14 CLINICAL STUDIES
The safety and efficacy of Paricalcitol Injection have been established based on adult studies of another paricalcitol injection product in patients with CKD on hemodialysis. Below is a display of the results of these studies of paricalcitol injection.
Adult Studies in CKD on Dialysis
Three 12-week, placebo-controlled studies were conducted with paricalcitol injection in 78 patients with chronic kidney disease on dialysis. In these studies, patients ranged in age from 22 to 90 years, 51% were males, 13% were Caucasian, 79% were African-American, and 8% were Hispanic. The most common causes of renal failure were hypertension and diabetes. The dose of paricalcitol injection was started at 0.04 mcg/kg 3 times per week intravenously. The dose was increased by 0.04 mcg/kg every 2 weeks until intact PTH levels were decreased at least 30% from baseline or a fifth escalation brought the dose to 0.24 mcg/kg, or intact PTH fell to less than 100 pg/mL, or the Ca × P product was greater than 75 within any 2 week period, or serum calcium became greater than 11.5 mg/dL at any time.
Patients treated with paricalcitol injection achieved a mean intact PTH reduction of 30% within 6 weeks. The results from these studies are as follows:
| Group (No. of Pts.) | Baseline Mean (Range) | Mean (SE) Change From Baseline to Final Evaluation | |
|---|---|---|---|
| Intact PTH (pg/mL) | Paricalcitol injection (n=40) | 783 (291 – 2076) | -379 (43.7) |
| Placebo (n=38) | 745 (320 – 1671) | -69.6 (44.8) | |
| Alkaline Phosphatase (U/L) | Paricalcitol injection (n=31) | 150 (40 – 600) | -41.5 (10.6) |
| Placebo (n=34) | 169 (56 – 911) | +2.6 (10.1) | |
| Phosphorus (mg/dL) | Paricalcitol injection (n=40) | 5.8 (3.7 – 10.2) | +0.47 (0.3) |
| Placebo (n=38) | 6.0 (2.8 – 8.8) | -0.47 (0.3) | |
| Calcium × Phosphorus Product | Paricalcitol injection (n=40) | 54 (32 – 106) | +7.9 (2.2) |
| Placebo (n=38) | 54 (26 – 77) | -3.9 (2.3) | |
Pediatric Study in CKD on Dialysis
Paricalcitol injection was evaluated in a 12-week randomized, double-blind, placebo-controlled study of 29 pediatric patients, aged 5 to 19 years, with CKD on hemodialysis; nearly all had received some form of vitamin D prior to the study. Of the 29 patients, 76% were male, 52% were Caucasian and 45% were African-American. The initial dose of paricalcitol injection was 0.04 mcg/kg 3 times per week, based on baseline intact PTH level of less than 500 pg/mL, or 0.08 mcg/kg 3 times per week, based on baseline intact PTH level of 500 pg/mL or greater. The dose of paricalcitol injection was adjusted in 0.04 mcg/kg increments based on the levels of serum intact PTH, calcium and Ca × P. The mean baseline levels of intact PTH were 841 pg/mL for the 15 patients treated with paricalcitol injection and 740 pg/mL for the 14 placebo-treated patients. The mean dose of paricalcitol injection administered was 4.6 mcg (range: 0.8 mcg to 9.6 mcg). Sixty-seven percent of the patients treated with paricalcitol injection and 14% of the placebo-treated patients completed the trial. Seventy-one percent of the placebo-treated patients discontinued due to excessive elevations in intact PTH levels, as defined by 2 consecutive intact PTH levels greater than 700 pg/mL and greater than baseline after 4 weeks of treatment.
The primary efficacy analysis demonstrated that 60% of patients treated with paricalcitol injection and 21% of placebo-treated patients achieved two consecutive greater than or equal to 30% reductions from baseline in intact PTH.