Study of Ascending Levels of Tolvaptan in Hyponatremia

NCT00201994 | Completed Phase 3

• 1 other identifier: 156-03-238
• Study Type: interventional
• Target: 243
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to determine whether tolvaptan can safely and effectively return the body's balance of sodium and water toward normal and to characterize and quantify the potential clinical benefits of this treatment.

Conditions

Hyponatremia

Keywords

Sodium; Syndrome of inappropriate antidiuretic hormone secretion; SIADH; Vasopressin; Congestive heart failure; CHF; Cirrhosis; salt; water; electrolyte

Study Arms (2)

Tolvaptan

EXPERIMENTAL

Participants received tolvaptan orally once a day for 30 days. Initially participants received tolvaptan 15 mg and were forced titrated to 30 mg and 60 mg based on the change in their serum sodium level. Titration occurred if the serum sodium level increased by \< 5 mEq/L (mmol/L) from the previous measurement 22-24 hours earlier and was ≤ 135 mEq/L (mmol/L).

Drug: Tolvaptan

Placebo

PLACEBO COMPARATOR

Participants received placebo orally once a day for 30 days.

Drug: Placebo

Interventions

Tolvaptan DRUG

Tolvaptan was supplied as tablets.

Also known as: Samsca, OPC-41061

Tolvaptan

Placebo DRUG

Placebo was supplied as tablets.

Placebo

Eligibility Criteria

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

You may qualify if:

• Hyponatremia in euvolemic or hypervolemic states, defined as serum sodium \< 135 mEq/L prior to randomization.
• Able to give Informed Consent.

You may not qualify if:

• Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods.
• Hyponatremia in hypovolemic states.
• Acute and transient hyponatremia associated with head trauma or post-operative state.
• Hyponatremia due to uncontrolled hypothyroidism or uncontrolled adrenal insufficiency.
• Cardiac surgery within 30 days of potential study enrollment, excluding percutaneous coronary interventions.
• History of a myocardial infarction within 30 days of potential study enrollment.
• History of sustained ventricular tachycardia or ventricular fibrillation within 30 days, unless in the presence of an automatic implantable cardioverter defibrillator.
• Severe angina including angina at rest or at slight exertion and/or unstable angina.
• History of a cerebrovascular accident within the last 30 days.
• Subjects with psychogenic polydipsia may not be included, however subjects with other psychiatric illness may be included.
• Systolic arterial blood pressure \< 90 mmHg.
• History of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives (such as benazepril).
• History of drug or medication abuse within the past year,or current alcohol abuse.
• Uncontrolled diabetes mellitus defined as fasting glucose \> 300mg/dL.
• Urinary tract obstruction except benign prostatic hyperplasia (BPH) if non-obstructive.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• Otsuka Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Universitatskilinikum Carl

Gustav Carus, Dresden, D-01307, Germany

Location

Related Publications (3)

• Lee MY, Kang HJ, Park SY, Kim HL, Han E, Lee EK. Cost-effectiveness of tolvaptan for euvolemic or hypervolemic hyponatremia. Clin Ther. 2014 Sep 1;36(9):1183-94. doi: 10.1016/j.clinthera.2014.07.010. Epub 2014 Aug 21.

  PMID: 25151571 DERIVED

• Cardenas A, Gines P, Marotta P, Czerwiec F, Oyuang J, Guevara M, Afdhal NH. Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis. J Hepatol. 2012 Mar;56(3):571-8. doi: 10.1016/j.jhep.2011.08.020. Epub 2011 Oct 23.

  PMID: 22027579 DERIVED

• Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, Orlandi C; SALT Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006 Nov 16;355(20):2099-112. doi: 10.1056/NEJMoa065181. Epub 2006 Nov 14.

  PMID: 17105757 DERIVED

MeSH Terms

Conditions

Hyponatremia; Inappropriate ADH Syndrome; Diabetes Insipidus; Heart Failure; Fibrosis

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Frank Czerwiec, MD, PhD

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 20, 2005
• Study Start: November 1, 2003
• Primary Completion: July 1, 2005
• Study Completion: July 1, 2005
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Locations

DE (1)