| Criteria: |
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Inclusion Criteria:
- 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. 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, ACTH (adrenocorticotrophic hormone), 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. |