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

This study has been completed.
Sponsor:
Collaborator:
Otsuka Pharmaceutical Co., Ltd.
Information provided by:
Otsuka Beijing Research Institute
ClinicalTrials.gov Identifier:
NCT00664014
First received: April 14, 2008
Last updated: March 5, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Hypovolemic Hyponatremia
Drug: Tolvaptan
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Multicenter, Placebo-controlled (Standard Therapy + Placebo), Phase 2 Efficacy and Safety Study of the Tolvaptan Tablets in Patients With Non-hypovolemic Non-acute Hyponatremia

Resource links provided by NLM:


Further study details as provided by Otsuka Beijing Research Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 4 or 7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: May 2008
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tolvaptan Drug: 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.
Placebo Comparator: Placebo Drug: Placebo
placebo plus conventional therapy according to each patient's underlying disease, such as congestive heart failure, hepatic cirrhosis and SIADH or others.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00664014

Locations
China, Human
Department of Cardiology, the Third Xiangya Hospital, Central South University
Changsha, Human, China
China, Hunan
Department of Cardiology, Xiangya Hospital, Central South University
Changsha, Hunan, China
China, Jinlin
Cardiology, Jilin University Second Hospital
Changchun, Jinlin, China
China, Sichuan
Endocrinology, West China Hospital Sichuan University
Chengdu, Sichuan, China
China
Cardiology / Hepatology, Beijing Friendship Hospital
Beijing, China
Cardiology/Endocrinology/Infection, Beijing University First Hospital
Beijing, China
Cardiology / Endocrinology, Peking Union Medical College Hospital
Beijing, China
Hepatology, Beijing Renmin Hospital
Beijing, China
Endocrinology, No. 301 hospital
Beijing, China
Hepatology/Endocrinology, Chongqing Medical University Second Hospital
Chongqing, China
Hepatology / Endocrinology, Shanghai Changzheng Hospital
Shanghai, China
Endocrinology, Tianjin General Hospital
Tianjin, China
Cardiology, Tianjin Medical University Second Hospital
Tianjin, China
Sponsors and Collaborators
Otsuka Beijing Research Institute
Otsuka Pharmaceutical Co., Ltd.
Investigators
Principal Investigator: Wenling Zhu Peking Union Medical College Hospital
Principal Investigator: Feng Gu Peking Union Medical College Hospital
Principal Investigator: Jidong Jia Beijing Friendship Hospital
  More Information

No publications provided

Responsible Party: Yong Jin / Project Manager, Otsuka Beijing Research Institute
ClinicalTrials.gov Identifier: NCT00664014     History of Changes
Other Study ID Numbers: 156-07-802-01
Study First Received: April 14, 2008
Last Updated: March 5, 2010
Health Authority: China: Food and Drug Administration

Keywords provided by Otsuka Beijing Research Institute:
hyponatremia
Non-acute and non hypovolemic hyponatremia

Additional relevant MeSH terms:
Hyponatremia
Metabolic Diseases
Water-Electrolyte Imbalance

ClinicalTrials.gov processed this record on October 23, 2014