Pharmacokinetics of Eldecalcitol in Primary Osteoporosis Patients -Randomized, Double-Blind, Multicentre, Long-Term Phase SI Clinical Study

摘要

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 2卩position. A Phase HI, 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 HI 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 jug and alfacalcidol placebo, while those in the alfacalcidol group took one capsule each of eldecalcitol placebo and alfacalcidol1.0 /ug, once daily for144 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 and144 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 peg did not change substantially from 48 to144 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.