A Multicenter Trial to Investigate the Efficacy and Safety of Tolvaptan in Patients With Hyponatremia in SIADH

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Uncontrolled, Open-label, Dose-titration Trial to Investigate the Efficacy and Safety of Tolvaptan Tablets in Patients With Hyponatremia in Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Conditions
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Syndrome of Inappropriate Antidiuretic Hormone Secretion

Intervention / Treatment
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* Drug: Tolvaptan Oral Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tolvaptan<br>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. | Drug: Tolvaptan Oral Tablet<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Day2, Day3, Day4, Day5, Day7, Day14, Day21, Day after final study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Day2, Day3, Day4, Day5, Day7, Day14, Day21 and the day after final IMP administration |