title: A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis.
abstract: 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.
  
  
  METHODS
  Double-blind, randomized, 32-week, phase 3 study.
  
  
  METHODS
  404 participants with stage 3 or 4 CKD from 73 centers in 9 countries.
  
  
  METHODS
  Cinacalcet:placebo (3:1 ratio).
  
  
  METHODS
  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 mg(2)/dL(2) (+18.9%) and 38.9 +/- 6.9 mg(2)/dL(2) (+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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Colorado Health Science Center, Division of Renal Diseases and Hypertension, Denver, CO 80262, USA. michel.chonchol@uchsc.edu
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Abboud
authors.forename: Chaim
authors.initials: C
authors.lastname: Charytan
authors.forename: Angel L M
authors.initials: AL
authors.lastname: de Francisco
authors.forename: Shivinder
authors.initials: S
authors.lastname: Jolly
authors.forename: Mark
authors.initials: M
authors.lastname: Kaplan
authors.forename: Simon D
authors.initials: SD
authors.lastname: Roger
authors.forename: Shyamal
authors.initials: S
authors.lastname: Sarkar
authors.forename: Moetaz B
authors.initials: MB
authors.lastname: Albizem
authors.forename: T Christian H
authors.initials: TC
authors.lastname: Mix
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kubo
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
mesh_terms: D000368:Aged; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis
chemical_list: D009281:Naphthalenes; D010281:Parathyroid Hormone; D010758:Phosphorus; D002118:Calcium; D000069449:Cinacalcet