Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism

A randomized clinical trial

Geoffrey A. Block, David A. Bushinsky, Sunfa Cheng, John Cunningham, Bastian Dehmel, Tilman B. Drueke, Markus Ketteler, Reshma Kewalramani, Kevin J. Martin, Sharon Moe, Uptal D. Patel, Justin Silver, Yan Sun, Hao Wang, Glenn M. Chertow

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

IMPORTANCE Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. OBJECTIVE To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 toMay 2014, with end of follow-up in January 2015. INTERVENTIONS Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily. MAIN OUTCOMES AND MEASURES The primary efficacy end pointwas noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting. RESULTS The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2%were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5%(95%CI, -17.5%to -3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) to randomized etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95%CI, 4.7%to 19.5%). The most common adverse effect was decreased blood calcium (68.9%vs 59.8%). CONCLUSIONS AND RELEVANCE Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.

Original languageEnglish (US)
Pages (from-to)156-164
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume317
Issue number2
DOIs
StatePublished - Jan 10 2017

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Secondary Hyperparathyroidism
Parathyroid Hormone
Renal Dialysis
Randomized Controlled Trials
Serum
Placebos
Safety
Cinacalcet Hydrochloride
Russia
New Zealand
Pharmaceutical Preparations
Nausea
Canada
Vomiting
Clinical Trials
Calcium
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism : A randomized clinical trial. / Block, Geoffrey A.; Bushinsky, David A.; Cheng, Sunfa; Cunningham, John; Dehmel, Bastian; Drueke, Tilman B.; Ketteler, Markus; Kewalramani, Reshma; Martin, Kevin J.; Moe, Sharon; Patel, Uptal D.; Silver, Justin; Sun, Yan; Wang, Hao; Chertow, Glenn M.

In: JAMA - Journal of the American Medical Association, Vol. 317, No. 2, 10.01.2017, p. 156-164.

Research output: Contribution to journalArticle

Block, GA, Bushinsky, DA, Cheng, S, Cunningham, J, Dehmel, B, Drueke, TB, Ketteler, M, Kewalramani, R, Martin, KJ, Moe, S, Patel, UD, Silver, J, Sun, Y, Wang, H & Chertow, GM 2017, 'Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: A randomized clinical trial', JAMA - Journal of the American Medical Association, vol. 317, no. 2, pp. 156-164. https://doi.org/10.1001/jama.2016.19468
Block, Geoffrey A. ; Bushinsky, David A. ; Cheng, Sunfa ; Cunningham, John ; Dehmel, Bastian ; Drueke, Tilman B. ; Ketteler, Markus ; Kewalramani, Reshma ; Martin, Kevin J. ; Moe, Sharon ; Patel, Uptal D. ; Silver, Justin ; Sun, Yan ; Wang, Hao ; Chertow, Glenn M. / Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism : A randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2017 ; Vol. 317, No. 2. pp. 156-164.
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T1 - Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism

T2 - A randomized clinical trial

AU - Block, Geoffrey A.

AU - Bushinsky, David A.

AU - Cheng, Sunfa

AU - Cunningham, John

AU - Dehmel, Bastian

AU - Drueke, Tilman B.

AU - Ketteler, Markus

AU - Kewalramani, Reshma

AU - Martin, Kevin J.

AU - Moe, Sharon

AU - Patel, Uptal D.

AU - Silver, Justin

AU - Sun, Yan

AU - Wang, Hao

AU - Chertow, Glenn M.

PY - 2017/1/10

Y1 - 2017/1/10

N2 - IMPORTANCE Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. OBJECTIVE To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 toMay 2014, with end of follow-up in January 2015. INTERVENTIONS Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily. MAIN OUTCOMES AND MEASURES The primary efficacy end pointwas noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting. RESULTS The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2%were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5%(95%CI, -17.5%to -3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) to randomized etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95%CI, 4.7%to 19.5%). The most common adverse effect was decreased blood calcium (68.9%vs 59.8%). CONCLUSIONS AND RELEVANCE Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.

AB - IMPORTANCE Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. OBJECTIVE To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 toMay 2014, with end of follow-up in January 2015. INTERVENTIONS Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily. MAIN OUTCOMES AND MEASURES The primary efficacy end pointwas noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting. RESULTS The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2%were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5%(95%CI, -17.5%to -3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) to randomized etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95%CI, 4.7%to 19.5%). The most common adverse effect was decreased blood calcium (68.9%vs 59.8%). CONCLUSIONS AND RELEVANCE Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.

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