Postmenopausal osteoporosis /osteopenia
Conditions
Interventions
Product Name: Denosumab
Product Code: AMG 162
Pharmaceutical Form: Solution for injection
CAS Number: 615258-40-7
Current Sponsor code: AMG 162
Other descriptive name: Abgenix l-6 CHO OPG Ligand mAb l
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Postmenopausal, ambulatory women between 50 and 70 years old. • Postmenopausal will be defined as no vaginal bleeding or spotting for at least 12 months. • If the 12 months can not be confirmed (i.e.: hysterectomy), and if in the opinion of the investigator there is uncertainty regarding menopausal status, confirmation of serum FSH (= 50 mIU/mL) or serum estradiol (= 20 pg/mL) must be obtained. BMD values (g/cm2) at either the lumbar spine OR total hip as follows: • For lumbar spine, the BMD values (g/cm2) must be = 0.940 (GE Lunar) or = 0.827 (Hologic), OR • For total hip, the BMD values (g/cm2) must be = 0.756 (GE Lunar) or = 0.698 (Hologic) BMD values (g/cm2) at both the lumbar spine and total hip as follows: • For lumbar spine, BMD values (g/cm2) = 0.820 (GE Lunar) or = 0.717 (Hologic), AND • For total hip, BMD values (g/cm2) = 0.630 (GE Lunar) or = 0.576 (Hologic) First and second lumbar vertebrae (L1 and L2) evaluable for DXA and QCT measurements Ethical - Before any study-specific procedure, the appropriate written informed consent must be obtained Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures. -History of a fragility fracture (a fracture resulting from no or minor trauma, i.e. a fall from standing height or less) of the wrist, humerus, hip or pelvis after age 50 -Presence of moderate or severe vertebral deformity on VFA or lateral spine radiograph if VFA is not obtainable or evaluable. -Vitamin D deficiency [25(OH) vitamin D level < 12 ng/mL]. -Evidence of any of the following per subject report, chart review or central laboratory result: a) Uncontrolled hyper- or hypothyroidism b) Current hyper- or hypoparathyroidism c) Elevated transaminases d) Impaired renal function as determined by serum creatinine = 2.0 mg/dL e) Current hypo- or hypercalcemia determined by the central laboratory reference ranges for albumin adjusted serum calcium f) Active gastric or duodenal ulcer; history of significant gastrointestinal bleed requiring hospitalization or transfusion, or dyspepsia or gastroesophageal reflux disease that is uncontrolled by medication g) Rheumatoid arthritis, Paget’s disease, Cushing’s disease, hyperprolactinemia, or cirrhosis of the liver h) History of documented human immunodeficiency virus, hepatitis C virus, or hepatitis B i) Malignancy (except excised cutaneous basal cell, excised squamous cell carcinoma or excised cervical or breast ductal carcinoma in situ) within the last 5 years j) Any metabolic bone disease, e.g., osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of study results k) Malabsorption syndrome or any gastrointestinal disorders associated with malabsorption -Received any solid organ or bone marrow transplant. -Contraindicated or poorly tolerant of ALN therapy. -Known sensitivity to mammalian cell derived drug products. -Known intolerance to elemental calcium supplements. -Any history of intravenous bisphosphonate, fluoride (except for dental treatment) or strontium ranelate use. -Oral bisphosphonate treatment. a) = 3 months cumulatively, OR b) = 1 month cumulatively in the past year, OR c) Any use during the 3-month period prior to randomization -Treatment with PTH or PTH derivatives within the last year -Administration of any of the following treatments within 3 months of randomization: a) Any SERM (e.g., raloxifene) b) Tibolone c) Anabolic steroids or testosterone d) Glucocorticosteroids (= 5 mg prednisone equivalent per day for more than 10 days) e) Systemic (oral, transdermal, topical) hormone replacement therapy (local vaginal estrogen preparation will be allowed) f) Calcitonin g) Calcitriol or vitamin D derivatives h) Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin i) Chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists -Height, weight or girth which may preclude accurate DXA or QCT measurements. -Neither wrist evaluable by XtremeCT® (i.e., bilateral wrist replacement). -Neither hip evaluable by DXA and QCT (i.e., bilateral hip replacement or pins in both hips). -Presence of significant extremity tremor which, in the opinion of the investigator, would interfere with the XtremeCT® measurement. -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). -Any laboratory abnorm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to estimate the effect of denosumab (AMG 162), compared to placebo on cortical thickness at the distal radius, as determined by in-vivo microCT (XtremeCT®) at 12 months.;Primary end point(s): The primary efficacy endpoint is percent change in cortical thickness at the distal radius as determined by XtremeCT® from baseline to 12 months.;Secondary Objective: First four secondary objectives listed. Please see protocol (section 1.2) for remaining five secondary objectives. • Estimate the effect of denosumab, compared to placebo, on cortical thickness at the distal radius, as determined by XtremeCT® at 6 months • Estimate the effect of denosumab, compared to placebo, on cortical thickness at the distal tibia, as determined by in-vivo microCT (XtremeCT®) at 6 and 12 months • Estimate the effect of denosumab, compared to placebo, on cortical and trabecular volumetric bone density at the distal radius and the distal tibia, as determined by in-vivo XtremeCT® at 6 and 12 months • Estimate the effect of denosumab, compared to alendronate (ALN), on cortical and trabecular volumetric bone density and on cortical thickness at the distal radius and the distal tibia, as determined by XtremeCT® at 6 and 12 months | — |
Countries
Germany
Outcome results
None listed