Study to Compare the Efficacy and Safety of DenosumAb Versus Placebo in Males With Osteoporosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00980174
First received: September 17, 2009
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to assess how effective and safe denosumab is in a population of males with low bone mass at risk of fracture. The primary clinical hypothesis is that in men with low bone mineral density, the mean percent change in lumbar spine bone mineral density at 12 months in subjects receiving denosumab will be greater than in subjects receiving placebo. Denosumab is a fully human monoclonal antibody with a high affinity for Receptor Activator of Nuclear Factor (RANK) Ligand that can bind and neutralize the activity of human RANK Ligand similar to the action of endogenous osteoprotegerin.


Condition Intervention Phase
Low Bone Mass
Low Bone Mineral Density
Males With Osteoporosis
Osteopenia
Osteoporosis
Drug: 60 mg denosumab
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Compare the Efficacy and Safety of Denosumab Versus Placebo in Males With Low Bone Mineral Density

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: From Baseline to 12 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: From Baseline to 12 Months ] [ Designated as safety issue: No ]
  • Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: From Baseline to 12 Months ] [ Designated as safety issue: No ]
  • Trochanter Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: From Baseline to 12 Months ] [ Designated as safety issue: No ]
  • Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12 [ Time Frame: From Baseline to 12 Months ] [ Designated as safety issue: No ]
  • Serum Type 1 Collagen C-telopeptide (CTX) Percent Change From Baseline at Day 15 [ Time Frame: From Baseline to Day 15 ] [ Designated as safety issue: No ]

Enrollment: 242
Study Start Date: October 2009
Study Completion Date: July 2012
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 2
Subjects will receive placebo for denosumab (SC injection every 6 months) for 1 year (double-blind phase) followed by 60 mg denosumab (SC injection every 6 months) for 1 year (open-label phase)
Drug: 60 mg denosumab
60 mg denosumab (SC injection every 6 months)
Other Name: denosumab
Other: Placebo
Placebo for denosumab (SC injection every 6 months)
Experimental: 1
60 mg denosumab (SC injection every 6 months) for 1 year (double-blind phase) followed by 60 mg denosumab(SC injection every 6 months) for 1 year (open-label phase). These subjects will be on denosumab for a total of 2 years.
Drug: 60 mg denosumab
60 mg denosumab (SC injection every 6 months)
Other Name: denosumab

  Eligibility

Ages Eligible for Study:   30 Years to 85 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Bone Mineral Density (BMD) values (g/cm2) assessed by the local site at either the lumbar spine OR femoral neck that occur within the ranges specified in the protocol OR For subjects with a history of a major osteoporotic fracture (clinical vertebral, hip, humerus and distal radius fractures) occurring more than 6 months prior to screening, BMD values (g/cm2) assessed by the local site, at either the lumbar spine OR femoral neck that occur within the ranges specified in the protocol.
  • At least 2 lumbar vertebrae, at least 1 hip and at least one forearm must be evaluable by Dual X ray Absorptiometry (DXA).
  • Ambulatory males 30 to 85 years of age inclusive at the start of screening.
  • Provide the appropriate written informed consent before any study specific procedure.

Exclusion Criteria:

  • BMD values (g/cm2) as specified in the protocol in subjects with or without a history of major osteoporotic fractures, based on the particular scanner that is used.
  • Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
  • Any severe or more than 1 moderate vertebral fractures on screening spinal x ray
  • Any vertebral fracture diagnosed within the 6 months prior to screening
  • Any clinical fracture within the last 6 months prior to screening
  • For males with a partner of childbearing potential: Subject refuses to use 2 highly effective methods of contraception for the duration of the study and for 10 months after the last dose of study medication.
  • For males with a partner who is pregnant: Subject refuses to use a condom for the duration of the study and for 10 months after the last dose of study medication.
  • Previous participation in clinical trials with denosumab or administration of commercial denosumab.
  • Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).
  • Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (< 49.9 nmol/L)]. Vitamin D replenishment will be permitted and subjects may be re-screened; see Section 7.
  • Hyper- or hypothyroidism; however, stable subjects, in the investigator's opinion, on thyroid hormone replacement therapy are allowed.
  • Hyper- or hypoparathyroidism. Intact parathyroid hormone (iPTH) values outside of the reference range as determined by the central laboratory
  • Elevated transaminases. Serum aspartate aminotransferase; serum glutamate-oxaloacetic transaminase > 2.5 x upper limit of normal. Serum alanine aminotransferase; serum glutamate pyruvate transaminase > 2.5 x upper limit of normal (both as determined by the central laboratory).
  • Significantly impaired renal function as determined by a derived glomerular filtration rate (using the Modification of Diet in Renal Disease formula) of less than or equal to 30 mL/min/1.73 m2 calculated by the central laboratory.
  • Hypo- or hypercalcemia based on the central laboratory reference ranges for albumin-adjusted serum calcium.
  • Known to have tested positive for human immunodeficiency virus, hepatitis C virus, hepatitis B surface antigen or cirrhosis of the liver.
  • Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma) within the last 5 years.
  • Any metabolic bone disease, eg osteomalacia, osteogenesis imperfecta, rheumatoid arthritis, Paget's disease, Cushing's disease or, hyperprolactinemia which may interfere with the interpretation of the findings OR evidence of malabsorption syndromes which might interfere with absorption of vitamin D.
  • Received any solid organ or bone marrow transplant or is on chronic immunosuppression for any reason.
  • Any laboratory abnormality, which in the opinion of the investigator or Amgen, will prevent the subject from completing the study or interfere with the interpretation of the study results.
  • Administration of intravenous bisphosphonate, or fluoride (except for dental treatment) or strontium ranelate.
  • Oral bisphosphonate treatment:
  • greater than or equal to 3 months cumulatively in the past 2 years, OR
  • greater than or equal to 1 month in the past year, OR
  • Any use during the 3-month period prior to randomization
  • Administration of any of the following treatments 3 months prior to screening:
  • Anabolic steroids or testosterone
  • Glucocorticosteroids (greater than or equal to 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of greater than or equal to 50 mg)
  • Calcitonin
  • Calcitriol or vitamin D derivatives [vitamin D contained in supplements or multivitamins is allowed]
  • Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin
  • Chronic systemic ketoconazole, adrenocorticotrophic hormone (ACTH), cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists.
  • Androgen deprivation therapy
  • Known sensitivity to mammalian cell derived drug products.
  • Known intolerance to calcium or vitamin D supplements.
  • Height, weight or girth which may preclude accurate DXA measurements.
  • Bilateral hip replacements
  • Any physical or psychiatric disorder which, in the opinion of the investigator or Amgen, will prevent the subject from completing the study or interfere with the interpretation of the study results.
  • Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding of or completion of the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00980174

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

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00980174     History of Changes
Other Study ID Numbers: 20080098
Study First Received: September 17, 2009
Results First Received: October 31, 2012
Last Updated: January 22, 2013
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada
Denmark: Central Ethics Committee
Denmark: Danish Medicines Agency
Denmark: Laegemiddelstyrelsen
Denmark: Ministry of Health
EU: CHMP
European Union: European Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Ministry of Health
Poland: Drug Institut
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Sweden: Central Ethics Committee
Sweden: Lakemedelsverket
Sweden: Medical Products Agency
United States: Food and Drug Administration

Keywords provided by Amgen:
men
male
denosumab
BMD
lumbar spine
ADAMO
The ADAMO Trial
male osteoporosis
osteoporosis in men
males with low bone mineral density

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

ClinicalTrials.gov processed this record on April 20, 2014