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Effects of Calcium Carbonate, Sevelamer Hydrochloride or Pantoprazole on the Pharmacokinetics of Cinacalcet

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Abstract

Background and Objectives

Secondary hyperparathyroidism is a common consequence of chronic kidney disease. Cinacalcet (Sensipar®) is often prescribed in combination to reduce elevated levels of parathyroid hormone, calcium and phosphorus. The objective of this study was to assess the effects of concomitantly administered therapies of calcium carbonate (CaCO3; TUMS®), sevelamer hydrochloride (HCl; Renagel®) and pantoprazole sodium (Protonix®) on the pharmacokinetics and safety of cinacalcet in healthy subjects.

Methods

Three randomized, open-label, two-way crossover pharmacokinetic studies were conducted in healthy subjects. Participants received single doses of cinacalcet alone or in combination with either CaCO3, sevelamer HCl or pantoprazole. The pharmacokinetic profile of cinacalcet was characterized. Safety assessments including adverse event reporting, changes in vital signs and clinical laboratory measurements were conducted throughout the studies.

Results

The 90 % confidence intervals for the area under the concentration–time curve from time zero to the last quantifiable concentration (AUClast), area under the concentration–time curve from time zero to infinity (AUC0–∞) and maximum plasma concentration (C max) of cinacalcet were within the accepted range of 80–125 % for both CaCO3 and sevelamer HCl co-administration with cinacalcet. No severe or serious adverse events or clinically relevant changes in physical or laboratory findings occurred during the studies.

Conclusion

The pharmacokinetic parameters of cinacalcet were not affected by co-administration of CaCO3, sevelamer HCl or pantoprazole. Co-administration of these agents with cinacalcet does not require an adjustment of the dose of cinacalcet.

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Acknowledgments

These studies were supported by Amgen Inc. The CaCO3 study was conducted by the MDS Harris Clinical Laboratory, Lincoln, NE, USA. The sevelamer HCl study was conducted by DaVita Clinical Research, Minneapolis, MS, USA, with analysis of pharmacokinetic and clinical samples by MDS Pharma Services, Lincoln, NE, USA, and Medtox Laboratories, Inc., Saint Paul, MN, USA, respectively, and data management provided by Clinimetrics, Inc. The pantoprazole study was conducted by MDS Pharma Services with data management provided by Clinimetrics, Inc. Statistical analysis was conducted by Amgen Inc. We thank Helen Gauton and Tom Westgate of Gardiner-Caldwell for providing editing support funded by Amgen. Holly Tomlin (employee and stockholder, Amgen Inc.) was responsible for editing and formatting the manuscript for the journal).

Conflict of Interest Statement

Desmond Padhi, Robert Harris and John T. Sullivan are employees and stockholders of Amgen Inc.

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Authors and Affiliations

  1. Early Development, Department of Medical Sciences, Amgen Inc., One Amgen Center Dr., Thousand Oaks, CA, 91320, USA

    Desmond Padhi

  2. Global Regulatory Affairs and Safety, Amgen Inc., Thousand Oaks, CA, USA

    Robert Harris & John T. Sullivan

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  1. Desmond Padhi
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  2. Robert Harris
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Correspondence to Desmond Padhi.

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Padhi, D., Harris, R. & Sullivan, J.T. Effects of Calcium Carbonate, Sevelamer Hydrochloride or Pantoprazole on the Pharmacokinetics of Cinacalcet. Clin Drug Investig 34, 537–544 (2014). https://doi.org/10.1007/s40261-014-0206-1

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