title: A randomized, double-blind, phase 2 study evaluating the safety and efficacy of AMG 416 for the treatment of secondary hyperparathyroidism in hemodialysis patients.
abstract: OBJECTIVE
  Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease. We evaluated AMG 416, a long-acting peptide agonist of the calcium-sensing receptor, to assess its safety, tolerability, and efficacy and to determine a safe and effective starting dose for subsequent phase 2 studies. The study was not designed to titrate AMG 416 dosing to achieve a specific PTH treatment goal.
  
  
  METHODS
  This is a multicenter, double-blind, randomized, placebo-controlled, dose-escalation study designed to evaluate the safety and efficacy of AMG 416 administered thrice weekly by IV bolus at the end of hemodialysis for up to 4 weeks. Eligible subjects were enrolled in one of three cohorts and treated with 5 mg of AMG 416 or placebo for 2 weeks (Cohort 1) or 5 or 10 mg of AMG 416 or placebo for 4 weeks (Cohorts 2 and 3). The primary endpoint was mean percentage change from baseline in PTH during the efficacy assessment phase (EAP) in Cohorts 2 and 3.
  
  
  RESULTS
  Analysis of the primary endpoint showed that treatment with AMG 416 at 10 mg (Cohort 2) and 5 mg (Cohort 3) for up to 4 weeks resulted in mean 49.4% and 33.0% reductions from baseline in PTH during the efficacy assessment phase, respectively (p < 0.05 for both cohorts compared to placebo group within the cohort). A substantial proportion of subjects treated with AMG 416 achieved PTH ≤300 pg/mL and ≥30% reduction in PTH from baseline in both cohorts. The observed decreases in serum-corrected calcium were well tolerated and serum phosphate levels also tended to decrease.
  
  
  CONCLUSIONS
  The present clinical findings support the continued development of AMG 416 as a treatment for SHPT in hemodialysis patients.
authors: Amgen , Thousand Oaks, CA , USA.
authors: Gregory
authors: G
authors: Bell
authors: Saling
authors: S
authors: Huang
authors: Kevin J
authors: KJ
authors: Martin
authors: Geoffrey A
authors: GA
authors: Block
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D044169:Receptors, Calcium-Sensing / Q000819:agonists*; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods; D051436:Renal Insufficiency, Chronic / Q000150:complications
chemical_list: D010281:Parathyroid Hormone; D010455:Peptides; D044169:Receptors, Calcium-Sensing; C583569:etelcalcetide hydrochloride
keywords: AMG 416; Calcium-sensing receptor; Chronic kidney disease; Hemodialysis; Secondary hyperparathyroidism