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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on October 19, 2014