Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Patients With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy
Condition: Hyperparathyroidism, Primary; Hypercalcemia
MeSH terms: Hypercalcemia; Hyperparathyroidism; Hyperparathyroidism, Primary
Intervention: Cinacalcet; Placebo
Intervention description: Administered orally at a starting dose of 30 mg twice a day (BID). Participants will be eligible for a dose titration once every 3 weeks during the placebo-controlled dose titration phase based on corrected total serum calcium concentration and safety assessments obtained the previous week. Doses may be sequentially increased to 60 mg BID, 90 mg BID, and 90 mg 3 times a day (TID).; Administered orally following the same tiitration regimen as the experimental arm.
Intervention MeSH terms: Cinacalcet
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Primary hyperparathyroidism; Parathyroidectomy; Hypercalcemia

Summary:

      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.
    

Eligibility criteria:

        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