the day after final IMP administration will be calculated versus the number of subjects with serum sodium concentration of \<135 mEq/L at baseline on Day 1 of the treatment period.
Time frame: Baseline, Day2, Day3, Day4, Day5, Day7, Day14, Day21, Day after final study medication
Population: Efficacy sample consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline efficacy evaluation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tolvaptan | Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration | Day2 | 43.8 percentage of participants |
| Tolvaptan | Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration | Day3 | 80 percentage of participants |
| Tolvaptan | Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration | Day4 | 80 percentage of participants |
| Tolvaptan | Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration | Day5 | 85.7 percentage of participants |
| Tolvaptan | Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration | Day7 | 92.9 percentage of participants |
| Tolvaptan | Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration | Day14 | 83.3 percentage of participants |
| Tolvaptan | Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration | Day21 | 81.8 percentage of participants |
| Tolvaptan | Percentage of Subjects With Normalized Serum Sodium Concentration on the Day After Final IMP Administration | Day after final study medication | 81.3 percentage of participants |
Secondary
Change in Serum Sodium Concentration
The mean and standard error of measured values for serum sodium concentration on the day of fixing the maintenance dose and on the day after final IMP administration were calculated. The day of fixing the maintenance dose: Day2, Day3, Day4, Day5, Day7, Day14, and Day21
Time frame: Day2, Day3, Day4, Day5, Day7, Day14, Day21 and the day after final IMP administration
Population: Efficacy sample consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline efficacy evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolvaptan | Change in Serum Sodium Concentration | Day after final study medication | 11.0 mEq/L | Standard Error 4.3 |
| Tolvaptan | Change in Serum Sodium Concentration | Day2 | 6.9 mEq/L | Standard Error 2.6 |
| Tolvaptan | Change in Serum Sodium Concentration | Day3 | 8.1 mEq/L | Standard Error 3.8 |
| Tolvaptan | Change in Serum Sodium Concentration | Day4 | 8.5 mEq/L | Standard Error 4.6 |
| Tolvaptan | Change in Serum Sodium Concentration | Day5 | 8.8 mEq/L | Standard Error 4.4 |
| Tolvaptan | Change in Serum Sodium Concentration | Day7 | 10.0 mEq/L | Standard Error 4.5 |
| Tolvaptan | Change in Serum Sodium Concentration | Day14 | 10.8 mEq/L | Standard Error 3.7 |
| Tolvaptan | Change in Serum Sodium Concentration | Day21 | 10.4 mEq/L | Standard Error 6 |