A Multi-Center, Randomized, Open-Label Study to Assess the Immunogenicity and Safety of Denosumab in Pre-filled Syringe Compared to Vial in Subjects With Low Bone Mineral Density

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00515463
First received: August 9, 2007
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to compare the immunogenicity profiles of denosumab pre-filled syringe (PFS) and vial at 6 months in postmenopausal women with low bone mineral density (BMD).


Condition Intervention Phase
Low Bone Mineral Density
Osteopenia
Osteoporosis
Biological: denosumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center, Randomized, Open-Label Study to Assess the Immunogenicity and Safety of Denosumab in Pre-filled Syringe Compared to Vial in Subjects With Low Bone Mineral Density

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Number of Participants Who Tested Positive for Anti-denosumab Antibodies at Month 6 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    An electrochemiluminescent bridging immunoassay was used to test blood samples for binding antibodies to denosumab.


Secondary Outcome Measures:
  • Number of Participants Who Tested Positive for Anti-denosumab Antibodies at Month 12 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    An electrochemiluminescent bridging immunoassay was used to test blood samples for binding antibodies to denosumab.

  • Number of Participants With Neutralizing Antibodies Against Denosumab at Month 12 [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
    Samples demonstrating reactivity for binding antibodies to denosumab were to be tested for neutralizing or inhibitory effects in a cell-based bioassay.

  • Sodium Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry sodium

  • Sodium Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry sodium

  • Sodium Change From Baseline at Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: Yes ]
    Sodium Change From Baseline at Month 12

  • Potassium Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry potassium

  • Potassium Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry potassium

  • Potassium Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry potassium

  • Chloride Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry chloride

  • Chloride Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry chloride

  • Chloride Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry chloride

  • Bicarbonate Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry bicarbonate

  • Bicarbonate Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry bicarbonate

  • Bicarbonate Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry bicarbonate

  • Magnesium Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry magnesium

  • Magnesium Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry magnesium

  • Magnesium Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry magnesium

  • Blood Urea Nitrogen Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry blood urea nitrogen

  • Blood Urea Nitrogen Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry blood urea nitrogen

  • Blood Urea Nitrogen Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry blood urea nitrogen

  • Creatinine Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry creatinine

  • Creatinine Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry creatinine

  • Creatinine Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry creatinine

  • Aspartate Amino Transferase Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry aspartate amino transferase

  • Aspartate Amino Transferase Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry aspartate amino transferase

  • Aspartate Amino Transferase Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry aspartate amino transferase

  • Alanine Amino Transferase Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry alanine amino transferase

  • Alanine Amino Transferase Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry alanine amino transferase

  • Alanine Amino Transferase Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry alanine amino transferase

  • Total Bilirubin Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry total bilirubin

  • Total Bilirubin Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry total bilirubin

  • Total Bilirubin Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry total bilirubin

  • Albumin Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry albumin

  • Albumin Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry albumin

  • Albumin Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry albumin

  • Total Protein Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry total protein

  • Total Protein Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry total protein

  • Total Protein Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry total protein

  • Glucose Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry glucose

  • Glucose Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry glucose

  • Glucose Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory chemistry glucose

  • Red Blood Cells Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology red blood cells

  • Red Blood Cells Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology red blood cells

  • Red Blood Cells Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology red blood cells

  • Hemoglobin Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology hemoglobin

  • Hemoglobin Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology hemoglobin

  • Hemoglobin Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology hemoglobin

  • Reticulocytes Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology reticulocytes

  • Reticulocytes Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology reticulocytes

  • Reticulocytes Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology reticulocytes

  • Platelets Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology platelets

  • Platelets Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology platelets

  • Platelets Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology platelets

  • White Blood Cells Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology white blood cells

  • White Blood Cells Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology white blood cells

  • White Blood Cells Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology white blood cells

  • Total Neutrophils Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology total neutrophils

  • Total Neutrophils Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology total neutrophils

  • Total Neutrophils Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology total neutrophils

  • Eosinophils Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology eosinophils

  • Eosinophils Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology eosinophils

  • Eosinophils Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology eosinophils

  • Basophils Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology basophils

  • Basophils Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology basophils

  • Basophils Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology basophils

  • Lymphocytes Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology lymphocytes

  • Lymphocytes Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology lymphocytes

  • Lymphocytes Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology lymphocytes

  • Monocytes Change From Baseline at Month 1 [ Time Frame: Baseline, month 1 ] [ Designated as safety issue: Yes ]
    Laboratory hematology monocytes

  • Monocytes Change From Baseline at Month 6 [ Time Frame: Baseline, month 6 ] [ Designated as safety issue: Yes ]
    Laboratory hematology monocytes

  • Monocytes Change From Baseline at Month 12 [ Time Frame: Baseline, month 12 ] [ Designated as safety issue: Yes ]
    Laboratory hematology monocytes

  • Number of Participants With Laboratory Toxicity CTCAE Grade Greater or Equal to 3 [ Time Frame: Day 1 to Month 12 ] [ Designated as safety issue: Yes ]
    Participants with laboratory toxicity grade 3 (severe) or 4 (life-threatening), based on the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.


Enrollment: 311
Study Start Date: May 2007
Study Completion Date: March 2009
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denosumab - Vial
Participants received denosumab 60 mg subcutaneous injection using a standard vial on Day 1 and at Month 6.
Biological: denosumab
60 mg denosumab in 1mL
Experimental: Denosumab - Prefilled syringe
Participants received denosumab 60 mg subcutaneous injection using a pre-filled syringe on Day 1 and at Month 6.
Biological: denosumab
60 mg denosumab in 1mL

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who have successfully completed the 20050141 study (NCT00330460):

    • Must have received all SC investigational product administrations in 20050141
    • Must not have taken any proscribed therapies in 20050141
    • Subjects who were in the alendronate or denosumab treatment group are allowed
  • Provide signed informed consent before any study-specific procedures are conducted

Exclusion Criteria:

  • Any disorder that, in the opinion of the investigator, may compromise the ability of the patient to give written informed consent and/or comply with study procedures including:

    • Any physical or psychiatric disorder
    • Or evidence of alcohol or substance abuse in the last 12 months
  • Any clinical evidence, in the medical judgement of the investigator, of the following medical conditions:

    • Impaired thyroid function (subsequent to treatment)
    • Impaired hepatic function
    • Impaired renal function
    • Rheumatoid Arthritis, Paget's disease, Cushing's disease, hyperprolactinemia, or cirrhosis of the liver
    • Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen
    • Any metabolic bone disease, eg, osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00515463

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00515463     History of Changes
Other Study ID Numbers: 20060237
Study First Received: August 9, 2007
Results First Received: June 18, 2010
Last Updated: August 27, 2013
Health Authority: Canada: Health Canada
United States: Food and Drug Administration
United States: Schulman Associates IRB

Keywords provided by Amgen:
Osteopenia
Osteoporosis
AMG 162
Postmenopausal
Pre-filled syringe

Additional relevant MeSH terms:
Bone Diseases, Metabolic
Osteoporosis
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on April 17, 2014