Osteoporosis, Postmenopausal
Conditions
Keywords
India, dual energy x-ray absorptiometry, bone mineral density, denosumab
Brief summary
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.
Interventions
DRUGdenosumab
60mg subcutaneous injection, single dose
DRUGplacebo
placebo subcutaneous injection, single dose
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 6 | Baseline and 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline; 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. |
| Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) | From Baseline up to Month 6 | 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. |
| Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | Baseline; 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. |
| Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | 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. |
| Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6 | Baseline and 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. |
| Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6 | Baseline and 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. |
| Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Baseline and 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. |
| Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Baseline and 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. |
| Mean Percent Change From Baseline in BMD at the Total Hip, Femoral Neck, and Trochanter at Month 6 | Baseline and 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). |
| 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 | Baseline and 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. |
| Change From Baseline in Hematocrit at Month 6 | Baseline and 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. |
| Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 | Baseline and 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. |
| Change From Baseline in Mean Corpuscular Volume at Month 6 | Baseline and 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. |
| Change From Baseline in Red Blood Cell Count at Month 6 | Baseline and 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. |
| Change From Baseline in Red Cell Distribution Width at Month 6 | Baseline and 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. |
| Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 6 | 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. |
| Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Baseline and 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. |
Countries
India
Participant flow
Pre-assignment details
The study consisted of a Screening Phase of up to 2.5 months and a 6-month Double-blind Treatment Phase. A total of 551 participants (par.) were screened; 303 par. were screen failures, and 250 par. were randomized (2 par. were considered to be screen failures; however, these par. were randomized, 1 to each treatment group).
Participants by arm
| Arm | Count |
|---|---|
| Denosumab 60 mg Participants received denosumab 60 milligrams (mg) administered as a single subcutaneous (SC) injection at the start of the Double-blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 international units \[IU\]). | 124 |
| Placebo Participants received placebo administered as a single subcutaneous injection at the start of the Double-blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). | 126 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 10 |
Baseline characteristics
| Characteristic | Denosumab 60 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 62.6 Years STANDARD_DEVIATION 5.1 | 62.6 Years STANDARD_DEVIATION 4.85 | 62.6 Years STANDARD_DEVIATION 4.96 |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 124 participants | 126 participants | 250 participants |
| Sex: Female, Male Female | 124 Participants | 126 Participants | 250 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 124 | 3 / 126 |
| serious Total, serious adverse events | 1 / 124 | 3 / 126 |
Outcome results
Primary
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).
Time frame: Baseline and Month 6
Population: Intent-to-Treat Efficacy (ITTE) Population: all randomized participants who received one dose of study medication, and who had a Baseline measure and at least one post-Baseline efficacy measure during the Double-blind Treatment Phase. Only participants with BMD values at both Baseline and Month 6 were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 60 mg | Mean Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 6 | 4.26 percent change | Standard Error 0.413 |
| Placebo | Mean Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 6 | 1.20 percent change | Standard Error 0.403 |
p-value: <0.000195% CI: [1.91, 4.19]ANCOVA
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6 | Albumin/globulin ratio | 0.025 ratio | Standard Deviation 0.1446 |
| Denosumab 60 mg | Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6 | BUN/creatinine ratio | -5.896 ratio | Standard Deviation 18.0195 |
| Placebo | Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6 | Albumin/globulin ratio | 0.018 ratio | Standard Deviation 0.1518 |
| Placebo | Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6 | BUN/creatinine ratio | -1.860 ratio | Standard Deviation 19.84 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects the entire ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6 | Albumin, n=106, 114 | 0.689 grams per liter (g/L) | Standard Deviation 2.447 |
