Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism

Abstract

Context: Patients with persistent primary hyperparathyroidism (PHPT) after parathyroidectomy or with contraindications to parathyroidectomy often require chronic treatment for hypercalcemia.

Objective: The objective of the study was to assess the ability of the calcimimetic, cinacalcet, to reduce serum calcium in patients with intractable PHPT.

Design: This was an open-label, single-arm study comprising a titration phase of variable duration (2-16 wk) and a maintenance phase of up to 136 wk.

Setting: The study was conducted at 23 centers in Europe, the United States, and Canada.

Patients: The study included 17 patients with intractable PHPT and serum calcium greater than 12.5 mg/dl (3.1 mmol/liter).

Intervention: During the titration phase, cinacalcet dosages were titrated every 2 wk (30 mg twice daily to 90 mg four times daily) for 16 wk until serum calcium was 10 mg/dl or less (2.5 mmol/liter). If serum calcium increased during the maintenance phase, additional increases in the cinacalcet dose were permitted.

Main outcome measure: The primary end point was the proportion of patients experiencing a reduction in serum calcium of 1 mg/dl or greater (0.25 mmol/liter) at the end of the titration phase.

Results: Mean +/- sd baseline serum calcium was 12.7 +/- 0.8 mg/dl (3.2 +/- 0.2 mmol/liter). At the end of titration, a 1 mg/dl or greater reduction in serum calcium was achieved in 15 patients (88%). Fifteen patients (88%) experienced treatment-related adverse events, none of which were serious. The most common adverse events were nausea, vomiting, and paresthesias.

Conclusions: In patients with intractable PHPT, cinacalcet reduces serum calcium, is generally well tolerated, and has the potential to fulfill an unmet medical need.

Trial registration: ClinicalTrials.gov NCT00037518.

Figures

Figure 1

Algorithm for dose titration. During the study, new dose strengths of cinacalcet were manufactured. Patients receiving either 50-mg or 70-mg dosages were switched to a 60-mg dosage regimen. Thus, patients receiving 50 mg twice a day (BID) or 70 mg BID were switched to 60 mg BID, patients receiving 70 mg three times a day (TID) were switched to 60 mg TID, and patients receiving 70 mg four times a day (QID) were switched to 60 mg QID.

Figure 2

Mean (± se) predose serum calcium concentration (A) and mean (± se) predose plasma iPTH concentration (B) at each visit are shown. The end of the titration phase (EOTP) was of variable duration (2–16 wk). The maintenance phase was 136 wk, but data are shown to wk 80 (i.e. where data were available for two or more patients). Shaded areas represent the normal ranges for serum calcium [8.4–10.3 mg/dl (2.1–2.6 mmol/liter)] (A) and iPTH [10–65 pg/ml (1.1–6.9 pmol/liter)] (B). B, Baseline.

Figure 3

Percentages of patients (rounded to the closest integer) with improvement or worsening in the eight SF-36 scales from baseline to the end of the titration period (n = 17). Improved, Increase in score from baseline of 3 or more points; same, increase or decrease in score from baseline of less than 3 points; worsened, decrease in score from baseline of 3 or more points.