Cinacalcet HCl reduces hypercalcemia in primary hyperparathyroidism across a wide spectrum of disease severity

Abstract

Context: Primary hyperparathyroidism (PHPT) is characterized by elevated serum calcium (Ca) and increased PTH concentrations.

Objective: The objective of the investigation was to establish the efficacy of cinacalcet in reducing serum Ca in patients with PHPT across a wide spectrum of disease severity.

Design and setting: The study was a pooled analysis of data from three multicenter clinical trials of cinacalcet in PHPT.

Patients: Patients were grouped into three disease categories for analysis based on the following: 1) history of failed parathyroidectomy (n = 29); 2) meeting one or more criteria for parathyroidectomy but without prior surgery (n = 37); and 3) mild asymptomatic PHPT without meeting criteria for either above category (n = 15).

Intervention: The intervention in this study was treatment with cinacalcet for up to 4.5 yr.

Outcomes: Measurements in the study included serum Ca, PTH, phosphate, and bone-specific alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study period.

Results: The extent of cinacalcet-induced serum Ca reduction, proportion of patients achieving normal serum Ca (≤10.3 mg/dl), reduction in serum PTH, and increase in serum phosphate were similar across all three categories. Except for decreased aBMD at the total femur indicated for parathyroidectomy group at 1 yr, no significant changes in aBMD occurred. The efficacy of cinacalcet was maintained for up to 4.5 yr of follow-up. AEs were mild and similar across the three categories.

Conclusions: Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated.

Trial registration: ClinicalTrials.gov NCT00001859 NCT00037518 NCT00936988.

Figure 1

Study design showing the source of subjects for categorizing into disease severity. bid, Two times per day; qid, four times per day; qd, once per day; #, number.

Figure 2

Predose serum Ca, PTH, and BMD (mean ± se) over time during the 4 yr on the trial. Fasting samples were taken approximately 12 h after the prior evening dose of placebo or cinacalcet. A, Serum Ca. The shaded region represents the normal reference range. B, Plasma PTH. The shaded region represents the normal reference range. C, Total femur. D, Lumbar spine. E, Distal one third radius. The numbers of subjects (N) during each year of the study are shown for the failed parathyroidectomy groups (closed circles), indicated for parathyroidectomy groups (open circles), and asymptomatic groups (open squares). BL, Baseline. *, P < 0.05; **, P < 0.01; ***, P < 0.0001 compared with baseline (Wilcoxon signed ranks).

Figure 2a

Continued.

Figure 3

Proportion of subjects with normocalcemia (8.4–10.3 mg/dl) at 6 months and 1, 2, 3, and 4 yr in the failed parathyroidectomy, indicated for parathyroidectomy, and asymptomatic groups. BL, Baseline.