| Denosumab 60 mg | Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6 | Mean corpuscle hemoglobin conc., n=106, 107 | 2.321 grams per liter (g/L) | Standard Deviation 9.8653 |
| Denosumab 60 mg | Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6 | Hemoglobin, n=106, 107 | 2.236 grams per liter (g/L) | Standard Deviation 6.2891 |
| Denosumab 60 mg | Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6 | Total protein, n=106, 114 | 0.585 grams per liter (g/L) | Standard Deviation 3.8219 |
| Placebo | Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6 | Hemoglobin, n=106, 107 | 1.925 grams per liter (g/L) | Standard Deviation 8.4927 |
| Placebo | Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6 | Albumin, n=106, 114 | 0.746 grams per liter (g/L) | Standard Deviation 2.902 |
| Placebo | Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6 | Total protein, n=106, 114 | 0.886 grams per liter (g/L) | Standard Deviation 4.1621 |
| Placebo | Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6 | Mean corpuscle hemoglobin conc., n=106, 107 | 1.607 grams per liter (g/L) | Standard Deviation 10.0196 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects the entire ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Alkaline phosphatase, n=106, 114 | -18.179 International units per liter (IU/L) | Standard Deviation 25.0207 |
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Alanine amino transferase, n=106, 114 | 2.481 International units per liter (IU/L) | Standard Deviation 10.2421 |
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Aspartate amino transferase, 106, 113 | 2.755 International units per liter (IU/L) | Standard Deviation 10.9465 |
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Creatinine kinase, n=106, 114 | 6.170 International units per liter (IU/L) | Standard Deviation 51.2968 |
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Gamma glutamyl transferase, n=106, 114 | 2.915 International units per liter (IU/L) | Standard Deviation 12.8346 |
| Denosumab 60 mg | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Lactate dehydrogenase, n=106, 113 | 2.764 International units per liter (IU/L) | Standard Deviation 25.2811 |
| Placebo | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Gamma glutamyl transferase, n=106, 114 | -0.754 International units per liter (IU/L) | Standard Deviation 13.8433 |
| Placebo | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Alkaline phosphatase, n=106, 114 | -3.684 International units per liter (IU/L) | Standard Deviation 41.442 |
| Placebo | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Creatinine kinase, n=106, 114 | 11.175 International units per liter (IU/L) | Standard Deviation 63.0331 |
| Placebo | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Alanine amino transferase, n=106, 114 | 0.035 International units per liter (IU/L) | Standard Deviation 15.664 |
| Placebo | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Lactate dehydrogenase, n=106, 113 | 0.434 International units per liter (IU/L) | Standard Deviation 36.7389 |
| Placebo | Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6 | Aspartate amino transferase, 106, 113 | -0.965 International units per liter (IU/L) | Standard Deviation 16.9226 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects the entire ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Basophils, n=104, 103 | 0.001 10^9 cells per liter (GI/L) | Standard Deviation 0.0221 |
| Denosumab 60 mg | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Eosinophils, n=104, 103 | -0.076 10^9 cells per liter (GI/L) | Standard Deviation 0.2794 |
| Denosumab 60 mg | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Lymphocytes, n=104, 103 | -0.065 10^9 cells per liter (GI/L) | Standard Deviation 0.6044 |
| Denosumab 60 mg | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Monocytes, n=104, 103 | 0.000 10^9 cells per liter (GI/L) | Standard Deviation 0.1204 |
| Denosumab 60 mg | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Segmented neutrophils, n=104, 103 | -0.290 10^9 cells per liter (GI/L) | Standard Deviation 1.6142 |
| Denosumab 60 mg | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Total neutrophils, n=104, 103 | -0.297 10^9 cells per liter (GI/L) | Standard Deviation 1.6099 |
| Denosumab 60 mg | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Platelet count, n=103, 105 | 3.117 10^9 cells per liter (GI/L) | Standard Deviation 38.5322 |
| Denosumab 60 mg | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | White blood cell count, n=104, 103 | -0.436 10^9 cells per liter (GI/L) | Standard Deviation 1.6614 |
| Placebo | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | White blood cell count, n=104, 103 | -0.160 10^9 cells per liter (GI/L) | Standard Deviation 1.7629 |
| Placebo | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Basophils, n=104, 103 | -0.001 10^9 cells per liter (GI/L) | Standard Deviation 0.0262 |
| Placebo | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Segmented neutrophils, n=104, 103 | -0.129 10^9 cells per liter (GI/L) | Standard Deviation 1.7405 |
| Placebo | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Eosinophils, n=104, 103 | -0.001 10^9 cells per liter (GI/L) | Standard Deviation 0.3414 |
