Efficacy and Safety Study of the Tolvaptan Tablets in Patients With Non-hypovolemic Non-acute Hyponatremia

Study Overview
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Brief Summary
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This drug has been developed to treat Hyponatremia. The primary purpose of this study is to verify the efficacy and safety of seven-day repeated oral administration of tolvaptan at 15, 30, and 60 mg or placebo in patients with Non-hypovolemic Non-acute Hyponatremia secondary to Congestive Heart Failure (CHF), hepatic cirrhosis or Syndrome of Inappropriate Antidiuretic Hormone (SIADH), despite receiving standard therapy. This study is being conducted in China.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled (Standard Therapy + Placebo) Study to Evaluate the Efficacy and Safety of the Tolvaptan Tablets in Patients With Non-hypovolemic Non-acute Hyponatremia

Conditions
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Non-hypovolemic Non-acute Hyponatremia

Intervention / Treatment
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* Drug: Tolvaptan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (for CHF): Patients with CHF who exhibit edema, jugular venous distention, hepatomegaly, or pulmonary congestion. Non-hypovolemic and Non-acute hyponatremia with a serum sodium < 135mEq/L before randomization. Patients who have taken furosemide at 40 mg/d or more (oral dosing) without alteration of dosage for the 3 days of the observation period. Patients whose body weight has been stable (±1.0 kg) for 2 days prior to commencement of study drug administration. Age:18～80 (when informed consent is obtained)，male or female. In-patient subjects. Informed consent. Inclusion Criteria (for hepatic cirrhosis): Patients with hepatic edema. Non-hypovolemic and non acute hyponatremia with a serum sodium < 135mEq/L before randomization. Age:18～65 (when informed consent is obtained)，male or female. In-patient subjects. Informed consent. Inclusion Criteria (for SIADH and others): Patients with SIADH arising from a variety of etiologies. Non-hypovolemic and non acute hyponatremia with a serum sodium < 135mEq/L before randomization. Age:18～80 (when informed consent is obtained)，male or female. In-patient subjects. Informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: Tolvaptan<br> | Drug: Tolvaptan<br>* Tablet;15mg/tab; 30mg/tab; 15/30/60mg/day for 7 days Plus conventional therapy according to each patient's underlying disease, such as CHF, hepatic cirrhosis and SIADH or others.<br>|
| Placebo Comparator: Drug: Placebo<br> | Drug: Placebo<br>* placebo plus conventional therapy according to each patient's underlying disease, such as CHF, hepatic cirrhosis and SIADH or others.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of average daily Area Under the Curve (AUC) of serum sodium by day 4 and 7 comparing with baseline serum sodium level within the double-blind therapy period |  | 4 and 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with normalized serum sodium at Day 4 |  | 4 day | 
| Percentage of patients with normalized serum sodium at Day 7 |  | 7 day | 
| Time to first normalization in serum sodium |  | up to 7 days | 
| Change from baseline in serum sodium at Day 4 |  | 4 day | 
| Change from baseline in serum sodium at Day 7 |  | 7 day | 
| Percentage of patients requiring fluid restriction at any time during the double-blind therapy period of the study |  | up to 7 days | 
| 24-hour urine output |  | day 1, day 2, day 3, day 4, day 5, day 6 and day 7 | 
| Change from baseline in body weight (hypervolemic patients only) |  | day 1, day 2, day 3, day 4, day 5, day 6 and day 7 | 
| Fluid balance (hypervolemic patients only) |  | day 1, day 2, day 3, day 4, day 5, day 6 and day 7 | 
| The percentage of patients who are designated as treatment failure due to the need for saline infusion, with or without fluid restriction |  | up to 7 days | 
| For CHF patients, improvement of symptoms and relevant physical examination measures |  | day 1, day 2, day 3, day 4, day 5, day 6 and day 7 | 
| For hepatic edema patients, improvement of symptoms and relevant physical examination measures or ultrasound test findings |  | day 1, day 2, day 3, day 4, day 5, day 6 and day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyponatremia, Non-hypovolemic and Non-acute hyponatremia, Tolvaptan