o improved in patients treated with Sensipar®. These studies showed that Sensipar® reduced PTH while lowering Ca x P, calcium and phosphorus levels (Table 1, Figure 2). The median dose of Sensipar® at the completion of the studies was 90 mg. Patients with milder disease typically required lower doses.
Table 1. Effects of Sensipar® on iPTH, Ca x P, Serum Calcium, and Serum Phosphorus in 6-month Phase 3 Studies (Patients on Dialysis) Study 1 Study 2 Study 3
Placebo Sensipar® Placebo Sensipar® Placebo Sensipar®
(N = 205) (N = 205) (N = 165) (N = 166) (N = 101) (N = 294)
*
iPTH value based on averaging over the eva luation phase (defined as weeks 13 to 26 in studies 1 and 2 and weeks 17 to 26 in study 3)
Values shown are medians unless indicated otherwise
†
p < 0.001 compared to placebo; p-values presented for primary endpoint only
iPTH
Baseline (pg/mL): Median
Mean (SD) 535
651 (398) 537
636 (341) 556
630 (317) 547
652 (372) 670
832 (486) 703
848 (685)
eva luation Phase (pg/mL) 563 275 592 238 737 339
Median Percent Change +3.8 -48.3 +8.4 -54.1 +2.3 -48.2
Patients Achieving Primary Endpoint (iPTH ≤ 250 pg/mL) (%)* 4% 41%† 7% 46%† 6% 35%†
Patients Achieving ≥ 30% Reduction in iPTH (%)* 11% 61% 12% 68% 10% 59%
Patients Achieving iPTH ≤ 250 pg/mL and Ca x P < 55 mg2/dL2 (%) 1% 32% 5% 35% 5% 28%
Ca x P
Baseline (mg2/dL2) 62 61 61 61 61 59
eva luation Phase (mg2/dL2) 59 52 59 47 57 48
Median Percent Change -2.0 -14.9 -3.1 -19.7 -4.8 -15.7
Calcium
Baseline (mg/dL) 9.8 9.8 9.8 9.9 10.0 9.9 9.8
eva luation Phase (mg/dL) 9.9 9.9 9.1 9.9 9.1 10.0 9.1
Median Percent Change +0.5 +0.5 -5.5 +0.1 -7.4 +0.3 -6.0
Phosphorus
Baseline (mg/dL) 6.3 6.3 6.1 6.1 6.0 6.1 6.0
eva luation Phase (mg/dL) 6.0 6.0 5.6 5.9 5.1 5.6 5.3
Median Percent Change -1.0 -1.0 -9.0 -2.4 -12.4 -5.6 -8.6
Figure 1. Mean (SE) iPTH Values (Pooled Phase 3 Studies) Data are presented for patients who completed the studies;
Placebo (N = 342), Sensipar® (N = 439).
Figure 2. Mean (SE) Ca x P Values (Pooled Phase 3 Studies) Data are presented for patients who completed the studies; Placebo (N = 342), Sensipar® (N = 439).
Reductions in iPTH and Ca x P were maintained for up to 12 months of treatment.
Sensipar® decreased iPTH and Ca x P levels regardless of disease severity (i.e., baseline iPTH value), duration of dialysis, and whether or not vitamin D sterols were administered. Approximately 60% of patients with mild (iPTH ≥ 300 to ≤ 500 pg/mL), 41% with moderate (iPTH > 500 to 800 pg/mL), and 11% with severe (iPTH > 800 pg/mL) secondary HPT achieved a mean iPTH value of 250 pg/mL. Plasma iPTH levels were measured using the Nichols IRMA.
Parathyroid Carcinoma
Ten patients with parathyroid carcinoma were enrolled in an open-label study. The study consisted of 2 phases, a dose-titration phase and a maintenance phase.
The range of exposure was 2 to 16 weeks in the titration phase (n = 10) and 16 to 48 weeks (n = 3) for the mainten
