title: Treatment of Secondary Hyperparathyroidism: Results of a Phase 2 Trial Evaluating an Intravenous Peptide Agonist of the Calcium-Sensing Receptor.
abstract: OBJECTIVE
  This study evaluated the efficacy and safety of AMG416 (etelcalcitide), a novel peptide agonist of the calcium (Ca)-sensing receptor given intravenously (IV) after each hemodialysis session for the treatment of secondary hyperparathyroidism (SHPT).
  
  
  METHODS
  Adult subjects with SHPT on hemodialysis enrolled in a 12-week, dose titration (parent) study followed by an open-label extension phase. AMG416 was administered IV, thrice weekly starting at 5 mg/session and titrated based on the subject's parathyroid hormone (PTH) and albumin-corrected Ca (cCa) to target a PTH of 150-300 pg/ml. Efficacy (percent PTH change from baseline to the efficacy analysis period during the parent study) and safety (open-label extension phase) endpoints were evaluated.
  
  
  RESULTS
  Baseline (n = 37) mean (standard error [SE]) PTH was 853 (106 pg/ml). The mean (95% CI) percent change from baseline to the efficacy analysis period in PTH concentration was -53.6% (-60.8, -46.4). The proportion of subjects with ≥30% reduction in PTH from baseline to the efficacy assessment period (EAP) was 89% (32/36; 95% CI 73.9, 96.9). Results by the baseline PTH subgroup (≤700 vs. >700 pg/ml) were comparable for both analyses. The proportion of subjects achieving a PTH ≤300 pg/ml was 56% (n = 20/36) at the efficacy assessment period. The mean (SE) percent changes from baseline to EAP were observed for cCa -15% (1.0%) and phosphorus -10% (3.3%). Adverse events were mild to moderate in severity. The PTH reductions achieved in the parent study were maintained in the open-label extension phase.
  
  
  CONCLUSIONS
  AMG416 was well tolerated and appears to be an effective agent for the treatment of SHPT in patients on hemodialysis.
authors.affiliation: University of Rochester School of Medicine, Rochester, N.Y., USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bushinsky
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Martin
authors.forename: Gregory
authors.initials: G
authors.lastname: Bell
authors.forename: Saling
authors.initials: S
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: David M
authors.initials: DM
authors.lastname: Spiegel
authors.forename: Liron
authors.initials: L
authors.lastname: Walsh
authors.forename: T Christian
authors.initials: TC
authors.lastname: Mix
authors.forename: Reshma
authors.initials: R
authors.lastname: Kewalramani
mesh_terms: D061605:Administration, Intravenous; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D044169:Receptors, Calcium-Sensing / Q000819:agonists*; D006435:Renal Dialysis
chemical_list: D010455:Peptides; D044169:Receptors, Calcium-Sensing; C583569:etelcalcetide hydrochloride