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

NCT ID: NCT00975221

Last Updated: 2018-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-10
• Study Completion Date: 2012-12-21

Brief 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.

Detailed 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.

Conditions

Hyperparathyroidism, Primary; Hypercalcemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cinacalcet

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.

Group Type: EXPERIMENTAL

Cinacalcet

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Cinacalcet

Intervention Type: DRUG

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

Intervention Type: DRUG

Administered orally following the same tiitration regimen as the experimental arm.

Interventions

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).

Intervention Type: DRUG

Placebo

Administered orally following the same tiitration regimen as the experimental arm.

Intervention Type: DRUG

Other Intervention Names

Sensipar; Mimpara

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Research Site

Lake Forest, California, United States

Research Site

Lancaster, California, United States

Research Site

Los Gatos, California, United States

Research Site

Mission Viejo, California, United States

Research Site

Orange, California, United States

Research Site

San Diego, California, United States

Research Site

Aurora, Colorado, United States

Research Site

Washington D.C., District of Columbia, United States

Research Site

Aventura, Florida, United States

Research Site

Clearwater, Florida, United States

Research Site

Jacksonville, Florida, United States

Research Site

Miami, Florida, United States

Research Site

Pembroke Pines, Florida, United States

Research Site

Weston, Florida, United States

Research Site

Atlanta, Georgia, United States

Research Site

Indianapolis, Indiana, United States

Research Site

Kenner, Louisiana, United States

Research Site

New Orleans, Louisiana, United States

Research Site

Detroit, Michigan, United States

Research Site

New York, New York, United States

Research Site

Morehead City, North Carolina, United States

Research Site

Columbus, Ohio, United States

Research Site

Randwick, New South Wales, Australia

Research Site

St Leonards, New South Wales, Australia

Research Site

Footscray, Victoria, Australia

Research Site

Geelong, Victoria, Australia

Research Site

Nedlands, Western Australia, Australia

Research Site

Calgary, Alberta, Canada

Research Site

London, Ontario, Canada

Research Site

Oakville, Ontario, Canada

Research Site

Toronto, Ontario, Canada

Research Site

Budapest, , Hungary

Research Site

Budapest, , Hungary

Research Site

Budapest, , Hungary

Research Site

Szeged, , Hungary

Research Site

Warsaw, , Poland

Research Site

Warsaw, , Poland

Research Site

Warsaw, , Poland

Research Site

Coimbra, , Portugal

Research Site

Lisbon, , Portugal

Research Site

Lisbon, , Portugal

Research Site

Moscow, , Russia

Research Site

Moscow, , Russia

Research Site

Moscow, , Russia

Research Site

Rostov-na-Dony, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Yaroslavl, , Russia

Countries

United States; Australia; Canada; Hungary; Poland; Portugal; Russia

References

Khan A, Bilezikian J, Bone H, Gurevich A, Lakatos P, Misiorowski W, Rozhinskaya L, Trotman ML, Toth 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.

Reference Type: BACKGROUND

PMID: 25637076 (View on PubMed)

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20070277

Identifier Type: -

Identifier Source: org_study_id