Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Apr 7:7:141-52.
doi: 10.2147/IJNRD.S56217. eCollection 2014.

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  1 , Lawrence Lehrner  2 , Fahd Al-Saghir  3 , Mark Smith  4 , Sunita Goyal  5 , Maureen Dillon  5 , John Hunter  5 , Randy Holmes-Farley  5
Affiliations

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 et al. Int J Nephrol Renovasc Dis. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Competitive phosphate binding of sevelamer carbonate and Genz-644470 in vitro.
Figure 2
Figure 2
CONSORT diagram of patient disposition, all randomized patients.
Figure 3
Figure 3
Mean (± standard deviation) change in serum phosphorus from baseline to end of treatment (day 22). Note: Data for the placebo group are presented for comparison purposes.
Figure 4
Figure 4
Changes from baseline in serum phosphorus at each visit following treatment with Genz-644470 (A) and sevelamer (B).
See this image and copyright information in PMC

References

    1. Delmez J, Block G, Robertson J, et al. A randomized, double-blind, crossover design study of sevelamer hydrochloride and sevelamer carbonate in patients on hemodialysis. Clin Nephrol. 2007;68(6):386–391. - PubMed
    1. Fan S, Ross C, Mitra S, et al. A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis. Nephrol Dial Transplant. 2009;24(12):3794–3799. - PMC - PubMed
    1. Ketteler M, Rix M, Fan S, et al. Efficacy and tolerability of sevelamer carbonate in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis. Clin J Am Soc Nephrol. 2008;3(4):1125–1130. - PMC - PubMed
    1. Young EW, Albert JM, Satayathum S, et al. Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. Kidney Int. 2005;67(3):1179–1187. - PubMed
    1. Tomasello S, Dhupar S, Sherman RA. Phosphate binders, K/DOQI guidelines, and compliance: the unfortunate reality. Dial Transplant. 2004;33(5):236–242.