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Abstract: Poster Presentations |

EFFICACY AND SAFETY OF CONIVAPTAN, A VASOPRESSIN V1A- AND V2-RECEPTOR ANTAGONIST, DURING PHASE 3 TRIALS OF PATIENTS WITH EUVOLEMIC OR HYPERVOLEMIC HYPONATREMIA FREE TO VIEW

Joseph G. Verbalis, MD*; Steven Rosansky, MD; Lynne E. Wagoner, MD; Bruce McNutt, MD; Bo Yan, PhD
Author and Funding Information

Georgetown University, Washington, DC


Chest


Chest. 2007;132(4_MeetingAbstracts):562b. doi:10.1378/chest.132.4_MeetingAbstracts.562b
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Abstract

PURPOSE: Hyponatremia is the most common electrolyte disorder and is often associated with elevated levels of arginine vasopressin (AVP). Two clinical trials evaluated the efficacy and safety of conivaptan, a novel AVP V1A- and V2-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia.

METHODS: During the randomized controlled trial (RCT), patients were assigned to placebo or conivaptan 40 or 80 mg/d for 4 days after receiving an IV loading dose of placebo or conivaptan 20 mg on day 1. During the open-label study (OLS), all patients received a loading dose of conivaptan 20 mg on day 1 followed by conivaptan 20 or 40 mg/d as a continuous infusion for 4 days. Efficacy assessments included the change from baseline in serum Na+ concentration ([Na+]), as measured by the area under the serum [Na+]–time curve (AUC, the 1° measure), absolute change from baseline in serum [Na+], and others (Table). Safety was determined according to physical examination results, vital signs, clinical laboratory parameters, and adverse events (AEs).

RESULTS: In the RCT (n=84), the baseline-adjusted AUC was significantly greater with conivaptan 40 and 80 mg/d than with placebo (P≤;.0001). Compared with placebo, both doses of conivaptan were associated with a significantly shorter median time to a ≥4 mEq/L increase in serum [Na+], a significantly greater mean serum [Na+] increase at day 4, and a significantly higher percentage of patients demonstrating a ≥6 mEq/L increase in serum [Na+] or normal serum [Na+] (serum [Na+] ≥135 mEq/L). Similar results were observed in the OLS (n=251), with prompt and clinically relevant increases in serum [Na+] and most patients demonstrating a serum [Na+] increase ≥6 mEq/L or normal serum [Na+]. In both trials, the most common AEs were related to infusion-site reactions.

CONCLUSION: Conivaptan was effective and well tolerated in patients with hypervolemic or euvolemic hyponatremia.

CLINICAL IMPLICATIONS: Conivaptan provides a novel approach in the treatment of hypervolemic or euvolemic hyponatremia in hospitalized patients.

DISCLOSURE: Joseph Verbalis, No Product/Research Disclosure Information; Grant monies (from industry related sources) Joseph G. Verbalis, Astellas Pharma US, Inc; Employee Bruce McNutt, Bo Yan, Astellas Pharma US, Inc.; Consultant fee, speaker bureau, advisory committee, etc. Joseph G. Verbalis is a consultant for Astellas Pharma US, Inc., Otsuka Pharmaceutical Co., Ltd., and Sanofi-Aventis, and has received fees for speaking from Astellas Pharma US, Inc.

Wednesday, October 24, 2007

12:30 PM - 2:00 PM


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