TY - JOUR
T1 - A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Participants With CKD Not Receiving Dialysis
AU - Chonchol, Michel
AU - Locatelli, Francesco
AU - Abboud, Hanna E.
AU - Charytan, Chaim
AU - de Francisco, Angel L.M.
AU - Jolly, Shivinder
AU - Kaplan, Mark
AU - Roger, Simon D.
AU - Sarkar, Shyamal
AU - Albizem, Moetaz B.
AU - Mix, T. Christian H.
AU - Kubo, Yumi
AU - Block, Geoffrey A.
N1 - Funding Information:
Support: The writing of this manuscript was supported by Amgen Inc; see Financial Disclosure for further information.
Funding Information:
Financial Disclosure: This trial (20000178) was sponsored by Amgen Inc, which markets cinacalcet. Dr Chonchol is a member of advisory boards for Amgen; Dr Locatelli is a member of advisory boards for Amgen-Dompé, Shire, and Mitsubishi; Dr Charytan receives research and/or consultation support from Amgen; Dr de Francisco is a clinical advisor for Amgen and lectures for Amgen, Roche, Jansen Cilag, and Abbott; Dr Jolly is a stockholder of Amgen; Drs Albizem and Mix and Ms Kubo are employees of and stockholders of Amgen; and Dr Block is an advisor for Amgen and has received research support from Amgen.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/2
Y1 - 2009/2
N2 - Background: Secondary hyperparathyroidism is observed in patients with early chronic kidney disease (CKD). This study investigated the safety and efficacy of cinacalcet for secondary hyperparathyroidism in participants with CKD not receiving dialysis. Study Design: Double-blind, randomized, 32-week, phase 3 study. Setting & Participants: 404 participants with stage 3 or 4 CKD from 73 centers in 9 countries. Interventions: Cinacalcet:placebo (3:1 ratio). Outcomes & Measurements: Proportion of participants with a mean decrease of 30% or greater in intact parathyroid hormone (iPTH) level, proportion with iPTH level of 70 or less or 110 or less pg/mL (stage 3 and 4 CKD, respectively), and mean percentage of iPTH change from baseline, all during the efficacy-assessment phase. Results: A greater proportion of cinacalcet than placebo participants achieved a 30% or greater decrease in iPTH level (74% versus 28%; P < 0.001), corresponding to a 43.1% decrease in iPTH level from baseline (cinacalcet) compared with a 1.1% increase (placebo). At week 32, serum calcium levels were 8.9 ± 0.8 mg/dL (-8.9%; cinacalcet) and 9.9 ± 0.6 mg/dL (+0.8%; placebo), phosphorus levels were 4.5 ± 1.0 mg/dL (+21.4%) and 4.0 ± 0.7 mg/dL (+6.8%), and calcium-phosphorus product values were 40.1 ± 8.3 mg2/dL2 (+18.9%) and 38.9 ± 6.9 mg2/dL2 (+17.1%), respectively. During the study course, 62% (cinacalcet) and 1% (placebo) of participants experienced 2 consecutive serum calcium concentrations less than 8.4 mg/dL. They generally were asymptomatic and without significant clinical consequences. Treatment generally was well tolerated, and most adverse events were mild to moderate in severity. Limitations: The study was not designed to assess the effects of cinacalcet on vascular calcification, bone histomorphometric parameters, or other clinical outcomes. It is not known whether the observed differences in changes in iPTH levels are clinically more important than observed differences in changes in serum calcium or phosphorus levels or dosages of vitamin D sterols and phosphate binders. Conclusions: These data show that cinacalcet treatment in patients with CKD not receiving dialysis can decrease plasma iPTH levels, but with frequent (albeit generally asymptomatic) serum calcium levels less than 8.4 mg/dL and increases in serum phosphorus levels.
AB - Background: Secondary hyperparathyroidism is observed in patients with early chronic kidney disease (CKD). This study investigated the safety and efficacy of cinacalcet for secondary hyperparathyroidism in participants with CKD not receiving dialysis. Study Design: Double-blind, randomized, 32-week, phase 3 study. Setting & Participants: 404 participants with stage 3 or 4 CKD from 73 centers in 9 countries. Interventions: Cinacalcet:placebo (3:1 ratio). Outcomes & Measurements: Proportion of participants with a mean decrease of 30% or greater in intact parathyroid hormone (iPTH) level, proportion with iPTH level of 70 or less or 110 or less pg/mL (stage 3 and 4 CKD, respectively), and mean percentage of iPTH change from baseline, all during the efficacy-assessment phase. Results: A greater proportion of cinacalcet than placebo participants achieved a 30% or greater decrease in iPTH level (74% versus 28%; P < 0.001), corresponding to a 43.1% decrease in iPTH level from baseline (cinacalcet) compared with a 1.1% increase (placebo). At week 32, serum calcium levels were 8.9 ± 0.8 mg/dL (-8.9%; cinacalcet) and 9.9 ± 0.6 mg/dL (+0.8%; placebo), phosphorus levels were 4.5 ± 1.0 mg/dL (+21.4%) and 4.0 ± 0.7 mg/dL (+6.8%), and calcium-phosphorus product values were 40.1 ± 8.3 mg2/dL2 (+18.9%) and 38.9 ± 6.9 mg2/dL2 (+17.1%), respectively. During the study course, 62% (cinacalcet) and 1% (placebo) of participants experienced 2 consecutive serum calcium concentrations less than 8.4 mg/dL. They generally were asymptomatic and without significant clinical consequences. Treatment generally was well tolerated, and most adverse events were mild to moderate in severity. Limitations: The study was not designed to assess the effects of cinacalcet on vascular calcification, bone histomorphometric parameters, or other clinical outcomes. It is not known whether the observed differences in changes in iPTH levels are clinically more important than observed differences in changes in serum calcium or phosphorus levels or dosages of vitamin D sterols and phosphate binders. Conclusions: These data show that cinacalcet treatment in patients with CKD not receiving dialysis can decrease plasma iPTH levels, but with frequent (albeit generally asymptomatic) serum calcium levels less than 8.4 mg/dL and increases in serum phosphorus levels.
KW - Calcimimetic
KW - chronic kidney disease
KW - secondary hyperparathyroidism
KW - stage 3
KW - stage 4
UR - http://www.scopus.com/inward/record.url?scp=58349117276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58349117276&partnerID=8YFLogxK
U2 - 10.1053/j.ajkd.2008.09.021
DO - 10.1053/j.ajkd.2008.09.021
M3 - Article
C2 - 19110359
AN - SCOPUS:58349117276
VL - 53
SP - 197
EP - 207
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 2
ER -