Lixivaptan safely and effectively corrects serum sodium concentrations in hospitalized patients with euvolemic hyponatremia

• Published in: Kidney international Vol. 82; no. 11; pp. 1223 - 1230
• Main Authors: Abraham, William T., Hensen, Johannes, Gross, Peter A., Bichet, Daniel G., Josiassen, Richard C., Chafekar, DeoDatta S., Orlandi, Cesare
• Format: Journal Article
• Language: English
• Published: Basingstoke Elsevier Inc 01.12.2012; Nature Publishing Group; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Benzamides - adverse effects; Benzamides - therapeutic use; Biological and medical sciences; clinical trial; Double-Blind Method; Female; Hospitalization; Humans; hyponatremia; Hyponatremia - blood; Hyponatremia - drug therapy; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Pyrroles - adverse effects; Pyrroles - therapeutic use; Sodium - blood; Treatment Outcome; vasopressin; clinical trial; hyponatremia; vasopressin; Human; Hydroelectrolytic balance disorder; Nephrology; Hyponatremia; Hospitalization; Concentration; Lixivaptan; Neuropeptide; Inorganic element; Urology; Vasopressin; Metabolic disorder; Sodium; Neurohypophyseal hormone; Peptidergic receptor; V2 vasopressin receptor; Clinical trial; Serum; Antagonist
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.2012.275

Hyponatremia is a common electrolyte disorder associated with increased morbidity and mortality, particularly in the elderly. Lixivaptan, a new selective vasopressin V2-receptor antagonist, safely corrected serum sodium concentrations in phase II studies of patients with euvolemic hyponatremia. Here our multinational, double-blind, placebo-controlled, phase III study assessed the effect of lixivaptan on serum sodium concentrations in 106 initially hospitalized patients with euvolemic hyponatremia (serum sodium less than 130mmol/l). Of them, 52 were randomized to receive placebo and 54 received 50mg lixivaptan once daily and were then titrated to receive 25–100mg once daily depending on serum sodium concentration. Fluid restriction was at the investigator's discretion. Initial titration occurred in a monitored inpatient setting; patients were then treated as outpatients for a total of 30 days. The primary end point was the change in serum sodium concentration from baseline to day 7. Lixivaptan significantly increased the serum sodium concentration from baseline to day 7 (the primary end point) by 6.7mmol/l compared with placebo (4.5mmol/l; P=0.034). Importantly, the serum sodium concentration was normalized safely and more rapidly in patients receiving lixivaptan than placebo (P=0.004) and was well tolerated. After drug discontinuation, serum sodium concentrations decreased to near-baseline levels within 7 days. Thus, lixivaptan safely and effectively corrects serum sodium concentrations in patients with euvolemic hyponatremia.