医学
耐受性
塞维莱默
胃肠病学
血液透析
磷酸盐粘合剂
临床终点
不利影响
外科
内科学
随机对照试验
肾脏疾病
高磷血症
作者
Bing Zhuang,Liangying Gan,Bin Liu,Weijie Yuan,Ming Shi,Ai Peng,Lihua Wang,Xiaolan Chen,Tongqiang Liu,Shiying Zhang,Song Wang,Dianshuai Gao,Baoxing Wang,Huixiao Zheng,Changhua Liu,Yang Luo,Hong Yao,Hongli Lin,Yiwen Li,Qin He,Feng Zheng,Ping Luo,Gang Li,Wei Lü,Kanghui Li,Junwei Yang,Yingxue Cathy Liu,Zhizheng Zhang,Xin Li,Weifeng Zhang,Li Zuo
摘要
Abstract Background VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). Methods In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. Results The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change −2.0 mg/dL; 95% confidence interval −2.7, −1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change −1.6 (−2.2, −1.0), −1.8 (−2.4, −1.2), and −1.4 (−2.2, −0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. Conclusion VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300