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

NCT00664014 | Completed Phase 2

• 1 other identifier: 156-07-802-01
• Study Type: interventional
• Target: 241
• Locations: 1 country
• Sites: 13

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

Keywords

hyponatremia; Non-acute and non hypovolemic hyponatremia

Outcome Measures

Primary Outcomes (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.

  4 and 7 days

Secondary Outcomes (1)

• For CHF and hepatic edema patients, improvement of symptoms and relevant physical examination measures or ultrasound test findings . Other secondary efficacy variables on blood serum sodium, fluid balance or body weight change.

  4 or 7 days

Study Arms (2)

Tolvaptan

EXPERIMENTAL

Drug: Tolvaptan

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tolvaptan 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.

Tolvaptan

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent.
• Age:18～75 (when informed consent is obtained)，male or female.
• 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)
• In-patient subjects.

Sponsors & Collaborators

• Otsuka Beijing Research Institute: lead
• Otsuka Pharmaceutical Co., Ltd.: collaborator

Study Sites (13)

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

Changsha, Hunan, China

Location

Department of Cardiology, Xiangya Hospital, Central South University

Changsha, Hunan, China

Location

Cardiology, Jilin University Second Hospital

Changchun, Jilin, China

Location

Endocrinology, West China Hospital Sichuan University

Chengdu, Sichuan, China

Location

Cardiology / Endocrinology, Peking Union Medical College Hospital

Beijing, China

Location

Cardiology / Hepatology, Beijing Friendship Hospital

Beijing, China

Location

Cardiology/Endocrinology/Infection, Beijing University First Hospital

Beijing, China

Location

Endocrinology, No. 301 hospital

Beijing, China

Location

Hepatology, Beijing Renmin Hospital

Beijing, China

Location

Hepatology/Endocrinology, Chongqing Medical University Second Hospital

Chongqing, China

Location

Hepatology / Endocrinology, Shanghai Changzheng Hospital

Shanghai, China

Location

Cardiology, Tianjin Medical University Second Hospital

Tianjin, China

Location

Endocrinology, Tianjin General Hospital

Tianjin, China

Location

Related Publications (2)

• 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.

  PMID: 30180806 DERIVED

• 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.

  PMID: 24906029 DERIVED

MeSH Terms

Conditions

Hyponatremia

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Wenling Zhu

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• Feng Gu

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• Jidong Jia

  Beijing Friendship Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2008
• First Posted: April 22, 2008
• Study Start: May 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

CN (13)