Pediatric Use
The safety and effectiveness of Zemplar were examined in a 12-week randomized, double-blind, placebo-controlled study of 29 pediatric patients, aged 5-19 years, with end-stage renal disease on hemodialysis and nearly all had received some form of vitamin D prior to the study. Seventy-six percent of the patients were male, 52% were Caucasian and 45% were African-American. The initial dose of Zemplar was 0.04 mcg/kg 3 times per week based on baseline iPTH level of less than 500 pg/mL, or 0.08 mcg/kg 3 times a week, based on baseline iPTH level of ≥ 500 pg/mL, respectively. The dose of Zemplar was adjusted in 0.04 mcg/kg increments based on the levels of serum iPTH, calcium and Ca x P. The mean baseline levels of iPTH were 841 pg/mL for the 15 Zemplar-treated patients and 740 pg/mL for the 14 placebo-treated subjects. The mean dose of Zemplar administered was 4.6 mcg (range: 0.8 mcg – 9.6 mcg). Ten of the 15 (67%) Zemplar-treated patients and 2 of the 14 (14%) placebo-treated patients completed the trial. Ten of the placebo patients (71%) were discontinued due to excessive elevations in iPTH levels as defined by 2 consecutive iPTH levels > 700 pg/mL and greater than baseline after 4 weeks of treatment.

In the primary efficacy analysis, 9 of 15 (60%) subjects in the Zemplar group had 2 consecutive 30% decreases from baseline iPTH compared with 3 of 14 (21%) patients in the placebo group (95% CI for the difference between groups –1%, 63%). Twenty-three percent of Zemplar vs. 31% of placebo patients had at least one serum calcium level > 10.3 mg/dL, and 40% vs. 14% of Zemplar vs. placebo subjects had at least one Ca x P ion product > 72 (mg/dL)2. The overall percentage of serum calcium measurements > 10.3 mg/dL was 7% in the Zemplar group and 7% in the placebo group; the overall percentage of patients with Ca x P product > 72 (mg/dL)2 was 8% in the Zemplar group and 7% in the placebo group. No subjects in either the Zemplar group or placebo group developed hypercalcemia (defined as at least one calcium value > 11.2 mg/dL) during the study.

Geriatric Use
Of the 40 patients receiving Zemplar in the three phase 3 placebo-controlled CKD Stage 5 studies, 10 patients were 65 years or over. In these studies, no overall differences in efficacy or safety were observed between patients 65 years or older and younger patients.

ADVERSE REACTIONS
Zemplar has been eva luated for safety in clinical studies in 609 CKD Stage 5 patients. In four, placebo-controlled, double-blind, multicenter studies, discontinuation of therapy due to any adverse event occurred in 6.5% of 62 patients treated with Zemplar (dosage titrated as tolerated, see CLINICAL PHARMACOLOGY - Clinical Studies) and 2.0% of 51 patients treated with placebo for 1 to 3 months. Adverse events occurring in the Zemplar group at a frequency of 2% or greater and with an incidence greater than that in the placebo group, regardless of causality, are presented in the following table:

Adverse Event Incidence Rates for All Treated Patients In All Placebo-Controlled Studies Adverse Event Zemplar (n = 62)
% Placebo (n = 51)
%
Overall 71 78
Cardiac Disorders    
    Palpitations 3.2 0.0
Gastrointestinal Disorders    
    Dry Mouth 3.2 2.0
    Gastrointestinal Hemorrhage 4.8 2.0
    Nausea 12.9 7.8
    Vomiting