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

Hypercalcemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00975221
• Other study ID #: 20070277
• Status: Completed
• Phase: Phase 3
• Start date: March 10, 2010
• Est. completion date: December 21, 2012

Study information

• Verified date: September 2018
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: December 21, 2012
• Est. primary completion date: July 12, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypercalcemia
• Hyperparathyroidism
• Hyperparathyroidism, Primary

Intervention

Drug:
• Cinacalcet
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).
• Placebo
Administered orally following the same tiitration regimen as the experimental arm.

Locations

Country	Name	City	State
Australia	Research Site	Footscray	Victoria
Australia	Research Site	Geelong	Victoria
Australia	Research Site	Nedlands	Western Australia
Australia	Research Site	Randwick	New South Wales
Australia	Research Site	St Leonards	New South Wales
Canada	Research Site	Calgary	Alberta
Canada	Research Site	London	Ontario
Canada	Research Site	Oakville	Ontario
Canada	Research Site	Toronto	Ontario
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Szeged
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Portugal	Research Site	Coimbra
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Rostov-na-Dony
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Yaroslavl
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Aventura	Florida
United States	Research Site	Clearwater	Florida
United States	Research Site	Columbus	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kenner	Louisiana
United States	Research Site	Lake Forest	California
United States	Research Site	Lancaster	California
United States	Research Site	Los Gatos	California
United States	Research Site	Miami	Florida
United States	Research Site	Mission Viejo	California
United States	Research Site	Morehead City	North Carolina
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New York	New York
United States	Research Site	Orange	California
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	San Diego	California
United States	Research Site	Washington	District of Columbia
United States	Research Site	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hungary,  Poland,  Portugal,  Russian Federation, 

References & Publications (1)

Khan A, Bilezikian J, Bone H, Gurevich A, Lakatos P, Misiorowski W, Rozhinskaya L, Trotman ML, Tóth M. Cinacalcet normalizes serum calcium in a double-blind randomized, placebo-controlled study in patients with primary hyperparathyroidism with contraindications to surgery. Eur J Endocrinol. 2015 May;172(5):527-35. doi: 10.1530/EJE-14-0877. Epub 2015 Jan 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP		Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)

External Links

•   AmgenTrials clinical trials website