ents associated with hypercalcemia or hyperphosphatemia in the Zemplar Capsules group. No increases in urinary calcium or phosphorous were detected in Zemplar Capsules treated patients compared to placebo.
The pattern of change in the mean values for serum iPTH during the studies are shown in Figure 1.
Figure 1. Mean Values for Serum iPTH Over Time in the Three Double-Blind, Placebo-Controlled, Phase 3, CKD Stage 3 and 4 Studies Combined
The mean changes from baseline to final treatment visit in serum iPTH, calcium, phosphorus, calcium-phosphorus product (Ca x P), and bone-specific alkaline phosphatase are shown in Table 2.
Table 2. Mean Changes from Baseline to Final Treatment Visit in Serum iPTH, Bone Specific Alkaline Phosphatase, Calcium, Phosphorus, and Calcium x Phosphorus Product in Three Double-Blind, Placebo-Controlled, Phase 3, CKD Stage 3 and 4 Studies Combined Zemplar Capsules Placebo
iPTH (pg/mL) n = 104 n = 110
Mean Baseline Value 266 279
Mean Final Treatment Value 162 315
Mean Change from Baseline (SE) -104 (9.2) +35 (9.0)
Bone Specific Alkaline Phosphatase (mcg/L) n = 101 n = 107
Mean Baseline 17.1 18.8
Mean Final Treatment Value 9.2 17.4
Mean Change from Baseline (SE) -7.9 (0.76) -1.4 (0.74)
Calcium (mg/dL) n = 104 n = 110
Mean Baseline 9.3 9.4
Mean Final Treatment Value 9.5 9.3
Mean Change from Baseline (SE) +0.2 (0.04) -0.1 (0.04)
Phosphorus (mg/dL) n = 104 n = 110
Mean Baseline 4.0 4.0
Mean Final Treatment Value 4.3 4.3
Mean Change from Baseline (SE) +0.3 (0.08) +0.3 (0.08)
Calcium x Phosphorus Product (mg2/dL2) n = 104 n = 110
Mean Baseline 36.7 36.9
Mean Final Treatment Value 40.7 39.7
Mean Change from Baseline (SE) +4.0 (0.74) +2.9 (0.72)
CKD Stage 5
The safety and efficacy of Zemplar Capsules were eva luated in a Phase 3, 12-week, double blind, placebo-controlled, randomized, multicenter study in patients with CKD Stage 5 on HD or PD. The study used a three times a week dosing design. A total of 61 patients received Zemplar Capsules and 27 patients received placebo. The mean age of the patients was 57 years, 67% were male, 50% were Caucasian, 45% were African-American, and 53% were diabetic. The average baseline iPTH was 701 pg/mL (range: 216-1933 pg/mL). The average time since first dialysis across all subjects was 3.3 years.
The initial dose of Zemplar Capsules was based on baseline iPTH/60. Subsequent dose adjustments were based on iPTH/60 as well as primary chemistry results that were measured once a week. Starting at Treatment Week 2, study drug was maintained, increased or decreased weekly based on the results of the previous week’s calculation of iPTH/60. Zemplar Capsules were administered three times a week, not more than every other day.
The proportion of patients achieving at least two consecutive ≥ 30% reductions from baseline iPTH was achieved by 88% of Zemplar Capsules treated patients and 13% of the placebo treated patients. The proportion of patients achieving at least two consecutive ≥ 30% reductions from baseline iPTH was similar for HD and PD patients.
The incidences of hypercalcemia (defined as two consecutive serum calcium values > 10.5 mg/dL) in patients treated |
