A Phase 2 Efficacy and Safety Study of the Tolvaptan Tablets in Patients With Non-hypovolemic Non-acute Hyponatremia

NCT ID: NCT00664014

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 241 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2010-02-28

Brief Summary

This is a randomized, double-blind, multicenter, placebo-controlled (standard therapy + placebo), phase 2 efficacy and safety study of the Tolvaptan tablets in treatment of patients with non-hypovolemic non-acute hyponatremia arising from a variety of etiologies. 240 (120 in each group) patients are to be enrolled randomly into Tolvaptan group or placebo group. Subjects in Tolvaptan group will receive standard therapy + Tolvaptan (15-60mg/day), while those in control group receiving standard therapy + placebo. The starting dose of tolvaptan is 15mg and it could be titrated up to 30mg and then,if necessary, to the maximum of 60mg according to a certain titration scheme based on patients' response of serum sodium level. The study includes a 2-day screening period from day -2 to day -1, 7-day inpatient study treatment (day 1 to day 7 ). After study treatment, subjects will be Followed-up on safety events on day 14 - 16. The Primary Efficacy Variable is the change of serum sodium from baseline. For patients with Congestive Heart Failure (CHF) or hepatic cirrhosis, change of body weight, fluid balance and symptoms improvement of CHF and hepatic edema will be assessed as secondary efficacy variables.

Conditions

Hypovolemic Hyponatremia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tolvaptan

Group Type: EXPERIMENTAL

Tolvaptan

Intervention Type: DRUG

Tablet;15mg/tab;15/30/60mg/day for 7days Plus conventional therapy according to each patient's underlying disease, such as congestive heart failure, hepatic cirrhosis and SIADH or others.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo plus conventional therapy according to each patient's underlying disease, such as congestive heart failure, hepatic cirrhosis and SIADH or others.

Interventions

Tolvaptan

Tablet;15mg/tab;15/30/60mg/day for 7days Plus conventional therapy according to each patient's underlying disease, such as congestive heart failure, hepatic cirrhosis and SIADH or others.

Intervention Type: DRUG

Placebo

placebo plus conventional therapy according to each patient's underlying disease, such as congestive heart failure, hepatic cirrhosis and SIADH or others.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Informed consent.

2. Age:18～75 (when informed consent is obtained)，male or female.

3. Non-hypovolemic and non acute hyponatremia with a Serum sodium < 135mEq/L before randomization. (main underlying diseases include CHF, hepatic cirrhosis with edema, SIADH and others)

4. In-patient subjects.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Otsuka Beijing Research Institute

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wenling Zhu

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Feng Gu

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Jidong Jia

Role: PRINCIPAL_INVESTIGATOR

Beijing Friendship Hospital

Locations

Department of Cardiology, the Third Xiangya Hospital, Central South University

Changsha, Hunan, China

Department of Cardiology, Xiangya Hospital, Central South University

Changsha, Hunan, China

Cardiology, Jilin University Second Hospital

Changchun, Jilin, China

Endocrinology, West China Hospital Sichuan University

Chengdu, Sichuan, China

Cardiology / Endocrinology, Peking Union Medical College Hospital

Beijing, , China

Cardiology / Hepatology, Beijing Friendship Hospital

Beijing, , China

Cardiology/Endocrinology/Infection, Beijing University First Hospital

Beijing, , China

Endocrinology, No. 301 hospital

Beijing, , China

Hepatology, Beijing Renmin Hospital

Beijing, , China

Hepatology/Endocrinology, Chongqing Medical University Second Hospital

Chongqing, , China

Hepatology / Endocrinology, Shanghai Changzheng Hospital

Shanghai, , China

Cardiology, Tianjin Medical University Second Hospital

Tianjin, , China

Endocrinology, Tianjin General Hospital

Tianjin, , China

Countries

China

References

Wang S, Zhang X, Han T, Xie W, Li Y, Ma H, Liebe R, Weng H, Ding HG. Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia. BMC Gastroenterol. 2018 Sep 4;18(1):137. doi: 10.1186/s12876-018-0857-0.

Reference Type: DERIVED

PMID: 30180806 (View on PubMed)

Chen S, Zhao JJ, Tong NW, Guo XH, Qiu MC, Yang GY, Liu ZM, Ma JH, Zhang ZW, Gu F. Randomized, double blinded, placebo-controlled trial to evaluate the efficacy and safety of tolvaptan in Chinese patients with hyponatremia caused by SIADH. J Clin Pharmacol. 2014 Dec;54(12):1362-7. doi: 10.1002/jcph.342.

Reference Type: DERIVED

PMID: 24906029 (View on PubMed)

Other Identifiers

156-07-802-01

Identifier Type: -

Identifier Source: org_study_id