A Study in Indian 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 Indian postmenopausal women with osteoporosis.

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

Conditions
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Osteoporosis, Postmenopausal

Intervention / Treatment
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* Drug: denosumab
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory Indian postmenopausal women with osteoporosis greater than 5 years postmenopausal aged 55 to 75 years old absolute bone mineral density value consistent with a T-score less than -2.5 and greater than - 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 or equal to -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 interferes with interpretation of study results 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: 55 Years
Maximum Age: 75 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 treatment | Drug: denosumab<br>* 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 treatment | Drug: placebo<br>* placebo 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 Bone Mineral Density at the Lumbar Spine at Month 6 | Bone mineral density (BMD) at the lumbar spine was measured by the dual-energy x-ray absorptiometry (DXA) scanner. The mean percent change from Baseline in BMD was calculated as: (value at Month 6 minus Baseline value) * 100 / Baseline value. Analysis was performed using an Analysis of Covariance (ANCOVA) model with terms for treatment and baseline BMD at the lumbar spine (as a continuous covariate). | Baseline and Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change From Baseline in BMD at the Total Hip, Femoral Neck, and Trochanter at Month 6 | BMD at the total hip, femoral neck, and trochanter was measured by the DXA scanner. The mean percent change from Baseline in BMD was calculated as: (value at Month 6 minus Baseline value) * 100 / Baseline value. Analysis was performed using an ANCOVA model with terms for treatment and corresponding Baseline BMD (as a continuous covariate). | Baseline and Month 6 | 
| Median Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) and Serum Procollagen Type IN Propeptide (s-PINP) Markers at Months 1, 3, and 6 | Blood samples were collected for the measurement of s-CTx and s-PINP, which are used as biomarkers of bone resorption and formation, respectively. The median percent change from Baseline in s-CTX and s-PINP markers at Months 1, 3, and 6 was calculated as: (post-Baseline value minus Baseline value) * 100 / Baseline value. | Baseline; Months 1, 3, and 6 | 
| Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the 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 with hyperbilirubinaemia. Medical or scientific judgment was to have been exercised in other important medical events. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. | From Baseline up to Month 6 | 
| Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | Vital sign values of potential clinical concern were defined as: change in heart rate >30 beats per minutes (bpm), change in systolic blood pressure (SBP) >30 millimeters of mercury (mmHg), and change in diastolic blood pressure (DBP) >20 mmHg. The number of participants with post-Baseline vital sign values of potential clinical concern who did not have values of potential clinical concern at Baseline are summarized. If the change from Baseline is a decrease greater than the threshold, it is categorized as low. If the change from Baseline is an increase greater than the threshold, it is categorized ad high. | Baseline; Months 1, 3, and 6 | 
| Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | The number of participants with laboratory parameter values of potential clinical concern at Month 6 are summarized. The following are the laboratory values of potential clinical concern: alkaline phosphatase, High: >375 units/Liter (L); aspartate aminotransferase, High: >165 units/L; creatinine, High: >159 micromoles (µmol)/L; glucose, Low: <3 millimoles (mmol)/L; hematocrit, Low: <0.325; hemoglobin, Low: <91grams/L; phosphorus, High: >1.723 mmol/L; potassium, High: >6.3 mmol/L; sodium, Low: <130 mmol/L; total neutrophils, Low: <0.9 10^9 cells (GI)/L; blood urea nitrogen (BUN), High: >21mmol/L; uric acid, High: 654 µmol/L. | Month 6 | 
| Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6 | Blood samples were collected for the measurement of albumin/globulin ratio and BUN/creatinine ratio values. 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 Concentration (Conc.), and Total Protein at Month 6 | Blood samples were collected for the measurement of albumin, hemoglobin, mean corpuscle hemoglobin concentration, and total protein values. 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, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Blood samples were collected for the measurement of alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatinine kinase, gamma glutamyl transferase, and lactate dehydrogenase values. 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, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Blood samples were collected for the measurement of basophil, eosinophil, lymphocyte, monocyte, segmented neutrophil, total neutrophil, platelet count, and white blood cell count values. 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 | Blood samples were collected for the measurement of direct bilirubin, indirect bilirubin, total bilirubin, creatinine, and uric acid values. 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, and Very Low-density Lipoproteins (VLDL) Cholesterol Calculation at Month 6 | Blood samples were collected for the measurement of calcium corrected, calcium, chloride, glucose, potassium, magnesium, sodium, phosphorus inorganic, triglyceride, urea/BUN, and VLDL cholesterol calculation values. Change from Baseline was calcualted as the Month 6 value minus the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Hematocrit at Month 6 | Blood samples were collected for the measurement of hematocrit values. Change from Baseline was calculated as the Month 6 value minuse the Baseline value. | Baseline and Month 6 | 
| Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 | Blood samples were collected for the measurement of hemoglobin values. 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 | Blood samples were collected for the measurement of mean corpuscular volume values. 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 | Blood samples were collected for the measurement of red blood cell count values. 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 | Blood samples were collected for the measurement of red cell distribution width values. 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 at Month 6 | The number of participants with positive and negative results for both neutralizing antibodies to denosumab and for binding antibodies to denosumab at Month 6 are summarized. | Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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India, dual energy x-ray absorptiometry, bone mineral density, denosumab