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

Blood
Kenneth I AtagaICA-17043-05 Investigators

Abstract

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 decre...Continue Reading

References

Mar 1, 1989·The American Journal of Physiology·R P HebbelW Foker
Dec 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·J HofrichterW A Eaton
Nov 9, 1973·Nature·J W EatonH S Jacob
Aug 8, 1996·The New England Journal of Medicine·M C WaltersK M Sullivan
Sep 11, 1997·The New England Journal of Medicine·H F Bunn
Nov 12, 2002·Nature Medicine·Christopher D ReiterMark T Gladwin
Apr 4, 2003·JAMA : the Journal of the American Medical Association·Martin H SteinbergMichael Terrin
Dec 1, 1958·Biochimica Et Biophysica Acta·G GARDOS
Feb 27, 2004·The New England Journal of Medicine·Mark T GladwinFrederick P Ognibene
Jun 29, 2006·British Journal of Haematology·Kenneth I AtagaEugene P Orringer
Oct 27, 2006·Pharmacotherapy·Kenneth I AtagaJonathan W Stocker

❮ Previous
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Citations

Nov 28, 2008·Pflügers Archiv : European journal of physiology·Ivica GrgicRalf Köhler
Nov 6, 2012·Journal of Medicinal Chemistry·Sharan K BagalNigel A Swain
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Ivica GrgicJoachim Hoyer
Feb 24, 2012·Current Opinion in Hematology·Pablo Bartolucci, Frédéric Galactéros
Jun 8, 2012·International Journal of Alzheimer's Disease·Izumi MaezawaHeike Wulff
Dec 4, 2012·American Journal of Respiratory Cell and Molecular Biology·Pierre-Olivier GirodetPatrick Berger
Mar 16, 2013·American Journal of Respiratory Cell and Molecular Biology·Zhi-Hua YuHong-Zhuan Chen
Aug 9, 2008·The Journal of Clinical Investigation·Kazuyoshi ToyamaHiroto Miura
Dec 17, 2009·Hematology·Kenneth I Ataga
Jan 7, 2014·PloS One·Katy M RoachPeter Bradding
Jan 1, 2009·Mediterranean Journal of Hematology and Infectious Diseases·Lucia De Franceschi
Mar 31, 2012·Future Medicinal Chemistry·A WickendenG Erdemli
Nov 7, 2013·Pflügers Archiv : European journal of physiology·Colin J Stoneking, Michael J Mason
Nov 22, 2014·Current Opinion in Nephrology and Hypertension·Chunling HuangXin-Ming Chen
Jan 9, 2010·Expert Opinion on Therapeutic Targets·Ralf KöhlerHeike Wulff
Nov 19, 2010·Expert Review of Hematology·Kleber Yotsumoto Fertrin, Fernando Ferreira Costa
May 1, 2010·Expert Review of Clinical Pharmacology·Heike Wulff, Neil A Castle
Sep 29, 2009·Expert Opinion on Investigational Drugs·Sandy D Kotiah, Samir K Ballas
Nov 14, 2008·Expert Opinion on Pharmacotherapy·Winfred C Wang
Dec 30, 2014·Journal of Cellular Physiology·Kristin FriebelElke Kunisch
May 21, 2009·Kidney International·Vicente E Torres, Peter C Harris
Aug 30, 2008·Kidney International·Seth L Alper
Sep 20, 2011·Experimental Hematology·Iwona Hirschler-LaszkiewiczBarbara A Miller
Dec 10, 2014·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Edward TrueloveUNKNOWN British Society for Blood and Marrow Transplantation (BSBMT)
Mar 5, 2010·Blood Cells, Molecules & Diseases·Marie-Claude DurpèsMarie-Dominique Hardy-Dessources
Mar 12, 2010·Advances in Chronic Kidney Disease·Vicente E Torres
Jul 14, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yi-Je ChenHeike Wulff
Nov 15, 2008·Pulmonary Pharmacology & Therapeutics·Jose F Perez-ZoghbiMichael J Sanderson
May 27, 2008·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·Y Beuzard
Aug 18, 2009·British Journal of Pharmacology·Peter Bradding, Heike Wulff
Feb 19, 2009·British Journal of Haematology·Jane Hankins, Banu Aygun
Apr 23, 2013·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·I Ashmole, P Bradding
Jun 10, 2011·British Journal of Haematology·Caterina P MinnitiGregory J Kato

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