title: Comparison of paricalcitol with maxacalcitol injection in Japanese hemodialysis patients with secondary hyperparathyroidism.
abstract: Secondary hyperparathyroidism (SHPT) is one of the major complications of chronic kidney disease (CKD) and is associated with elevated serum intact parathyroid hormone (iPTH). Calcitriol, a non-selective vitamin D receptor agonist (VDRA) that suppresses iPTH is used for SHPT treatment, but its use is frequently complicated by hypercalcemia. Paricalcitol, a selective VDRA, demonstrated efficacy in iPTH suppression compared to maxacalcitol in a Phase 2 study (M11-609) in Japanese subjects. The current larger Phase 3 study (M11-517), evaluated the efficacy of intravenous paricalcitol injection compared to intravenous maxacalcitol injection with respect to iPTH and calcium control using a non-inferiority primary endpoint. In this double-blind, double-dummy, parallel-group study, eligible Japanese CKD subjects with SHPT on hemodialysis were randomized 1:1 to receive intravenous paricalcitol or intravenous maxacalcitol injections for 12 weeks. Dynamic allocation of subjects on the basis of screening iPTH levels was used to ensure equal distribution of subjects with iPTH <500 pg/mL and ≥500 pg/mL into the two treatment groups. 255 subjects were randomized to receive paricalcitol (N = 127) or maxacalcitol (N = 128). Primary efficacy analysis indicated that 27.7% in the paricalcitol group vs. 30.5% in the maxacalcitol group (95% CI -14.34% to 8.79%, P = 0.353) achieved target iPTH in the last 3 weeks without hypercalcemia during treatment, failing to achieve the non-inferiority margin of -5% that was set based upon agreement with the PMDA. Both intravenous paricalcitol and maxacalcitol were effective in reducing iPTH and provided similar safety profiles; however, non-inferiority for paricalcitol vs. maxacalcitol was not demonstrated.
authors.affiliation: Showa University School of Medicine, Tokyo, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
authors.affiliation: Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Akiba
authors.affiliation: Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hirakata
authors.affiliation: Showa University Northern Yokohama Hospital, Yokohama, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Kinugasa
authors.affiliation: Nagoya Daini Red Cross Hospital, Aichi, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tominaga
authors.affiliation: Tokai University School of Medicine, Isehara, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
authors.affiliation: Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yokoyama
authors.affiliation: Clinical Statistics, AbbVie, North Chicago, IL, USA.
authors.forename: Wuyan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Renal Clinical Development, AbbVie, North Chicago, IL, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Linde
authors.affiliation: Shinrakuen Hospital, Niigata, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000368:Aged; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002118:Calcium / Q000097:blood; D004311:Double-Blind Method; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D018167:Receptors, Calcitriol / Q000819:agonists; D006435:Renal Dialysis / Q000379:methods*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000628:therapy
chemical_list: D004872:Ergocalciferols; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; C084656:paricalcitol; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium
keywords: Chronic Kidney Disease; Maxacalcitol; Paricalcitol; Secondary Hyperparathyroidism; Vitamin D