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

Primary Purpose

Hyperparathyroidism, Primary, Hypercalcemia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cinacalcet
Placebo
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyperparathyroidism, Primary focused on measuring Primary hyperparathyroidism, Parathyroidectomy, Hypercalcemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cinacalcet

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP

Secondary Outcome Measures

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
Percent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP
Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP

Full Information

First Posted
September 10, 2009
Last Updated
September 20, 2018
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT00975221
Brief Title
Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Patients With Primary Hyperparathyroidism Unable to Undergo Parathyroidectomy
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
March 10, 2010 (Actual)
Primary Completion Date
July 12, 2012 (Actual)
Study Completion Date
December 21, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperparathyroidism, Primary, Hypercalcemia
Keywords
Primary hyperparathyroidism, Parathyroidectomy, Hypercalcemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cinacalcet
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cinacalcet
Other Intervention Name(s)
Sensipar, Mimpara
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered orally following the same tiitration regimen as the experimental arm.
Primary Outcome Measure Information:
Title
Percentage of Participants With Mean Corrected Total Serum Calcium Concentration ≤ 10.3 mg/dL (2.57 mmol/L) During the EAP
Time Frame
Efficacy assessment phase (study visits at Weeks 16, 20, 24, and 28)
Secondary Outcome Measure Information:
Title
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
Time Frame
Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)
Title
Percent Change From Baseline in Corrected Total Serum Calcium Concentration During the EAP
Time Frame
Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)
Title
Percent Change From Baseline in Plasma Parathyroid Hormone Level During the EAP
Time Frame
Baseline and the EAP (mean of Weeks 16, 20, 24, and 28)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Lake Forest
State/Province
California
ZIP/Postal Code
92630
Country
United States
Facility Name
Research Site
City
Lancaster
State/Province
California
ZIP/Postal Code
93534
Country
United States
Facility Name
Research Site
City
Los Gatos
State/Province
California
ZIP/Postal Code
95032
Country
United States
Facility Name
Research Site
City
Mission Viejo
State/Province
California
ZIP/Postal Code
92691
Country
United States
Facility Name
Research Site
City
Orange
State/Province
California
ZIP/Postal Code
92869
Country
United States
Facility Name
Research Site
City
San Diego
State/Province
California
ZIP/Postal Code
92124
Country
United States
Facility Name
Research Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Research Site
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
Research Site
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Facility Name
Research Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32204
Country
United States
Facility Name
Research Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33145
Country
United States
Facility Name
Research Site
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Facility Name
Research Site
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Research Site
City
Kenner
State/Province
Louisiana
ZIP/Postal Code
70065
Country
United States
Facility Name
Research Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48236
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Research Site
City
Morehead City
State/Province
North Carolina
ZIP/Postal Code
28557
Country
United States
Facility Name
Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1296
Country
United States
Facility Name
Research Site
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Research Site
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Research Site
City
Footscray
State/Province
Victoria
ZIP/Postal Code
3011
Country
Australia
Facility Name
Research Site
City
Geelong
State/Province
Victoria
ZIP/Postal Code
3220
Country
Australia
Facility Name
Research Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Research Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
Research Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4V2
Country
Canada
Facility Name
Research Site
City
Oakville
State/Province
Ontario
ZIP/Postal Code
L6J 1X8
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5C 2T2
Country
Canada
Facility Name
Research Site
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Research Site
City
Budapest
ZIP/Postal Code
1088
Country
Hungary
Facility Name
Research Site
City
Budapest
ZIP/Postal Code
1113
Country
Hungary
Facility Name
Research Site
City
Szeged
ZIP/Postal Code
6720
Country
Hungary
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
01-809
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
02-507
Country
Poland
Facility Name
Research Site
City
Coimbra
ZIP/Postal Code
3000-075
Country
Portugal
Facility Name
Research Site
City
Lisboa
ZIP/Postal Code
1350-179
Country
Portugal
Facility Name
Research Site
City
Lisboa
ZIP/Postal Code
1649-035
Country
Portugal
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
117036
Country
Russian Federation
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
119034
Country
Russian Federation
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
129110
Country
Russian Federation
Facility Name
Research Site
City
Rostov-na-Dony
ZIP/Postal Code
344022
Country
Russian Federation
Facility Name
Research Site
City
Saint Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
Research Site
City
Yaroslavl
ZIP/Postal Code
150003
Country
Russian Federation

12. IPD Sharing Statement

Citations:
PubMed Identifier
25637076
Citation
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.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

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

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