Abstract
The dose dependency of falecalcitriol (ST-630), an analogue of the active vitamin D3, which has very strong biological activity, was investigated for treatment of secondary hyperparathyroidism in patients undergoing hemodialysis in a double-blind, multicenter study. The final global improvement rating was assessed by using the percent change in serum level of HS-PTH (44-68 midregion PTH) as an index. The rates of “improved” or better were 31% for the 0.05μg/day group, 38% for the 0.15μg/day group, and 59% for the 0.3μg/day group. The serum HS-PTH levels showed a significant increase (average increase 20%) in the 0.05μg/day group, and a tendency toward increase in the 0.15μg/day group, but a decrease (average reduction 10%) in the 0.3μg/day group, with a significant difference between the 0.05μg/day and 0.3μg/day groups. Falecalcitriol thus showed dose-dependent suppression in HS-PTH. C-PTH displayed the same changes as HS-PTH, and the decrease in C-PTH was statistically significantly more pronounced in the 0.3μg/day group. In overall safety rating, the unsafe rates (cases assessed as “almost safe” or less) were 2% in the 0.05μg/day group, 9% in the 0.15μg/day group, and 20% in the 0.3μg/day group. Major adverse reactions in the 0.3μg/day group were hypercalcemia (3 patients) and bradycardia with an abnormal feeling in the chest (1 patient). The highest level of serum calcium (albumin-adjusted value) among the patients with hypercalcemia was 12.3mg/dl, but in all three patients the level returned to normal within 20 days, and no particular problems were observed. The mean serum calcium levels in the 0.3μg/day group remained within the normal range throughout the treatment period, and there was no rise in mean serum phosphate concentration in any of the three groups. A serious adverse reaction involving hepatic dysfunction was noted in 1 patient of the 0.15μg/day group, but it improved when treatment was discontinued. As these findings show, falecalcitriol showed outstanding efficacy in the treatment of secondary hyperthyroidism in chronic renal failure. When efficacy and safety were taken into consideration, the optimal dose was assumed to be 0.3μg/day. However, hypercalcemia requires adequate attention, and monitoring of serum calcium levels at suitable intervals is considered important, in order to ensure safety. Further studies considered necessary, are an objective comparison of the optimal dose established in this study with a control drug; an investigation of efficacy and safety during long-term administration; and an investigation of the effect on bone lesions.
