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A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis.
Am J Kidney Dis. 2009 Feb; 53(2):197-207.AJ

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.

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 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.

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.

Authors+Show Affiliations

University of Colorado Health Science Center, Division of Renal Diseases and Hypertension, Denver, CO 80262, USA. michel.chonchol@uchsc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19110359

Citation

Chonchol, Michel, et al. "A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Participants With CKD Not Receiving Dialysis." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 53, no. 2, 2009, pp. 197-207.
Chonchol M, Locatelli F, Abboud HE, et al. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis. Am J Kidney Dis. 2009;53(2):197-207.
Chonchol, M., Locatelli, F., Abboud, H. E., Charytan, C., de Francisco, A. L., Jolly, S., Kaplan, M., Roger, S. D., Sarkar, S., Albizem, M. B., Mix, T. C., Kubo, Y., & Block, G. A. (2009). A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 53(2), 197-207. https://doi.org/10.1053/j.ajkd.2008.09.021
Chonchol M, et al. A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Participants With CKD Not Receiving Dialysis. Am J Kidney Dis. 2009;53(2):197-207. PubMed PMID: 19110359.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2008/12/24/ PY - 2008/02/13/received PY - 2008/09/09/accepted PY - 2008/12/27/entrez PY - 2008/12/27/pubmed PY - 2009/2/12/medline SP - 197 EP - 207 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am. J. Kidney Dis. VL - 53 IS - 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 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. 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/19110359/A_randomized_double_blind_placebo_controlled_study_to_assess_the_efficacy_and_safety_of_cinacalcet_HCl_in_participants_with_CKD_not_receiving_dialysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(08)01569-2 DB - PRIME DP - Unbound Medicine ER -