Table 4. Mean Changes from Baseline to Final Treatment Visit in Serum iPTH, Bone Specific Alkaline Phosphatase, Calcium, Phosphorus, and Calcium x Phosphorus Product in Three Combined Double-Blind, Placebo-Controlled, Phase 3, CKD Stages 3 and 4 Studies   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)

Chronic Kidney Disease 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 weekly ≥ 30% reductions from baseline iPTH was 88% of Zemplar Capsules treated patients and 13% of the placebo treated patients. The proportion of patients achieving at least two consecutive weekly ≥ 30% reductions from baseline iPTH was similar for HD and PD patients.

The incidence of hypercalcemia (defined as two consecutive serum calcium values > 10.5 mg/dL) in patients treated with Zemplar Capsules was 6.6% as compared to 0% for patients given placebo. In PD patients the incidence of hypercalcemia in patients treated with Zemplar Capsules was 21% as compared to 0% for patients given placebo. The patterns of change in the mean values for serum iPTH are shown in Figure 2. The rate of hypercalcemia with Zemplar Capsules may be reduced with a lower dosing regimen based on the iPTH/80 formula as shown by computer simulations. The hypercalcemia rate can be further predicted to decrease, if the treatment is initiated in only those