A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Participants With CKD Not Receiving Dialysis
Received 13 February 2008; accepted 9 September 2008. published online 25 December 2008.
Refers to article:
Is It Worth Correcting Hyperparathyroidism if Hyperphosphatemia and Hypocalcemia Worsen? A Cinacalcet Story
Kamyar Kalantar-Zadeh, Csaba P. Kovesdy
American Journal of Kidney Diseases
February 2009 (Vol. 53, Issue 2, Pages 183-188) Full Text |
Full-Text PDF (123 KB)
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.
Address correspondence to Michel Chonchol, MD, Associate Professor, University of Colorado Health Sciences Center, Division of Renal Diseases and Hypertension, 4200 E. 9th Ave, Box C-281, Denver, CO 80262
A list of author affiliations appears at the end of this article.
ABSTRACT