19-NOR-1-ALPHA-25-DIHYDROXYVITAMIN D-2 (PARICALCITOL) SAFELY AND EFFECTIVELY REDUCES THE LEVELS OF INTACT PARATHYROID-HORMONE IN PATIENTS ON HEMODIALYSIS

Paricalcitol (19-nor-1 alpha-25-dihydroxyvitamin D-2), a new vitamin D analog developed for the treatment of secondary hyperparathyroidism, was evaluated in three double-blind, placebo-controlled, dose-escalati ng, randomized multicenter trials. A total of 78 patients (40 Paricalc itol injection, 38 placebo) achieved treatment phase eligibility, whic h included intact parathyroid hormone (iPTH) greater than or equal to 400 pg/ml, normalized serum calcium levels between 8.0 and 10.0 mg/dl, and calcium x phosphorus product values less than 75. Study end point s included a decrease in iPTH of at least 30% or a maximum of five dos e escalations. After a 4-wk washout, paricalcitol or placebo was admin istered intravenously three times per week after dialysis for 12 wk. S tudy drug was started at a dose of 0.04 mu g/kg and was increased by 0 .04 mu g/kg every 2 wk to a maximal allowable dose of 0.24 mu g/kg or until at least a 30% decrease in serum iPTH was achieved. The dose of paricalcitol that decreased iPTH by at least 30% became the maintenanc e dose. Of 40 patients receiving paricalcitol, 27 (68%) had at least a 30% decrease in serum iPTH for 4 consecutive weeks, compared with thr ee of 38 patients (8%) receiving placebo (P < 0.001). For patients who received 12 wk of treatment with paricalcitol, the levels of iPTH dec reased significantly from 795 +/- 86 to 406 +/- 106 pg/ml (P < 0.001), whereas the values for PTH were 679 +/- 41 pg/ml before and 592 +/- 4 1 pg/ml after 12 wk of therapy in patients receiving placebo (P = NS). Also, there was a significant difference between treatment groups for the change from baseline PTH levels (P < 0,001). Paricalcitol treatme nt resulted in a significant reduction in serum alkaline phosphatase f rom 148 +/- 23 U/L to 101 +/- 14 U/L (P < 0.001) in patients treated f or 12 wk compared with 120 +/- 9 U/L to 130 +/- 11 U/L (P = NS) in pat ients receiving placebo for 12 wk, Importantly, hypercalcemia did not occur before achieving target serum iPTH levels in any of the paricalc itol-treated patients. There was no significant difference for the cha nge from baseline in serum phosphorus within or between treatment grou ps. There was no significant difference in adverse events between the paricalcitol and placebo-treated groups. These studies demonstrate tha t paricalcitol safely and effectively suppresses iPTH levels in hemodi alysis patients. This second generation vitamin D analog may have a wi der therapeutic window than current vitamin D preparations, and thus m ay allow reduction in PTH with less hypercalcemia.