A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis

Moustafa Moustafa; Lawrence Lehrner; Fahd Al-Saghir; Mark Smith; Sunita Goyal; Maureen Dillon; John Hunter; Randy Holmes-Farley

doi:10.2147/IJNRD.S56217

A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis

Int J Nephrol Renovasc Dis. 2014 Apr 7:7:141-52. doi: 10.2147/IJNRD.S56217. eCollection 2014.

Authors

Moustafa Moustafa¹, Lawrence Lehrner², Fahd Al-Saghir³, Mark Smith⁴, Sunita Goyal⁵, Maureen Dillon⁵, John Hunter⁵, Randy Holmes-Farley⁵

Affiliations

¹ South Carolina Nephrology and Hypertension Center Inc., Orangeburg, SC, USA.
² Kidney Specialists of Southern Nevada, Las Vegas, NV, USA.
³ Michigan Kidney Consultants, Pontiac, MI, USA.
⁴ Kidney Care Associates, LLC, Augusta, GA, USA.
⁵ Genzyme, a Sanofi company, Cambridge, MA, USA.

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.

Conclusion: 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.

Keywords: clinical trial; hemodialysis; serum phosphorus; sevelamer carbonate.