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:

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