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

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

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.

Study Overview

• Status: Unknown
• Conditions: Non-hypovolemic Non-acute Hyponatremia
• Intervention / Treatment: Drug: Tolvaptan; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Fusheng Wang, PhD; Email: fswang@public.bta.net.cn
• Study Contact Backup: Name: Lin Zhu; Phone Number: 051885475957; Email: acetone_zhulin@yahoo.com.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Cardiology, Beijing An Zhen Hospital Affiliated to Capital University of Medical Science
    • Contact: Suo; Phone Number: 010-64456464
    • Principal Investigator: Changsheng Ma, PhD
  • Beijing, China
    • Recruiting
    • Endocrinology, Beijing Friendship Hospital
    • Contact: Liu; Phone Number: 010-84205645
    • Principal Investigator: Wenying Yang, PhD
  • Beijing, China
    • Recruiting
    • Hepatology, No. 302 Hospital
    • Contact: Yu; Phone Number: 010-63879892
    • Principal Investigator: Fusheng Wang, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (for CHF):

1. Patients with CHF who exhibit edema, jugular venous distention, hepatomegaly, or pulmonary congestion.
2. Non-hypovolemic and Non-acute hyponatremia with a serum sodium < 135mEq/L before randomization.
3. 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.
4. Patients whose body weight has been stable (±1.0 kg) for 2 days prior to commencement of study drug administration.
5. Age:18～80 (when informed consent is obtained)，male or female.
6. In-patient subjects.
7. Informed consent.

Inclusion Criteria (for hepatic cirrhosis):

1. Patients with hepatic edema.
2. Non-hypovolemic and non acute hyponatremia with a serum sodium < 135mEq/L before randomization.
3. Age:18～65 (when informed consent is obtained)，male or female.
4. In-patient subjects.
5. Informed consent.

Inclusion Criteria (for SIADH and others):

1. Patients with SIADH arising from a variety of etiologies.
2. Non-hypovolemic and non acute hyponatremia with a serum sodium < 135mEq/L before randomization.
3. Age:18～80 (when informed consent is obtained)，male or female.
4. In-patient subjects.
5. Informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug: Tolvaptan	Drug: Tolvaptan; 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.
Placebo Comparator: Drug: Placebo	Drug: Placebo; placebo plus conventional therapy according to each patient's underlying disease, such as CHF, hepatic cirrhosis and SIADH or others.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborators: Beijing Friendship Hospital; Beijing 302 Hospital; Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Anticipated): September 1, 2012
• Study Completion (Anticipated): September 1, 2012

Study Registration Dates

• First Submitted: January 5, 2012
• First Submitted That Met QC Criteria: January 8, 2012
• First Posted (Estimate): January 11, 2012

Study Record Updates

• Last Update Posted (Estimate): January 11, 2012
• Last Update Submitted That Met QC Criteria: January 8, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: hyponatremia; Tolvaptan; Non-hypovolemic and Non-acute hyponatremia
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyponatremia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: HENGRUI20111231