Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia.

Published

Journal Article

Senicapoc, a novel Gardos channel inhibitor, limits solute and water loss, thereby preserving sickle red blood cell (RBC) hydration. Because hemoglobin S polymerization is profoundly influenced by intracellular hemoglobin concentration, senicapoc could improve sickle RBC survival. In a 12-week, multicenter, phase 2, randomized, double-blind, dose-finding study, we evaluated senicapoc's safety and its effect on hemoglobin level and markers of RBC hemolysis in sickle cell anemia patients. The patients were randomized into 3 treatment arms: placebo; low-dose (6 mg/day) senicapoc; and high-dose (10 mg/day) senicapoc. For the primary efficacy end point (change in hemoglobin level from baseline), the mean response to high-dose senicapoc treatment exceeded placebo (6.8 g/L [0.68 g/dL] vs 0.1 g/L [0.01 g/dL], P < .001). Treatment with high-dose senicapoc also produced significant decreases in such secondary end points as percentage of dense RBCs (-2.41 vs -0.08, P < .001); reticulocytes (-4.12 vs -0.46, P < .001); lactate dehydrogenase (-121 U/L vs -15 U/L, P = .002); and indirect bilirubin (-1.18 mg/dL vs 0.12 mg/dL, P < .001). Finally, senicapoc was safe and well tolerated. The increased hemoglobin concentration and concomitant decrease in the total number of reticulocytes and various markers of RBC destruction following senicapoc administration suggests a possible increase in the survival of sickle RBCs. This study is registered at http://clinicaltrials.gov as NCT00040677.

Full Text

Duke Authors

Cited Authors

  • Ataga, KI; Smith, WR; De Castro, LM; Swerdlow, P; Saunthararajah, Y; Castro, O; Vichinsky, E; Kutlar, A; Orringer, EP; Rigdon, GC; Stocker, JW; ICA-17043-05 Investigators,

Published Date

  • April 2008

Published In

Volume / Issue

  • 111 / 8

Start / End Page

  • 3991 - 3997

PubMed ID

  • 18192510

Pubmed Central ID

  • 18192510

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2007-08-110098

Language

  • eng