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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-hypovolemic Non-acute Hyponatremia	Drug: Tolvaptan; Drug: Placebo	Phase 2; Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	240 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	January 2012
Estimated Primary Completion Date :	September 2012
Estimated Study Completion Date :	September 2012

Arms and Interventions

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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.

Outcome Measures

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Primary Outcome Measures :

1. 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 [ Time Frame: 4 and 7 days ]

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Contacts

Contact: Fusheng Wang, PhD		fswang@public.bta.net.cn
Contact: Lin Zhu	051885475957	acetone_zhulin@yahoo.com.cn

Locations

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

Sponsors and Collaborators

Jiangsu HengRui Medicine Co., Ltd.

Beijing 302 Hospital

Beijing Anzhen Hospital

Beijing Friendship Hospital

More Information

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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier:	NCT01507727 History of Changes
Other Study ID Numbers:	HENGRUI20111231
First Posted:	January 11, 2012
Last Update Posted:	January 11, 2012
Last Verified:	January 2012

Keywords provided by Jiangsu HengRui Medicine Co., Ltd.:

hyponatremia; Non-hypovolemic and Non-acute hyponatremia; Tolvaptan

Additional relevant MeSH terms:

Hyponatremia; Water-Electrolyte Imbalance; Metabolic Diseases; Tolvaptan	Antidiuretic Hormone Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Physiological Effects of Drugs