A long-term, multicenter study of the efficacy and safety of paricalcitol in end-stage renal disease

Background: Paricalcitol is a vitamin D analog approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic rena l failure. This study was designed to evaluate the long-term efficacy and s afety of paricalcitol. Additional analysis evaluated the effects of parical citol in hypocalcemic and hyperphosphatemic subpopulations. Patients and me thods: One hundred sixty-four end-stage renal disease (ESRD) patiesnts on h emodialysis were treated in an open-label, multicenter study lasting up to 13 months in duration. After a baseline or washout period, an initial start ing dose of 0.04 - 0.393 mug/kg was given 2 - 3 times per week. This dose w as adjusted at the discretion of the investigator according to the patient' s intact parathyroid hormone level (iPTH), calcium level, and calciumphosph orus (Ca x P) product. The therapy was intended to reproduce expected clini cal use of paricalcitol. Patients represented a wide cross-section of the E SRD population, and were not excluded from the study based on age or underl ying disease. Results: The mean paricalcitol dose level throughout the Stud y was 0.10 mug/kg. The mean iPTH levels (baseline mean 628.3 +/- 27.65 pg/m l) decreased rapidly during the first 4 months of therapy, and reached the designated target range (100 - 300 pg/ml) by month 5 (mean 295.3 +/- 25.69 pg/ml), A maximum mean decrease in iPTH level of 409 +/- 35.01 pg/ml was se en at month 13. Throughout the course of the study, the mean normalized cal cium level was maintained well within the normal range (9.44 - 9.94 mg/dl). The mean phosphorus level was maintained in an acceptable range throughout the study (5.92 - 6.53 mg/dl). Mean Ca. x P product was maintained between 52 and 65. Mean alkaline phosphatase levels decreased significantly from b aseline with a maximum mean decrease of 62 +/- 17.3 U/1 observed at month 9 . In 34 initially hypocalcemic patients (mean of 7.7 mg/dl) iPTH levels dec reased from baseline, on average, by 443 +/- 81.86 pg/ml while mean calcium levels rose by 1.2 +/- 0.23 mg/dl to reach the normal range. In 35 initial ly hyperphosphatemic patients (mean of 8.0 mg/dl) iPTH levels decreased, on average, by 515 +/- 103.31 pg/ml with an associated mean decrease in phosp horus of 0.57 +/- 0.52 mg/dl. Adverse events that were considered by the in vestigator to have a possible, probable, or definite relationship to study drug occurred in 26% of patients. Other than expected temporary effects of hypercalcemia, and hyperphosphatemia, the only possible trends for causally -related adverse events were for nausea/vomiting and metallic taste. Conclu sions: This long-term study of paricalcitol demonstrates that it rapidly an d effectively suppresses iPTH levels in a wide spectrum of ESRD patients an d caused no unexpected adverse events.