Pharmacokinetics of eldecalcitol in primary osteoporosis patients - Randomized, double-blind, multicentre, long-term phase III clinical study

Background: Eldecalcitol, which was developed by Chugai Pharmaceutical Co., Ltd. (Tokyo, Japan) as a treatment for osteoporosis, is a new derivative of active vitamin D₃(1,25 (OH)₂D₃) with a hydroxypropyloxy group introduced at the 2β position. A Phase III, alfacalcidol-controlled clinical study of eldecalcitol was conducted in primary osteoporosis patients, with the incidence of new, non-traumatic vertebral fractures designated as the primary endpoint. Objectives: The objective of this study was to characterize the pharmacokinetic profile of eldecalcitol, using data obtained from this Phase III clinical study in primary osteoporosis patients. Methods: Patients were randomly assigned to an oral eldecalcitol or alfacalcidol group. Patients in the eldecalcitol group took one capsule each of eldecalcitol 0.75 μg and alfacalcidol placebo, while those in the alfacalcidol group took one capsule each of eldecalcitol placebo and alfacalcidol 1.0 μg, once daily for 144 weeks. Efficacy and safety in patients on eldecalcitol were compared with those in patients on alfacalcidol. For the pharmacokinetic analysis, the serum eldecalcitol concentration was measured at 48, 72, 96 and 144 weeks. Results: In the eldecalcitol group, the mean trough serum eldecalcitol concentrations obtained from patients without dose reduction at the time of blood collection were 286.9, 320.1, 387.3 and 344.0 pg/mL at 48, 72, 96 and 144 weeks, respectively. At all times, the trough serum eldecalcitol concentration remained within the range of values at 72 weeks. It was concluded from these results that the serum eldecalcitol concentration had reached steady state by 48 weeks. Calculation of the trough serum eldecalcitol concentration by baseline characteristic showed that the concentration was in a similar range in all categories of age, renal function and vitamin D supplementation. Conclusions: The trough serum eldecalcitol concentration in patients receiving eldecalcitol 0.75 μg did not change substantially from 48 to 144 weeks after starting treatment, suggesting that the pharmacokinetics of eldecalcitol do not vary with long-term treatment. Analysis using trough serum eldecalcitol concentrations revealed that age, renal function and vitamin D supplementation had no substantial effect on pharmacokinetics.