title: Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: Two Randomized Clinical Trials.
abstract: Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease.
  
  
  
  To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis.
  
  
  
  Two parallel, phase 3, randomized, placebo-controlled treatment trials were conducted in 1023 patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism. Trial A was conducted in 508 patients at 111 sites in the United States, Canada, Europe, Israel, Russia, and Australia from March 12, 2013, to June 12, 2014; trial B was conducted in 515 patients at 97 sites in the same countries from March 12, 2013, to May 12, 2014.
  
  
  
  Intravenous administration of etelcalcetide (n = 503) or placebo (n = 513) after each hemodialysis session for 26 weeks.
  
  
  
  The primary efficacy end point was the proportion of patients achieving greater than 30% reduction from baseline in mean PTH during weeks 20-27. A secondary efficacy end point was the proportion of patients achieving mean PTH of 300 pg/mL or lower.
  
  
  
  The mean age of the 1023 patients was 58.2 (SD, 14.4) years and 60.4% were men. Mean PTH concentrations at baseline and during weeks 20-27 were 849 and 384 pg/mL vs 820 and 897 pg/mL in the etelcalcetide and placebo groups, respectively, in trial A; corresponding values were 845 and 363 pg/mL vs 852 and 960 pg/mL in trial B. Patients randomized to etelcalcetide were significantly more likely to achieve the primary efficacy end point: in trial A, 188 of 254 (74.0%) vs 21 of 254 (8.3%; P < .001), for a difference in proportions of 65.7% (95% CI, 59.4%-72.1%) and in trial B, 192 of 255 (75.3%) vs 25 of 260 (9.6%; P < .001), for a difference in proportions of 65.7% (95% CI, 59.3%-72.1%). Patients randomized to etelcalcetide were significantly more likely to achieve a PTH level of 300 pg/mL or lower: in trial A, 126 of 254 (49.6%) vs 13 of 254 (5.1%; P < .001), for a difference in proportions of 44.5% (95% CI, 37.8%-51.2%) and in trial B, 136 of 255 (53.3%) vs 12 of 260 (4.6%; P < .001), for a difference in proportions of 48.7% (95% CI, 42.1%-55.4%). In trials A and B, respectively, patients receiving etelcalcetide had more muscle spasms (12.0% and 11.1% vs 7.1% and 6.2% with placebo), nausea (12.4% and 9.1% vs 5.1% and 7.3%), and vomiting (10.4% and 7.5% vs 7.1% and 3.1%).
  
  
  
  Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, use of etelcalcetide compared with placebo resulted in greater reduction in serum PTH over 26 weeks. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.
  
  
  
  clinicaltrials.gov Identifiers: NCT01788046.
authors.affiliation: Denver Nephrology, Denver, Colorado.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.affiliation: University of Rochester, Rochester, New York.
authors.forename: David A
authors.initials: DA
authors.lastname: Bushinsky
authors.affiliation: University College London, London, England.
authors.forename: John
authors.initials: J
authors.lastname: Cunningham
authors.affiliation: Inserm, Université de Picardie, Amiens, France.
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drueke
authors.affiliation: Klinikum Coburg-GmbH, Coburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Ketteler
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Reshma
authors.initials: R
authors.lastname: Kewalramani
authors.affiliation: Saint Louis University, St Louis, Missouri.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Martin
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: T Christian
authors.initials: TC
authors.lastname: Mix
authors.affiliation: Indiana University, Indianapolis.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Uptal D
authors.initials: UD
authors.lastname: Patel
authors.affiliation: Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Justin
authors.initials: J
authors.lastname: Silver
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: David M
authors.initials: DM
authors.lastname: Spiegel
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Lulu
authors.initials: L
authors.lastname: Sterling
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Liron
authors.initials: L
authors.lastname: Walsh
authors.affiliation: Stanford University, Stanford, California.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
mesh_terms: D057966:Calcimimetic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015990:Placebo Effect; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000150:complications; D013997:Time Factors
chemical_list: D057966:Calcimimetic Agents; D010281:Parathyroid Hormone; D010455:Peptides; D005346:Fibroblast Growth Factors; C583569:etelcalcetide hydrochloride; D000089703:Fibroblast Growth Factor-23; D002118:Calcium