학술논문
A randomized, controlled, three-arm, open-label, cross-over bioequivalence study comparing calcium acetate oral solution and calcium acetate gelcaps in healthy volunteers
Document Type
Academic Journal
Author
Source
Journal of Applied Research. June 1, 2012, Vol. 12 Issue 2, p98, 10 p.
Subject
Language
English
ISSN
1537-064X
Abstract
Hyperphosphatemia in end-stage renal disease (ESRD) is due to the inability of the damaged kidneys to eliminate phosphate. In hemodialysis patients, hyperphosphatemia is a major cause of morbidity and mortality, [...]
Background/Aim: Hemodialysis (HD) alone does not adequately control serum phosphorus levels. Hyperphosphatemia in end-stage renal disease is treated by a combination of dietary phosphate restriction and administration of phosphate binders. However, the daily pill burden from phosphate binders has been linked to non-adherence, poor serum phosphorus control, and lower quality of life. A novel formulation of calcium acetate oral solution (Phoslyra™) has been developed to address these clinical challenges. This study was conducted to demonstrate bioequivalence between Phoslyra and PhosLo® Gelcaps (calcium acetate gelcaps). Methods: A controlled, 3-arm, open label, cross-over study included 46 healthy subjects on a controlled diet randomized into three treatment sequences to receive Phoslyra, PhosLo Gelcaps, or calcium citrate (positive control) with a 5-10 day washout period. Serum phosphorus,(P) calcium,(Ca) glucose, insulin, and 24 hr urine were measured at baseline and at the end of each 3-day treatment period. The primary objective was to demonstrate the bioequivalence of calcium acetate oral solution to calcium acetate gelcaps with respect to serum phosphorus and urinary calcium excretion. Secondary objectives were to compare changes in urinary phosphorus, serum calcium, serum glucose, and insulin levels. Results: Thirty-six subjects completed the study. Calcium acetate oral solution was bioequivalent to calcium acetate gelcaps based on the 90% CIs of the serum phosphorus ratios for Cmax (peak concentration) and AUC0-6 (area under the curve from time 0-6 hrs). Urinary calcium level with the calcium acetate oral solution was not more than the level with the calcium acetate gelcaps based on the 90% CIs for Rmax (maximal rate of urinary excretion) and Ae0-6 (cumulative urinary excretion from 0-6 hours). Serum glucose and insulin levels did not indicate any effect of maltitol in the liquid formulation on serum glucose control. Cmax, and average glucose concentration during the 6-hour sampling interval remained within the strict bioequivalence criteria. Conclusion: Calcium acetate oral solution was well tolerated with a pharmacodynamic and pharmacokinetic profile equivalent to calcium acetate gelcaps. (ClinicalTrials.gov NCT00742820) BACKGROUND) KEY WORDS: Phosphate binders, calcium acetate oral solution, bioequivalence, serum phosphorus, serum calcium, urine calcium, mineral metabolism.
Background/Aim: Hemodialysis (HD) alone does not adequately control serum phosphorus levels. Hyperphosphatemia in end-stage renal disease is treated by a combination of dietary phosphate restriction and administration of phosphate binders. However, the daily pill burden from phosphate binders has been linked to non-adherence, poor serum phosphorus control, and lower quality of life. A novel formulation of calcium acetate oral solution (Phoslyra™) has been developed to address these clinical challenges. This study was conducted to demonstrate bioequivalence between Phoslyra and PhosLo® Gelcaps (calcium acetate gelcaps). Methods: A controlled, 3-arm, open label, cross-over study included 46 healthy subjects on a controlled diet randomized into three treatment sequences to receive Phoslyra, PhosLo Gelcaps, or calcium citrate (positive control) with a 5-10 day washout period. Serum phosphorus,(P) calcium,(Ca) glucose, insulin, and 24 hr urine were measured at baseline and at the end of each 3-day treatment period. The primary objective was to demonstrate the bioequivalence of calcium acetate oral solution to calcium acetate gelcaps with respect to serum phosphorus and urinary calcium excretion. Secondary objectives were to compare changes in urinary phosphorus, serum calcium, serum glucose, and insulin levels. Results: Thirty-six subjects completed the study. Calcium acetate oral solution was bioequivalent to calcium acetate gelcaps based on the 90% CIs of the serum phosphorus ratios for Cmax (peak concentration) and AUC0-6 (area under the curve from time 0-6 hrs). Urinary calcium level with the calcium acetate oral solution was not more than the level with the calcium acetate gelcaps based on the 90% CIs for Rmax (maximal rate of urinary excretion) and Ae0-6 (cumulative urinary excretion from 0-6 hours). Serum glucose and insulin levels did not indicate any effect of maltitol in the liquid formulation on serum glucose control. Cmax, and average glucose concentration during the 6-hour sampling interval remained within the strict bioequivalence criteria. Conclusion: Calcium acetate oral solution was well tolerated with a pharmacodynamic and pharmacokinetic profile equivalent to calcium acetate gelcaps. (ClinicalTrials.gov NCT00742820) BACKGROUND) KEY WORDS: Phosphate binders, calcium acetate oral solution, bioequivalence, serum phosphorus, serum calcium, urine calcium, mineral metabolism.