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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hyperparathyroidism, Primary, Hypercalcemia

Intervention / Treatment
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* Drug: Cinacalcet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cinacalcet<br>Participants received cinacalcet at a starting dose of 30 mg orally BID and were eligible for a dose titration once every 3 weeks during the 12-week dose-titration phase based on corrected total serum calcium concentration and safety assessments. Participants continued to receive cinacalcet for another 16 weeks during the efficacy assessment phase and then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52. | Drug: Cinacalcet<br>* 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).<br>* Other names: Mimpara;|
| Placebo Comparator: Placebo<br>Participants received placebo orally twice a day (BID) for 12 weeks during the dose titration phase and for another 16 weeks during the efficacy assessment phase. Participants then continued into the open-label extension phase and received cinacalcet at a starting dose of 30 mg BID for 24 weeks. The dose of cinacalcet could have been increased or decreased as needed to maintain a corrected total serum calcium concentration within the normal range through Week 52. | Drug: Cinacalcet<br>* 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).<br>* Other names: Mimpara;Drug: Placebo<br>* Administered orally following the same tiitration regimen as the experimental arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP |  | Efficacy assessment phase (study visits at Weeks 16, 20, 24, and 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a ≥ 1 mg/dL (0.25 mmol/L) Decrease From Baseline in Mean Corrected Total Serum Calcium Concentration During the EAP |  | Baseline and the EAP (mean of Weeks 16, 20, 24, and 28) | 
| Percent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP |  | Baseline and the EAP (mean of Weeks 16, 20, 24, and 28) | 
| Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP |  | Baseline and the EAP (mean of Weeks 16, 20, 24, and 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary hyperparathyroidism, Parathyroidectomy, Hypercalcemia