| Placebo | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Platelet count, n=103, 105 | 7.533 10^9 cells per liter (GI/L) | Standard Deviation 36.5761 |
| Placebo | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Lymphocytes, n=104, 103 | -0.056 10^9 cells per liter (GI/L) | Standard Deviation 0.7476 |
| Placebo | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Total neutrophils, n=104, 103 | -0.135 10^9 cells per liter (GI/L) | Standard Deviation 1.7343 |
| Placebo | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Total Neutrophils, Platelet Count, and White Blood Cell Count Month 6 | Monocytes, n=104, 103 | 0.032 10^9 cells per liter (GI/L) | Standard Deviation 0.1727 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects the entire ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 60 mg | 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 | Glucose, n=106, 113 | -0.571 millimoles per liter (MMOL/L) | Standard Deviation 2.2401 |
| Denosumab 60 mg | 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 | Sodium, n=106, 114 | -0.472 millimoles per liter (MMOL/L) | Standard Deviation 2.2979 |
| Denosumab 60 mg | 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 | Chloride, n=106, 114 | -0.802 millimoles per liter (MMOL/L) | Standard Deviation 3.0376 |
| Denosumab 60 mg | 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 | Phosphorus inorganic, n=106, 114 | -0.052 millimoles per liter (MMOL/L) | Standard Deviation 0.2047 |
| Denosumab 60 mg | 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 | Potassium, n=106, 113 | 0.140 millimoles per liter (MMOL/L) | Standard Deviation 0.4581 |
| Denosumab 60 mg | 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 | Triglycerides, n=106, 114 | -0.305 millimoles per liter (MMOL/L) | Standard Deviation 0.7413 |
| Denosumab 60 mg | 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 | Calcium, n=106, 113 | 0.012 millimoles per liter (MMOL/L) | Standard Deviation 0.1194 |
| Denosumab 60 mg | 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 | Urea/BUN, n=106, 114 | -0.283 millimoles per liter (MMOL/L) | Standard Deviation 1.1423 |
| Denosumab 60 mg | 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 | Magnesium, n=106, 114 | 0.009 millimoles per liter (MMOL/L) | Standard Deviation 0.0718 |
| Denosumab 60 mg | 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 | VLDL cholesterol calculation, n=103, 109 | -0.131 millimoles per liter (MMOL/L) | Standard Deviation 0.3178 |
| Denosumab 60 mg | 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 | Calcium corrected, n=12, 24 | 0.015 millimoles per liter (MMOL/L) | Standard Deviation 0.0573 |
| Placebo | 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 | VLDL cholesterol calculation, n=103, 109 | -0.105 millimoles per liter (MMOL/L) | Standard Deviation 0.3504 |
| Placebo | 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 | Calcium corrected, n=12, 24 | 0.008 millimoles per liter (MMOL/L) | Standard Deviation 0.0755 |
| Placebo | 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 | Calcium, n=106, 113 | 0.033 millimoles per liter (MMOL/L) | Standard Deviation 0.1069 |
| Placebo | 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 | Chloride, n=106, 114 | -0.895 millimoles per liter (MMOL/L) | Standard Deviation 3.0552 |
| Placebo | 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 | Glucose, n=106, 113 | -0.303 millimoles per liter (MMOL/L) | Standard Deviation 2.6346 |
| Placebo | 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 | Potassium, n=106, 113 | 0.158 millimoles per liter (MMOL/L) | Standard Deviation 0.4118 |
| Placebo | 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 | Magnesium, n=106, 114 | 0.009 millimoles per liter (MMOL/L) | Standard Deviation 0.0614 |
| Placebo | 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 | Sodium, n=106, 114 | -0.395 millimoles per liter (MMOL/L) | Standard Deviation 2.5921 |
| Placebo | 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 | Phosphorus inorganic, n=106, 114 | -0.012 millimoles per liter (MMOL/L) | Standard Deviation 0.1674 |
| Placebo | 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 | Triglycerides, n=106, 114 | -0.263 millimoles per liter (MMOL/L) | Standard Deviation 0.8433 |
| Placebo | 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 | Urea/BUN, n=106, 114 | 0.114 millimoles per liter (MMOL/L) | Standard Deviation 2.2032 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects the entire ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Indirect bilirubin, n=105, 112 | 0.210 micromoles per liter (UMOL/L) | Standard Deviation 2.7305 |
| Denosumab 60 mg | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Creatinine, n=106, 114 | 2.337 micromoles per liter (UMOL/L) | Standard Deviation 11.8458 |
| Denosumab 60 mg | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Total bilirubin, n=106, 114 | 0.358 micromoles per liter (UMOL/L) | Standard Deviation 2.8659 |
| Denosumab 60 mg | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Uric acid, n=106, 114 | -2.642 micromoles per liter (UMOL/L) | Standard Deviation 60.6677 |
| Denosumab 60 mg | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Direct bilirubin, n=105, 112 | 0.152 micromoles per liter (UMOL/L) | Standard Deviation 1.1667 |
| Placebo | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Uric acid, n=106, 114 | -6.316 micromoles per liter (UMOL/L) | Standard Deviation 61.9058 |
