A Study in Korean Postmenopausal Women With Osteoporosis to Evaluate the Efficacy and Safety of Denosumab

Study Overview
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Brief Summary
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The purpose of this study is to determine if denosumab is effective in increasing bone mineral density at the lumbar spine in Korean postmenopausal women with osteoporosis.

Official Title
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A Six Month Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study With a Six Month Open-Label Extension to Evaluate the Efficacy and Safety of Denosumab in Korean Postmenopausal Women With Osteoporosis

Conditions
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Osteoporosis, Postmenopausal

Intervention / Treatment
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* Drug: denosumab
* Drug: placebo
* Drug: open-label denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory Korean postmenopausal women with osteoporosis greater than 5 years postmenopausal aged 60 to 90 years old absolute bone mineral density value consistent with a T-score less than -2.5 and greater than or equal to - 4.0 at the either the lumbar spine or total hip, as measured by dual energy x-ray absorptiometry. Subjects with a T-score less than -4.0 are at very high risk for fracture and will be excluded. Exclusion Criteria: previous or current metabolic bone disease, Paget's or Cushing's disease, or hyperprolactinemia current hypo- or hyperparathyroidism or hypo- or hyperthyroidism unless on stable thyroid replacement therapy and TSH level meets criteria rheumatoid arthritis cirrhosis of the liver or unstable liver disease or ALT or AST greater than or equal to 2.0 times the upper limit of normal, or alkaline phosphatase and bilirubin greater than or equal to 1.5 times the upper limit of normal medications used to treat osteoporosis, defined for type and duration of use, and including IV and oral bisphosphonates medications that affect bone metabolism including parathyroid hormone or derivatives; anabolic steroids or testosterone; glucocorticosteroids; systemic hormone replacement therapy; selective estrogen receptor modulators; tibolone, calcitonin, and calcitriol or vitamin D derivatives; other bone active drugs including anticonvulsives (but not benzodiazepines) and heparin; chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, and gonadotropin-releasing hormone agonists malignancy within 5 years except certain resected types malabsorption syndrome or gastrointestinal disorders associated with malabsorption abnormal calcium level vitamin D deficiency any laboratory abnormality that will prevent the subject from completing the study or interfere with interpretation of study results severe renal impairment or on dialysis impaired immune system or subject is taking immunosuppressants oral or dental conditions including current or past history of osteomyelitis or osteonecrosis of the jaw; active dental or jaw condition with requires oral surgery; planned invasive dental procedure; un-healed dental or oral surgery 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 that will prevent the subject from completing the study or interferes with study results known to have tested positive for HIV less than two lumbar vertebrae evaluable for DXA measurements height, weight, or girth that may preclude accurate DXA measurements drug or alcohol abuse within 12 months that interferes with understanding or completing the study known sensitivity to mammalian cell-derived drug products use of an investigational drug or device within 30 days of enrollment or currently receiving other investigational agent(s)

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>denosumab 60mg subcutaneous injection, single dose at the start of the 6-month double-blind phase | Drug: denosumab<br>* double-blind phase: 60mg subcutaneous injection, single dose<br>|
| Placebo Comparator: Arm 2<br>placebo subcutaneous injection, single dose at the start of the 6-month double-blind phase | Drug: placebo<br>* double-blind phase: placebo subcutaneous injection, single dose<br>|
| Experimental: Arm 3<br>open-label phase follows the double-blind phase, denosumab 60mg subcutaneous injection, single dose at the start of the 6-month open-label phase | Drug: open-label denosumab<br>* open-label phase: 60mg subcutaneous injection, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change From Baseline in Lumbar Spine BMD at Month 6 | Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using the Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 6 - measure at Baseline) divided by the measure at Baseline * 100. | Baseline and Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change From Baseline in Lumbar Spine BMD at Month 1 | Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 1 - measure at Baseline) divided by the measure at Baseline * 100. | Baseline and Month 1 | 
| Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 1 and Month 6 | Mean percent change from Baseline in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covarience (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 1/6 - measure at Baseline) divided by the measure at Baseline * 100. | Baseline, Month 1 and Month 6 | 
| Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Months 1, 3 and 6 | Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Baseline=(measure at post-Baseline - measure at Baseline) divided by measure at Baseline * 100. | Baseline, Months 1, 3 and 6 | 
| Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. | From Baseline up to Month 6 | 
| Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Calcium Corrected, Calcium, Chloride, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Triglycerides, Urea/BUN, Very Low Density Lipoproteins (VLDL) Cholesterol Calculation at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Hematocrit at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Mean Corpuscular Volume at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Red Blood Cell Count at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Red Cell Distribution Width at Month 6 | Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 6 | Vital Sign Changes from Baseline of potential clinical concern for Diastolic Blood Pressure (<50 or >120 Bits Per Minutes [bpm]), Systolic Blood Pressure (>170 Millimeters of Mercury [mmHg] or <100 mmHg) and Heart rate (>110 mmHg or <50 mmHg) are summarized. Change from Baseline was calculated as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab | Number of participants with positive and negative results for both neutralizing antibodies to denosumab, and for binding antibodies to denosumab at Month 6 was summarized. | Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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denosumab, Republic of Korea, dual energy x-ray absorptiometry