Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Patients With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy

The study will consist of a 30-day screening phase, a 12-week placebo-controlled dose-titration phase, and a 16-week placebo-controlled efficacy assessment phase (EAP). Participants who complete 28 weeks on study will continue into an open-label safety extension phase for 24 weeks of investigational cinacalcet treatment.

Inclusion criteria

• age ≥ 18 years
• diagnosis of primary hyperparathyroidism (HPT)
• subjects must have the following laboratory values:

• local/historical laboratory result showing a corrected total serum calcium > 1 mg/dL (0.25 mmol/L) above the upper limit of normal and

≤ 12.5 mg/dL (3.12 mmol/L) within the past 12 months, and

• local/historical laboratory result showing a plasma parathyroid horone (PTH) > 75% of upper limit of normal within the past 12 months, and
• one central laboratory draw at the screen visit showing a corrected total serum calcium > 11.3 mg/dL (2.82 mmol/L) and ≤ 12.5 mg/dL (3.12 mmol/L), and
• one central laboratory draw at the screen visit showing a plasma PTH > 55 pg/mL (5.8 pmol/L) OR
• two central laboratory draws performed during the screening period at least 7 days apart, showing a

• corrected total serum calcium > 11.3 mg/dL (2.82 mmol/L) and ≤ 12.5 mg/dL (3.12 mmol/L), and
• plasma PTH > 55 pg/mL (5.8 pmol/L)
• not able to undergo parathyroidectomy for ≥ 1 of the following reasons:

• failed parathyroidectomy
• comorbid conditions contraindicating parathyroidectomy
• parathyroidectomy not considered appropriate or is not feasible by primary physician and subject
• before any study-specific procedure is performed, the appropriate written informed consent must be obtained

Exclusion criteria

• symptoms attributable to hypercalcemia, requiring immediate medical intervention, as judged by the investigator (including acute kidney stone, nausea and vomiting requiring intravenous hydration, confusion, lethargy, stupor, or coma)
• unstable medical condition, defined as having been hospitalized within 30 days before the date of informed consent, or otherwise unstable in the judgment of the investigator
• administration of drugs that increase serum calcium concentration, including but not limited to thiazide diuretics or lithium
• initiated bisphosphonate therapy or changed bisphosphonate dose within 12 weeks before the date of informed consent
• current administration of drugs for ventricular arrhythmia
• unable to provide informed consent, or is at risk for poor compliance with study procedures
• currently enrolled in another investigational device or drug study(s), or completed such study within 30 days before the date of informed consent
• known hypersensitivity to or unable to tolerate cinacalcet
• received treatment with cinacalcet within 60 days before the date of informed consent
• history of seizures or an adjustment of anti-seizure medication within 12 weeks before the date of informed consent
• family history or diagnosis a genetic syndrome, such as familial benign hypocalciuric hypercalcemia (FBHH) or multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2), where primary HPT is one of the clinical manifestations of familial benign hypocalciuric hypercalcemia (FBHH)
• refused to use highly effective contraceptive measures (as determined by the investigator) throughout the study
• pregnant or breastfeeding