Denosumab China Phase III Study

Exclusion Criteria

• •Bone/metabolic disease:
• •Any metabolic bone disease, e.g., osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings.
• •Paget's disease Cushing's disease Hyperprolactinemia
• •Current hyperparathyroidism or hypoparathyroidism by medical record
• •Thyroid condition: Hyperthyroidism or hypothyroidism. Only subjects with hypothyroidism who are on stable thyroid hormone replacement therapy may be allowed per the following criteria:
• •Rheumatoid arthritis
• •Malignancy:
• •Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5years.
• •Malabsorption syndrome: malabsorption syndrome or any gastrointestinal disorders associated with malabsorption, for example Crohn's Disease and chronic pancreatitis.
• •Renal disease - severe renal impairment
• •Liver disease:
• •Cirrhosis of the liver Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Chronic stable hepatitis B and C are acceptable if the subject otherwise meets study entry criteria (e.g., presence of hepatitis B surface antigen or positive Hepatitis C test result within 3 months of Screening).
• •Drug or alcohol abuse: Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding or completing the study.
• •Biological abnormalities:
• •Any disorder that compromises the ability of the subject to give written informed consent or to comply with study procedures.
• •Any physical or psychiatric disorder which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results.
• •Known to have tested positive for human immunodeficiency virus (HIV).
• •Vitamin D deficiency: Vitamin D deficiency (25-(OH) vitamin D level \<20 ng/mL). Vitamin D repletion will be permitted and after repletion subjects may be re-tested once for 25-(OH) vitamin D levels.
• •Oral/Dental Conditions Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw. Active dental or jaw condition which requires oral surgery. Planned invasive dental procedure. Non-healed dental or oral surgery.
• •Concomitant Medications:
• •Previous strontium or IV bisphosphonate: Administration of intravenous (IV) bisphosphonate, fluoride, or strontium for osteoporosis within the last 5 years.
• •Oral bisphosphonate: Oral bisphosphonate treatment for osteoporosis:
• •If used for ≥3 years cumulatively, subject is ineligible.
• •If used for \>3-months but \<3 years cumulatively:
• •If the last dose was \<1 year before enrolment, subject is ineligible. If the last dose was ≥1 year before enrolment, subject is eligible. If used ≤3 months, cumulatively, subject is eligible.
• •Bone metabolism drugs: Administration of any of the following treatments within the last 6 weeks:
• •Parathyroid hormone (PTH) or PTH derivatives, e.g., teriparatide. Anabolic steroids or testosterone. Glucocorticosteroids (\>5 mg prednisone equivalent per day for more than 10 days).
• •Systemic hormone replacement therapy. Selective estrogen receptor modulators (SERMs), e.g., raloxifene Tibolone. Calcitonin. Calcitriol or vitamin D derivatives. Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin.
• •Chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists.
• •Investigational drug exposure: Currently enrolled in an investigational device or drug trial(s) or it has not been at least 30 days since the last study visit in an investigational device or drug trial(s), or subject is receiving other investigational agent(s).
• •Sensitivity: Known sensitivity to mammalian cell-derived drug products.
• •Clinically significant hypersensitivity to denosumab Abnormal laboratory values
• •General: Any laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results.
• •Abnormal serum calcium: current hypocalcemia or hypercalcemia. Albumin adjusted serum calcium levels must be within normal limits of the central laboratory.
• •Liver transaminases:
• •Serum aspartate aminotransferase (AST) ≥2.0 x upper limits of normal (ULN). Serum alanine aminotransferase (ALT) ≥2.0 x ULN. Alkaline phosphatase and bilirubin ≥1.5 x ULN (isolated bilirubin ≥1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%.
• •DXA measurements:
• •Less than two lumbar vertebrae evaluable for DXA measurements. Height, weight, or girth which may preclude accurate DXA measurements.
• •Subjects with a history of greater than 2 vertebral fractures.
• •Subjects at very high risk of fracture who must be treated with active drugs in the opinion of investigator.