Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of the Effects of Titrated Oral Tolvaptan Tablets in Patients With Hyponatremia

Date de début de l'étude : 1 avril 2003

Inclusion Criteria * Hyponatremia in euvolemic or hypervolemic states, defined as serum sodium \<135 mEq/L prior to randomization. * Able to give Informed Consent Exclusion Criteria * 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. 10) 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 BPH if non-obstructive. * Previous participation in another clinical drug trial within the past 30 days. * Previous participation in this or any other tolvaptan clinical trial. * Terminally ill or moribund condition with little chance of short term survival. * Serum creatinine \>3.5 mg/dL. * Serum sodium \<120 mEq/L with associated neurologic impairment, i.e. symptoms such as apathy, confusion, seizures. * Patients with progressive or episodic neurologic disease such as multiple sclerosis or history of multiple strokes. * Child-Pugh score greater than 10 (unless approved) * Patients receiving intravenous fluids at a rate greater than KVO (Keep Vein Open). * Hyponatremia due to lab artifacts * Patients receiving AVP or its analogs for treatment of any condition. * Patients receiving within 7 days of randomization, other medications for treatment of hyponatremia specifically: demeclocycline, lithium carbonate or urea * Patients likely requiring IV saline for correction of symptomatic or asymptomatic severe hyponatremia during the course of the study. * Severe pulmonary artery hypertension * Hyponatremia should not be the result of any medication that can safely be withdrawn