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The purpose of this study is to evaluate the effect of romosozumab on parameters of bone quality of the forearm using peripheral quantitative computed tomography (pQCT) following multiple subcutaneous dose administrations of romosozumab in postmenopausal women with low bone mass.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months. |
|
| Romosozumab | Experimental | Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Romosozumab | Drug | Administered by subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius | The polar moment of inertia is a geometric measurement used to predict bone quality, specifically the ability to resist torsion (twisting), and is highly correlated with fracture load at the distal radius. The polar cross-sectional moment of inertia was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Total Bone Area at the Distal Radius | Total bone area was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. |
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Inclusion Criteria:
Healthy females between 55 to 80 years of age
Postmenopausal females (based on medical history) defined as 12 continuous months of spontaneous amenorrhea
Low bone mineral density (BMD), defined as a BMD T-score between -1.0 and -2.5 at the lumbar spine (L1-L4) and/or femoral neck
Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in)
25-hydroxyvitamin D ≥ 20 ng/mL at screening
Willing and able to take ≥ 500 mg calcium and ≥ 400 IU (but ≤ 1,000 IU) vitamin D daily
Exclusion Criteria:
Osteoporosis, defined as a BMD T-score ≤ -2.5 at the lumbar spine or femoral neck
History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis
Diagnosed with any condition that will affect bone metabolism
Subjects with fewer than 2 evaluable vertebrae; metal in forearms bilaterally that would not allow for at least one evaluable forearm
Administration of the following medications within 6 months before study drug administration. This includes all routes of administration, for example intranasal and topical skin patches, unless otherwise noted:
Administration of daily, weekly, or monthly bisphosphonates (BP) unless meeting the following criteria:
Greatly differing levels of physical activity or constant levels of intense physical exercise during the 6 months before study drug administration
Known sensitivity to mammalian-derived drug preparations
Known to be hepatitis B surface antigen, hepatitis C virus or human Immunodeficiency virus (HIV) positive or a known diagnosis of acquired immunodeficiency syndrome (AIDS)
Any organic or psychiatric disorder, which, in the opinion of the investigator, poses a risk to subject safety and may prevent the subject from completing the study or interfere with the interpretation of the study results
Unavailable for follow-up assessment or any concerns for subject's compliance with the protocol procedures
Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent
History or evidence of a clinically significant disorder, condition or disease that, in the opinion of the Investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Clinically significant abnormality during the screening physical examination, electrocardiogram (ECG) or laboratory evaluation
Participation in another clinical study within 4 weeks of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known
Has donated or lost 400 mL or more of blood or plasma within 8 weeks of study drug administration
Previous AMG 785 exposure
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
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| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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Participants were equally randomized to receive romosozumab or placebo.
This study was conducted at a single center in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months. |
| FG001 | Romosozumab | Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All treated participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months. |
| BG001 | Romosozumab | Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius | The polar moment of inertia is a geometric measurement used to predict bone quality, specifically the ability to resist torsion (twisting), and is highly correlated with fracture load at the distal radius. The polar cross-sectional moment of inertia was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
|
6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal ulcer haemorrhage | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| ID | Term |
|---|---|
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C557282 | romosozumab |
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| Placebo | Drug | Administered by subcutaneous injection |
|
| Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius | Total bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius | Total bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Cortical Bone Area at the Distal Radius | Cortical bone area was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius | Cortical bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius | Cortical bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Endocortical Circumference at the Distal Radius | Endocortical circumference was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Periosteal Circumference at the Distal Radius | Periosteal circumference was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Cortical Thickness at the Distal Radius | Cortical thickness was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Polar Section Modulus at the Distal Radius | Polar section modulus is a measurement of bone strength and was derived from pQCT measurements. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius | The polar strength strain index is a measurement of bone strength and was derived from pQCT measurements. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius | Axial moment of inertia is an indicator of the ability of bone to resist bending, and was derived from pQCT measurements based on a circular ring model. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Total Bone Area at the Ultradistal Radius | Total bone area was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius | Total bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius | Total bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius | Trabecular bone area was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius | Trabecular bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius | Trabecular bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius | The polar strength strain index is a measurement of bone strength and was derived from pQCT measurements. The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Bone Mineral Density at the One-third Radius | Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Bone Mineral Density at the Total Wrist | Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader. | Baseline and days 29, 57, 85, 127, and 169 |
| Percent Change From Baseline in Bone Mineral Density at the Total Lumbar Spine | Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader. | Baseline and days 85 and 169 |
| Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169 |
| Percent Change From Baseline in Serum C-Telopeptide (sCTX) | Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169 |
| Time to Maximum Serum Concentration (Tmax) of Romosozumab | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
| Maximum Serum Concentration (Cmax) of Romosozumab | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
| Area Under the Serum Concentration-time Curve From Time 0 to Tau (AUC0-28) | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. The area under the serum drug concentration-time curve from time zero to tau (tau = 28 days) (AUC0-28) was calculated by the linear trapezoidal method. | First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
| Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
| Apparent Clearance (CL/F) of Romosozumab | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
| Terminal Half-life (t1/2,z) of Romosozumab | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
