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

A Randomized Double-blind Placebo-controlled Study to Evaluate the Efficacy and Safety of Cinacalcet for the Treatment of Hypercalcemia in Subjects With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy

This study is designed to demonstrate the efficacy and to assess the safety of cinacalcet for the reduction of hypercalcemia in patients with primary hyperparathyroidism for whom parathyroidectomy is indicated on the basis of an elevated corrected total serum calcium, but who are 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:

  1. 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

  2. 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