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Blood, 15 April 2008, Vol. 111, No. 8, pp. 3991-3997. Prepublished online as a Blood First Edition Paper on January 11, 2008; DOI 10.1182/blood-2007-08-110098. This Article Full Text Full Text (PDF) Supplemental Appendices All Versions of this Article: blood-2007-08-110098v1 111/8/3991    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Ataga, K. I. Articles by Stocker, J. W. PubMed PubMed Citation Articles by Ataga, K. I. Articles by Stocker, J. W. Related Collections Clinical Trials and Observations Red Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia Kenneth I. Ataga1, Wally R. Smith2, Laura M. De Castro3, Paul Swerdlow4, Yogen Saunthararajah5, Oswaldo Castro6, Elliot Vichinsky7, Abdullah Kutlar8, Eugene P. Orringer1, Greg C. Rigdon9, Jonathan W. Stocker9, for the ICA-17043-05 Investigators 1 University of North Carolina, Chapel Hill; 2 Virginia Commonwealth University Medical Center, Richmond; 3 Duke University Medical Center, Durham, NC; 4 Wayne State University, Detroit, MI; 5 University of Illinois, Chicago; 6 Howard University, Washington, DC; 7 Children's Hospital of Oakland, CA; 8 Medical College of Georgia, Augusta; and 9 Icagen, Research Triangle Park, NC 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 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Gardos pathway to sickle cell therapies? Clinton H. Joiner Blood 2008 111: 3918-3919. [Full Text] [PDF] This article has been cited by other articles: Plugging the Leak in Sickle Cells Journal Watch Oncology and Hematology, May 6, 2008; 2008(506): 2 - 2. [Full Text]

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