| Placebo | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Direct bilirubin, n=105, 112 | 0.089 micromoles per liter (UMOL/L) | Standard Deviation 1.2122 |
| Placebo | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Indirect bilirubin, n=105, 112 | -0.054 micromoles per liter (UMOL/L) | Standard Deviation 2.205 |
| Placebo | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Total bilirubin, n=106, 114 | 0.000 micromoles per liter (UMOL/L) | Standard Deviation 2.2102 |
| Placebo | Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Month 6 | Creatinine, n=106, 114 | 3.041 micromoles per liter (UMOL/L) | Standard Deviation 13.1471 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Hematocrit at Month 6 | 0.004 proportion of RBCs in blood | Standard Deviation 0.0204 |
| Placebo | Change From Baseline in Hematocrit at Month 6 | 0.004 proportion of RBCs in blood | Standard Deviation 0.0264 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 | 0.407 picograms | Standard Deviation 0.8613 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 | 0.260 picograms | Standard Deviation 1.2787 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Mean Corpuscular Volume at Month 6 | 0.623 femtoliters | Standard Deviation 2.9775 |
| Placebo | Change From Baseline in Mean Corpuscular Volume at Month 6 | 0.327 femtoliters | Standard Deviation 3.5309 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Red Blood Cell Count at Month 6 | 0.016 10^12 cells per liter (TI/L) | Standard Deviation 0.2575 |
| Placebo | Change From Baseline in Red Blood Cell Count at Month 6 | 0.034 10^12 cells per liter (TI/L) | Standard Deviation 0.3034 |
Secondary
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.
Time frame: Baseline and Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab 60 mg | Change From Baseline in Red Cell Distribution Width at Month 6 | 0.065 percentage | Standard Deviation 1.2126 |
| Placebo | Change From Baseline in Red Cell Distribution Width at Month 6 | -0.121 percentage | Standard Deviation 1.2735 |
Secondary
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).
Time frame: Baseline and Month 6
Population: ITTE Population. Only participants with BMD values at both Baseline and Month 6 were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Denosumab 60 mg | Mean Percent Change From Baseline in BMD at the Total Hip, Femoral Neck, and Trochanter at Month 6 | Total Hip | 2.02 percent change | Standard Error 0.27 |
| Denosumab 60 mg | Mean Percent Change From Baseline in BMD at the Total Hip, Femoral Neck, and Trochanter at Month 6 | Femoral Neck | 2.69 percent change | Standard Error 0.407 |
| Denosumab 60 mg | Mean Percent Change From Baseline in BMD at the Total Hip, Femoral Neck, and Trochanter at Month 6 | Trochanter | 2.49 percent change | Standard Error 0.366 |
| Placebo | Mean Percent Change From Baseline in BMD at the Total Hip, Femoral Neck, and Trochanter at Month 6 | Total Hip | 0.32 percent change | Standard Error 0.271 |
| Placebo | Mean Percent Change From Baseline in BMD at the Total Hip, Femoral Neck, and Trochanter at Month 6 | Femoral Neck | 0.40 percent change | Standard Error 0.409 |
| Placebo | Mean Percent Change From Baseline in BMD at the Total Hip, Femoral Neck, and Trochanter at Month 6 | Trochanter | 0.69 percent change | Standard Error 0.368 |
Secondary
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.
Time frame: Baseline; Months 1, 3, and 6
Population: ITTE Population. Only participants with s-CTX and s-PINP values at both Baseline and Months 1, 3, and 6 were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points/for different parameters, so the overall number of participants analyzed reflects the entire ITTE Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Denosumab 60 mg | 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 | s-CTx, Month 1, n=112, 121 | -80.61 percent change |
| Denosumab 60 mg | 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 | s-CTx, Month 3, n=107, 113 | -82.43 percent change |
| Denosumab 60 mg | 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 | s-CTx, Month 6, n=105, 113 | -62.5 percent change |
| Denosumab 60 mg | 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 | s-PINP, Month 1, n=110, 120 | -34.55 percent change |
| Denosumab 60 mg | 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 | s-PINP, Month 3, n=107, 111 | -78.08 percent change |
| Denosumab 60 mg | 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 | s-PINP, Month 6, n=104, 113 | -63.41 percent change |
| Placebo | 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 | s-PINP, Month 3, n=107, 111 | -27.87 percent change |
| Placebo | 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 | s-CTx, Month 1, n=112, 121 | -17.01 percent change |
| Placebo | 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 | s-PINP, Month 1, n=110, 120 | -13.62 percent change |
| Placebo | 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 | s-CTx, Month 3, n=107, 113 | -18.97 percent change |
| Placebo | 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 | s-PINP, Month 6, n=104, 113 | -25.81 percent change |
| Placebo | 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 | s-CTx, Month 6, n=105, 113 | -28.82 percent change |
Secondary
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.
