Patients with persistent PHPT after parathyroidectomy (PTX) or contraindications for PTX often require chronic treatment for hypercalcemia, representing an unmet medical need. In an open-label, single-arm study in the US and EU, 17 patients underwent a variable length titration phase (maximum 16 weeks) with a maintenance phase (MP) of up to 3 years. Patients were eligible if they had (1) persistent PHPT following PTX or were considered contraindicated for PTX, and (2) serum calcium (sCa) >3.1 mmol/l (12.4 mg/dl). Possible dose increases occurred every 2 weeks during a titration phase until sCa ≤2.5 mmol/l (10.0 mg/dl), or the patient reached the highest dose (90 mg qid) allowed, or adverse events (AEs) precluded further dose increases. The primary endpoint of sCa reduction by ≥0.25 mmol/l (1 mg/dl) at the end of titration (EOT) was reached by 15 patients, while 9 reached the secondary endpoint of sCa reduction to ≤2.6 mmol/l (10.3 mg/dl) at the EOT. Mean values (SE) for sCa and iPTH showed a decrease in sCa and a rise in iPTH. However, median iPTH (Q1, Q3) decreased from 29.3 pmol/l (14.9, 33.0) at baseline to 19.0 pmol/l (14.4, 32.4) at EOT. Three patients were treated for up to 72 weeks in the maintenance phase, at which point mean (SE) sCa was 2.5 (0.23) mmol/l and mean (SE) iPTH was 11.9 (4.5) pmol/l. The most frequent treatment-related AEs were nausea, vomiting, and paresthesia. Only 1 patient had a treatment-related adverse event that led to withdrawal from the study.
|Baseline||End of titration|
|Mean sCa (S.E.M.)||3.2 (0.05) mmol/l, N=17||2.6 (0.08) mmol/l, N=17|
|Mean iPTH (S.E.M.)||26.7 (2.9) pmol/l, N=16||43.5 (17.4) pmol/l, N=15|
In conclusion, cinacalcet addresses an unmet need in patients with PHPT and hypercalcemia for which no approved therapy exists.
03 - 07 May 2008
European Society of Endocrinology