General Information

Sensipar is an oral calcimimetic medication that lowers the levels of parathyroid hormone, phosphorous and calcium in patients undergoing kidney dialysis or in patients with parathroid cancer.

Sensipar is indicated for the treatment of secondary hyperparathyroidism in chronic kidney disease patients on dialysis and the treatment of elevated calcium levels (hypercalcemia) in patients with parathyroid carcinoma.

Mechanism of Action

Cinacalcet is an oral calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. The calcium-sensing receptors on the surface of parathyroid gland cells also regulate parathyroid hormone (PTH) secretion. Increased PTH stimulates osteoclastic activity resulting in cortical bone resorption and marrow fibrosis. Increasing the sensitivity of these receptors results in a lowering of PTH which subsequently lowers serum calcium levels. In addition, significant reductions in calcium may lower the threshold for seizures.

Side Effects

Adverse events associated with the use of Sensipar may include (but are not limited to) the following:

• nausea
• vomiting
• diarrhea
• myalgia
• dizziness
• hypertension
• asthenia

Dosing/Administration

The recommended starting oral dose of Sensipar is 30 mg once daily.

Clinical Trial Results

FDA approval of Sensipar was based on three multicenter, randomized, double-blind, placebo-controlled studies enrolling a total of 1,136 chronic kidney disease (CKD) subjects on dialysis. Among the subjects, 96 percent were on hemodialysis and 4 percent were on peritoneal dialysis. Upon enrollment, 66 percent of the subjects were receiving vitamin D sterols and 93 percent were receiving phosphate binders. The average duration of dialysis prior to study enrollment was 67 months. Treatment was administered at a dose of 30 mg once daily and titrated every three or four weeks to a maximum dose of 180 mg once daily to achieve an intact PTH (iPTH) of = 250 pg/mL. Results showed that 40 percent of subjects taking Sensipar achieved an iPTH = 250 pg/mL compared with 5 percent on placebo. Data showed that Sensipar reduced PTH while lowering Ca x P, calcium and phosphorus levels. Secondary efficacy parameters also improved in patients treated with Sensipar.

An open-label study in 10 subjects with parathyroid carcinoma consisted of a dose-titration phase and a maintenance phase. The doses ranged from 70 mg twice daily to 90 mg four times daily for patients in the maintenance phase. The range of exposure was two to 16 weeks in the titration phase and 16 to 48 weeks for the maintenance phase. Baseline mean (SD) serum calcium was 14.7 mg/dL. The range of change from baseline to last measurement was –7.5 to 2.7 mg/dL during the titration phase and –7.4 to 0.9 mg/dL during the maintenance phase (Figure 3). No patients maintained a serum calcium level within the normal range.