title: A phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese haemodialysis patients.
abstract: BACKGROUND
  Secondary hyperparathyroidism (SHPT) is a major complication associated with chronic kidney disease. We evaluated the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, in Japanese haemodialysis patients with SHPT.
  
  
  METHODS
  In this phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study, etelcalcetide was administered three times per week at an initial dose of 5 mg, and subsequently adjusted to doses between 2.5 and 15 mg at 4-week intervals for 12 weeks. A total of 155 SHPT patients with serum intact parathyroid hormone (iPTH) levels ≥300 pg/mL were assigned to receive etelcalcetide (n = 78) or placebo (n = 77). The primary endpoint was the proportion of patients with decreased serum iPTH to the target range proposed by the Japanese Society for Dialysis Therapy (60-240 pg/mL). The major secondary endpoint was the proportion of patients with ≥30% reductions in serum iPTH from baseline.
  
  
  RESULTS
  The proportion of patients meeting the primary endpoint was significantly higher for etelcalcetide (59.0%) versus placebo (1.3%). Similarly, the proportion of patients meeting the major secondary endpoint was significantly higher for etelcalcetide (76.9%) versus placebo (5.2%). Serum albumin-corrected calcium, phosphorus and intact fibroblast growth factor-23 levels were decreased in the etelcalcetide group. Nausea, vomiting and symptomatic hypocalcaemia were mild with etelcalcetide. Serious adverse events related to etelcalcetide were not observed.
  
  
  CONCLUSIONS
  This study demonstrated the efficacy and safety of etelcalcetide. As the only available intravenous calcium-sensing receptor agonist, etelcalcetide is likely to provide a new treatment option for SHPT in haemodialysis patients.
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yokoyama
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shigematsu
authors.affiliation: Sekikawa Hospital, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Akiba
authors.affiliation: Clinical Development Planning.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Fujii
authors.affiliation: Clinical Development Planning.
authors.forename: Takuto
authors.initials: T
authors.lastname: Kuramoto
authors.affiliation: Data Science, Ono Pharmaceutical Co. Ltd, Osaka, Japan.
authors.forename: Motoi
authors.initials: M
authors.lastname: Odani
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000627:therapeutic use*; D010758:Phosphorus / Q000097:blood; D044169:Receptors, Calcium-Sensing / Q000819:agonists*; D006435:Renal Dialysis / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D055815:Young Adult
chemical_list: D010281:Parathyroid Hormone; D010455:Peptides; D044169:Receptors, Calcium-Sensing; D010758:Phosphorus; C583569:etelcalcetide hydrochloride; D002118:Calcium
keywords: CKD-MBD; calcium-sensing receptor agonist (calcimimetics); etelcalcetide (ONO-5163/AMG 416); placebo-controlled phase 3 study; secondary hyperparathyroidism