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

Two randomized clinical trials

Geoffrey A. Block, David A. Bushinsky, John Cunningham, Tilman B. Drueke, Markus Ketteler, Reshma Kewalramani, Kevin J. Martin, T. Christian Mix, Sharon Moe, Uptal D. Patel, Justin Silver, David M. Spiegel, Lulu Sterling, Liron Walsh, Glenn M. Chertow

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

IMPORTANCE Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease. OBJECTIVE To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis. DESIGN, SETTING, AND PARTICIPANTS 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, toMay 12, 2014. INTERVENTIONS Intravenous administration of etelcalcetide (n = 503) or placebo (n = 513) after each hemodialysis session for 26 weeks. MAIN OUTCOMES AND MEASURES The primary efficacy end pointwas 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. RESULTS The mean age of the 1023 patientswas 58.2 (SD, 14.4) years and 60.4%were men. Mean PTH concentrations at baseline and duringweeks 20-27were 849 and 384 pg/mL vs 820 and 897 pg/mLin the etelcalcetide and placebo groups, respectively, in trial A; corresponding valueswere 845 and 363 pg/mL vs 852 and 960pg/mLin trial B. Patients randomized to etelcalcetidewere significantly more likely to achieve the primary efficacy end point: In trialA, 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 etelcalcetidewere significantly more likely to achieve a PTH level of300pg/mL or lower: In trialA, 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 trialsAand 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%). CONCLUSIONS AND RELEVANCE 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.

Original languageEnglish (US)
Pages (from-to)146-155
Number of pages10
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
Placebos
Serum
Russia
Spasm
Israel
Chronic Renal Insufficiency
Intravenous Administration
Nausea
Canada
Vomiting
Safety

ASJC Scopus subject areas

  • Medicine(all)

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Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism : Two randomized clinical trials. / Block, Geoffrey A.; Bushinsky, David A.; Cunningham, John; Drueke, Tilman B.; Ketteler, Markus; Kewalramani, Reshma; Martin, Kevin J.; Mix, T. Christian; Moe, Sharon; Patel, Uptal D.; Silver, Justin; Spiegel, David M.; Sterling, Lulu; Walsh, Liron; Chertow, Glenn M.

In: JAMA - Journal of the American Medical Association, Vol. 317, No. 2, 10.01.2017, p. 146-155.

Research output: Contribution to journalArticle

Block, GA, Bushinsky, DA, Cunningham, J, Drueke, TB, Ketteler, M, Kewalramani, R, Martin, KJ, Mix, TC, Moe, S, Patel, UD, Silver, J, Spiegel, DM, Sterling, L, Walsh, L & Chertow, GM 2017, 'Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: Two randomized clinical trials', JAMA - Journal of the American Medical Association, vol. 317, no. 2, pp. 146-155. https://doi.org/10.1001/jama.2016.19456
Block, Geoffrey A. ; Bushinsky, David A. ; Cunningham, John ; Drueke, Tilman B. ; Ketteler, Markus ; Kewalramani, Reshma ; Martin, Kevin J. ; Mix, T. Christian ; Moe, Sharon ; Patel, Uptal D. ; Silver, Justin ; Spiegel, David M. ; Sterling, Lulu ; Walsh, Liron ; Chertow, Glenn M. / Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism : Two randomized clinical trials. In: JAMA - Journal of the American Medical Association. 2017 ; Vol. 317, No. 2. pp. 146-155.
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abstract = "IMPORTANCE Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease. OBJECTIVE To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis. DESIGN, SETTING, AND PARTICIPANTS 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, toMay 12, 2014. INTERVENTIONS Intravenous administration of etelcalcetide (n = 503) or placebo (n = 513) after each hemodialysis session for 26 weeks. MAIN OUTCOMES AND MEASURES The primary efficacy end pointwas 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. RESULTS The mean age of the 1023 patientswas 58.2 (SD, 14.4) years and 60.4{\%}were men. Mean PTH concentrations at baseline and duringweeks 20-27were 849 and 384 pg/mL vs 820 and 897 pg/mLin the etelcalcetide and placebo groups, respectively, in trial A; corresponding valueswere 845 and 363 pg/mL vs 852 and 960pg/mLin trial B. Patients randomized to etelcalcetidewere significantly more likely to achieve the primary efficacy end point: In trialA, 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 etelcalcetidewere significantly more likely to achieve a PTH level of300pg/mL or lower: In trialA, 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 trialsAand 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{\%}). CONCLUSIONS AND RELEVANCE 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.",
author = "Block, {Geoffrey A.} and Bushinsky, {David A.} and John Cunningham and Drueke, {Tilman B.} and Markus Ketteler and Reshma Kewalramani and Martin, {Kevin J.} and Mix, {T. Christian} and Sharon Moe and Patel, {Uptal D.} and Justin Silver and Spiegel, {David M.} and Lulu Sterling and Liron Walsh and Chertow, {Glenn M.}",
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T1 - Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism

T2 - Two randomized clinical trials

AU - Block, Geoffrey A.

AU - Bushinsky, David A.

AU - Cunningham, John

AU - Drueke, Tilman B.

AU - Ketteler, Markus

AU - Kewalramani, Reshma

AU - Martin, Kevin J.

AU - Mix, T. Christian

AU - Moe, Sharon

AU - Patel, Uptal D.

AU - Silver, Justin

AU - Spiegel, David M.

AU - Sterling, Lulu

AU - Walsh, Liron

AU - Chertow, Glenn M.

PY - 2017/1/10

Y1 - 2017/1/10

N2 - IMPORTANCE Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease. OBJECTIVE To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis. DESIGN, SETTING, AND PARTICIPANTS 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, toMay 12, 2014. INTERVENTIONS Intravenous administration of etelcalcetide (n = 503) or placebo (n = 513) after each hemodialysis session for 26 weeks. MAIN OUTCOMES AND MEASURES The primary efficacy end pointwas 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. RESULTS The mean age of the 1023 patientswas 58.2 (SD, 14.4) years and 60.4%were men. Mean PTH concentrations at baseline and duringweeks 20-27were 849 and 384 pg/mL vs 820 and 897 pg/mLin the etelcalcetide and placebo groups, respectively, in trial A; corresponding valueswere 845 and 363 pg/mL vs 852 and 960pg/mLin trial B. Patients randomized to etelcalcetidewere significantly more likely to achieve the primary efficacy end point: In trialA, 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 etelcalcetidewere significantly more likely to achieve a PTH level of300pg/mL or lower: In trialA, 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 trialsAand 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%). CONCLUSIONS AND RELEVANCE 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.

AB - IMPORTANCE Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease. OBJECTIVE To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis. DESIGN, SETTING, AND PARTICIPANTS 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, toMay 12, 2014. INTERVENTIONS Intravenous administration of etelcalcetide (n = 503) or placebo (n = 513) after each hemodialysis session for 26 weeks. MAIN OUTCOMES AND MEASURES The primary efficacy end pointwas 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. RESULTS The mean age of the 1023 patientswas 58.2 (SD, 14.4) years and 60.4%were men. Mean PTH concentrations at baseline and duringweeks 20-27were 849 and 384 pg/mL vs 820 and 897 pg/mLin the etelcalcetide and placebo groups, respectively, in trial A; corresponding valueswere 845 and 363 pg/mL vs 852 and 960pg/mLin trial B. Patients randomized to etelcalcetidewere significantly more likely to achieve the primary efficacy end point: In trialA, 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 etelcalcetidewere significantly more likely to achieve a PTH level of300pg/mL or lower: In trialA, 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 trialsAand 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%). CONCLUSIONS AND RELEVANCE 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.

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