Thadhani Ravi, Zella Julia B, Knutson Danielle C, Blaser William J, Plum Lori A, Clagett-Dame Margaret, Buck Raymond D, DeLuca Hector F
Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA.
Am J Nephrol. 2017;45(1):40-48. doi: 10.1159/000452680. Epub 2016 Nov 24.
Vitamin D analogs and calcimimetics are used to manage secondary hyperparathyroidism (SHPT) in dialysis patients. DP001 is an oral vitamin D analog that suppresses parathyroid hormone (PTH) in uremic rats, osteopenic women, and hemodialysis patients. The safety and effectiveness of DP001 suppressing PTH in dialysis patients previously managed with active vitamin D with or without a calcimimetic are presented.
A multicenter, randomized, double-blind study compared DP001 to placebo in hemodialysis patients with serum-intact PTH (iPTH) ≥300 pg/ml. The primary efficacy endpoint was the proportion of patients achieving 2 consecutive ≥30% decreases in iPTH levels during the 12 weeks of treatment. Calcium, phosphorus, calcium × phosphorus product and safety were also evaluated. The responses to DP001 were compared in patients previously treated with both active vitamin D and a calcimimetic to those previously on active vitamin D alone.
Sixty-two patients were randomized (n = 34 DP001; n = 28 placebo). At week 12, 78% of all DP001-treated patients and 7% of all placebo-treated patients achieved the primary endpoint (p < 0.0001); iPTH fell 45% in the DP001 group and increased 37% in the placebo group. No patient exceeded the safety threshold of 2 consecutively corrected serum calcium levels ≥11.0 mg/dl. Patients previously on cinacalcet plus active vitamin D also responded to DP001 (n = 10) resulting in a 55% decrease in iPTH, while those on placebo (n = 9) increased by 70%.
DP001 safely and effectively suppressed iPTH in hemodialysis patients with SHPT that were previously managed with active vitamin D alone or with a calcimimetic (www.clinicaltrials.gov, NCT01922843).
维生素D类似物和拟钙剂用于治疗透析患者的继发性甲状旁腺功能亢进（SHPT）。DP001是一种口服维生素D类似物，可抑制尿毒症大鼠、骨质疏松女性和血液透析患者的甲状旁腺激素（PTH）。本文介绍了DP001在先前使用活性维生素D（加或不加拟钙剂）治疗的透析患者中抑制PTH的安全性和有效性。
一项多中心、随机、双盲研究将DP001与安慰剂在血清完整PTH（iPTH）≥300 pg/ml的血液透析患者中进行比较。主要疗效终点是在12周治疗期间iPTH水平连续2次下降≥30%的患者比例。还评估了钙、磷、钙×磷乘积和安全性。将先前同时接受活性维生素D和拟钙剂治疗的患者对DP001的反应与先前仅接受活性维生素D治疗的患者进行比较。
62例患者被随机分组（n = 34接受DP001治疗；n = 28接受安慰剂治疗）。在第12周时，所有接受DP001治疗的患者中有78%达到主要终点，而所有接受安慰剂治疗的患者中这一比例为7%（p < 0.0001）；DP001组iPTH下降45%，安慰剂组上升37%。没有患者连续2次校正血清钙水平超过11.0 mg/dl的安全阈值。先前接受西那卡塞加活性维生素D治疗的患者对DP001也有反应（n = 10），iPTH下降55%，而接受安慰剂治疗的患者（n = 9）上升70%。
DP001在先前单独使用活性维生素D或与拟钙剂治疗的SHPT血液透析患者中安全有效地抑制了iPTH（www.clinicaltrials.gov，NCT01922843）。
