title: A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis.
abstract: BACKGROUND
  Genz-644470 is a new, nonabsorbed phosphate binding polymer. In an in vitro competitive phosphate binding assay, Genz-644470 bound significantly more phosphate per gram than sevelamer. As a consequence, this clinical study evaluated the ability of Genz-644470 to lower serum phosphorus in patients on hemodialysis and compared serum phosphorus lowering of Genz-644470 with sevelamer carbonate and placebo. Because three different fixed doses of Genz-644470 and sevelamer carbonate were used, phosphate-lowering dose-responses of each agent were also analyzed.
  
  
  METHODS
  A randomized, double-blind, dose-ranging study was conducted. After a 2-week phosphate binder washout, 349 hyperphosphatemic (serum phosphorus >5.5 mg/dL) hemodialysis patients were randomized to one of seven fixed-dose groups: placebo, Genz-644470 2.4 g/day, Genz-644470 4.8 g/day, Genz-644470 7.2 g/day, sevelamer carbonate 2.4 g/day, sevelamer carbonate 4.8 g/day, or sevelamer carbonate 7.2 g/day. Indicated total daily doses were administered in fixed divided doses three times a day with meals for 3 weeks. The change in serum phosphorus during the treatment period and its dose-response patterns were assessed.
  
  
  RESULTS
  Dose-dependent reductions in serum phosphorus were observed with both Genz-644470 and sevelamer carbonate. Serum phosphorus-lowering responses to fixed doses of sevelamer carbonate and Genz-644470 were enhanced in a roughly linear fashion with increasing doses over a threefold range after 3 weeks of treatment. Genz-644470 did not show any advantage in phosphorus lowering per gram of binder compared with sevelamer carbonate. Overall toler-ability was similar between active treatment groups. The tolerability of sevelamer carbonate was consistent with prior studies and with the established safety profile of sevelamer.
  
  
  CONCLUSIONS
  Both Genz-644470 and sevelamer carbonate effectively lowered serum phosphate levels in a dose-dependent fashion in patients with chronic kidney disease on hemodialysis. However, Genz-644470 did not provide any advantage over sevelamer carbonate in phosphate lowering in vivo, as had been demonstrated in vitro.
authors.affiliation: South Carolina Nephrology and Hypertension Center Inc., Orangeburg, SC, USA.
authors.forename: Moustafa
authors.initials: M
authors.lastname: Moustafa
authors.affiliation: Kidney Specialists of Southern Nevada, Las Vegas, NV, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lehrner
authors.affiliation: Michigan Kidney Consultants, Pontiac, MI, USA.
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Saghir
authors.affiliation: Kidney Care Associates, LLC, Augusta, GA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Smith
authors.affiliation: Genzyme, a Sanofi company, Cambridge, MA, USA.
authors.forename: Sunita
authors.initials: S
authors.lastname: Goyal
authors.affiliation: Genzyme, a Sanofi company, Cambridge, MA, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Dillon
authors.affiliation: Genzyme, a Sanofi company, Cambridge, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hunter
authors.affiliation: Genzyme, a Sanofi company, Cambridge, MA, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Holmes-Farley
keywords: clinical trial; hemodialysis; serum phosphorus; sevelamer carbonate
references.citation: Clin Nephrol. 2007 Dec;68(6):386-91
references.pmid: 18184521
references.citation: Nephrol Dial Transplant. 2009 Dec;24(12):3794-9
references.pmid: 19666658
references.citation: Nephrol Dial Transplant. 2004 Mar;19 Suppl 1:i19-24
references.pmid: 15126650
references.citation: Nephrol Dial Transplant. 2014 Jan;29(1):152-60
references.pmid: 24151017
references.citation: Clin J Am Soc Nephrol. 2008 Jul;3(4):1125-30
references.pmid: 18450923
references.citation: Nephrol Dial Transplant. 1997 Aug;12(8):1640-4
references.pmid: 9269642
references.citation: Clin Nephrol. 2004 Sep;62(3):193-201
references.pmid: 15481851
references.citation: Clin Nephrol. 2009 Oct;72(4):252-8
references.pmid: 19825330
references.citation: Nephrol Dial Transplant. 1997 May;12(5):961-4
references.pmid: 9175050
references.citation: Am J Kidney Dis. 1997 Jan;29(1):66-71
references.pmid: 9002531
references.citation: Nephrol Dial Transplant. 1998 Sep;13(9):2303-10
references.pmid: 9761513
references.citation: Kidney Int. 2005 Mar;67(3):1179-87
references.pmid: 15698460
references.citation: Am J Kidney Dis. 2010 Feb;55(2):307-15
references.pmid: 20042256