Time frame: Baseline; Months 1, 3, and 6
Population: ITT Population. Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points/for different parameters, so the overall number of participants analyzed reflects the entire ITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 1: High, n=122, 125 | 1 participants |
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 1: Low, n=122, 125 | 1 participants |
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 3: High, n=117, 120 | 2 participants |
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 3: Low, n=117, 120 | 0 participants |
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 6: Low, n=111, 114 | 0 participants |
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | SBP, Month 1: Low, n=122, 125 | 1 participants |
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | SBP, Month 3: High, n=117, 120 | 1 participants |
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | SBP, Month 3: Low, n=117, 120 | 1 participants |
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | SBP, Month 6: Low, n=111, 114 | 2 participants |
| Denosumab 60 mg | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | Heart Rate, Month 3: Low, n=117, 120 | 0 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | SBP, Month 3: Low, n=117, 120 | 3 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 1: High, n=122, 125 | 2 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | SBP, Month 1: Low, n=122, 125 | 2 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 1: Low, n=122, 125 | 4 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | Heart Rate, Month 3: Low, n=117, 120 | 1 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 3: High, n=117, 120 | 0 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | SBP, Month 3: High, n=117, 120 | 1 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 3: Low, n=117, 120 | 2 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | SBP, Month 6: Low, n=111, 114 | 3 participants |
| Placebo | Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6 | DBP, Month 6: Low, n=111, 114 | 3 participants |
Secondary
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.
Time frame: From Baseline up to Month 6
Population: ITT Population: all participants who received one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Denosumab 60 mg | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) | Any AE | 38 participants |
| Denosumab 60 mg | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) | Any SAE | 1 participants |
| Placebo | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) | Any AE | 47 participants |
| Placebo | Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) | Any SAE | 3 participants |
Secondary
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.
Time frame: Month 6
Population: ITT Population. Only participants available at the specified time point were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Denosumab 60 mg | Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 6 | Neutralizing antibodies, n=0, 0 | NA participants |
| Denosumab 60 mg | Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 6 | Binding antibodies, Positive, n=110, 114 | 0 participants |
| Denosumab 60 mg | Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 6 | Binding antibodies, Negative, n=110, 114 | 110 participants |
| Placebo | Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 6 | Neutralizing antibodies, n=0, 0 | NA participants |
| Placebo | Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 6 | Binding antibodies, Positive, n=110, 114 | 0 participants |
| Placebo | Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 6 | Binding antibodies, Negative, n=110, 114 | 114 participants |
Secondary
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.
Time frame: Month 6
Population: ITT Population. Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points/for different parameters, so the overall number of participants analyzed reflects the entire ITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Alkaline phosphatase: High, n=107, 114 | 0 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Aspartate aminotransferase: High, n=107, 113 | 1 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Creatinine: High, n=107, 114 | 1 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Glucose: Low, n=107, 114 | 1 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Hematocrit: Low, n=106, 111 | 1 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Hemoglobin: Low, n=106, 111 | 2 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Inorganic Phosphorus: High, n=107, 114 | 0 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Potassium: High, n=107, 113 | 1 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Sodium: Low, n=107, 114 | 0 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Total Neutrophils: Low, n=104, 107 | 0 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Urea/BUN: High, n=107, 114 | 0 participants |
| Denosumab 60 mg | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Uric Acid: High, n=107, 114 | 0 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Urea/BUN: High, n=107, 114 | 1 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Alkaline phosphatase: High, n=107, 114 | 1 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Inorganic Phosphorus: High, n=107, 114 | 1 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Aspartate aminotransferase: High, n=107, 113 | 0 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Total Neutrophils: Low, n=104, 107 | 2 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Creatinine: High, n=107, 114 | 1 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Potassium: High, n=107, 113 | 0 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Glucose: Low, n=107, 114 | 0 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Uric Acid: High, n=107, 114 | 1 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Hematocrit: Low, n=106, 111 | 1 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Sodium: Low, n=107, 114 | 1 participants |
| Placebo | Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6 | Hemoglobin: Low, n=106, 111 | 3 participants |