Moustafa Moustafa, Lehrner Lawrence, Al-Saghir Fahd, Smith Mark, Goyal Sunita, Dillon Maureen, Hunter John, Holmes-Farley Randy
South Carolina Nephrology and Hypertension Center Inc., Orangeburg, SC, USA.
Kidney Specialists of Southern Nevada, Las Vegas, NV, USA.
Int J Nephrol Renovasc Dis. 2014 Apr 7;7:141-52. doi: 10.2147/IJNRD.S56217. eCollection 2014.
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.
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.
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.
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.
Genz-644470是一种新型的、不被吸收的磷酸盐结合聚合物。在一项体外竞争性磷酸盐结合试验中，Genz-644470每克结合的磷酸盐明显多于司维拉姆。因此，本临床研究评估了Genz-644470降低血液透析患者血清磷的能力，并将Genz-644470与碳酸司维拉姆和安慰剂降低血清磷的效果进行了比较。由于使用了三种不同的Genz-644470和碳酸司维拉姆固定剂量，还分析了每种药物降低磷酸盐的剂量反应。
进行了一项随机、双盲、剂量范围研究。在为期2周的磷酸盐结合剂洗脱期后，349名高磷血症（血清磷>5.5mg/dL）血液透析患者被随机分为七个固定剂量组之一：安慰剂组、Genz-644470 2.4g/天组、Genz-644470 4.8g/天组、Genz-644470 7.2g/天组、碳酸司维拉姆2.4g/天组、碳酸司维拉姆4.8g/天组或碳酸司维拉姆7.2g/天组。规定的每日总剂量以固定的分次剂量，在进餐时每日三次给药，持续3周。评估治疗期间血清磷的变化及其剂量反应模式。
Genz-644470和碳酸司维拉姆均观察到血清磷呈剂量依赖性降低。治疗3周后，随着剂量在三倍范围内增加，碳酸司维拉姆和Genz-644470对固定剂量的血清磷降低反应大致呈线性增强。与碳酸司维拉姆相比，Genz-644470每克结合剂在降低磷方面未显示出任何优势。活性治疗组之间的总体耐受性相似。碳酸司维拉姆的耐受性与先前的研究以及司维拉姆已确立的安全性概况一致。
Genz-644470和碳酸司维拉姆均能以剂量依赖性方式有效降低慢性肾脏病血液透析患者的血清磷酸盐水平。然而，正如在体外所证明的那样，Genz-644470在体内降低磷酸盐方面并未比碳酸司维拉姆具有任何优势。