| Accumulation Ratio | Accumulation ratio was calculated as the ratio of AUC0-28 after the last dose to AUC0-28 after the first dose. | First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Polar Moment of Inertia | The polar moment of inertia is a geometric measurement used to predict bone quality, specifically the ability to resist torsion (twisting), and is highly correlated with fracture load at the distal radius. The polar cross-sectional moment of inertia was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. | Median | Full Range | mm⁴ |
|
| OG001 | Romosozumab | Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months. |
|
|
| Secondary | Percent Change From Baseline in Total Bone Area at the Distal Radius | Total bone area was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius | Total bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius | Total bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Cortical Bone Area at the Distal Radius | Cortical bone area was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius | Cortical bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius | Cortical bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Endocortical Circumference at the Distal Radius | Endocortical circumference was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Periosteal Circumference at the Distal Radius | Periosteal circumference was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Cortical Thickness at the Distal Radius | Cortical thickness was derived from pQCT measurements based on applying a circular ring model to the cortical shell. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Polar Section Modulus at the Distal Radius | Polar section modulus is a measurement of bone strength and was derived from pQCT measurements. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius | The polar strength strain index is a measurement of bone strength and was derived from pQCT measurements. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius | Axial moment of inertia is an indicator of the ability of bone to resist bending, and was derived from pQCT measurements based on a circular ring model. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Total Bone Area at the Ultradistal Radius | Total bone area was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius | Total bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius | Total bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius | Trabecular bone area was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius | Trabecular bone mineral content was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius | Trabecular bone mineral density was assessed using peripheral quantitative computed tomography (pQCT). The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius | The polar strength strain index is a measurement of bone strength and was derived from pQCT measurements. The ultradistal slice was acquired at 4% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Bone Mineral Density at the One-third Radius | Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Bone Mineral Density at the Total Wrist | Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 29, 57, 85, 127, and 169 |
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| Secondary | Percent Change From Baseline in Bone Mineral Density at the Total Lumbar Spine | Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader. | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 85 and 169 |
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| Secondary | Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169 |
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| Secondary | Percent Change From Baseline in Serum C-Telopeptide (sCTX) | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169 |
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| Secondary | Time to Maximum Serum Concentration (Tmax) of Romosozumab | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated | Posted | Median | Full Range | days | First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
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| Secondary | Maximum Serum Concentration (Cmax) of Romosozumab | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated | Posted | Mean | Standard Deviation | μg/mL | First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
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| Secondary | Area Under the Serum Concentration-time Curve From Time 0 to Tau (AUC0-28) | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. The area under the serum drug concentration-time curve from time zero to tau (tau = 28 days) (AUC0-28) was calculated by the linear trapezoidal method. | All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated | Posted | Mean | Standard Deviation | μg*day/mL | First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
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| Secondary | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated | Posted | Mean | Standard Deviation | μg*day/mL | Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
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| Secondary | Apparent Clearance (CL/F) of Romosozumab | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated | Posted | Mean | Standard Deviation | mL/day/kg | Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
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| Secondary | Terminal Half-life (t1/2,z) of Romosozumab | Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL. | All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated | Posted | Mean | Standard Deviation | days | Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
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| Secondary | Accumulation Ratio | Accumulation ratio was calculated as the ratio of AUC0-28 after the last dose to AUC0-28 after the first dose. | All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated | Posted | Mean | Standard Deviation | ratio | First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169 |
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| 1 |
| 12 |
| 10 |
| 12 |
| EG001 | Romosozumab | Participants received 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months. | 1 | 12 | 10 | 12 |
| Arthritis infective | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Cauda equina syndrome | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Enteritis | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Injection site discomfort | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Injection site swelling | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Anaemia postoperative | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Joint sprain | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Procedural nausea | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Scratch | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Thermal burn | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Jaw disorder | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Dizziness postural | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Breast tenderness | Reproductive system and breast disorders | MedDRA 17.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 17.0 | Systematic Assessment |
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| Thrombophlebitis superficial | Vascular disorders | MedDRA 17.0 | Systematic Assessment |
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The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
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| Day 15 |
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| Day 62 |
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| Day 71 |
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| Day 85 |
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| Day 99 |
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| Day 127 |
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| Day 169 |
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| Day 15 |
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| Day 29 |
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| Day 57 |
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| Day 62 |
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| Day 71 |
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| Day 85 |
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| Day 99 |
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| Day 127 |
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| Day 169 |
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