Trial Outcomes & Findings for A Study to Evaluate the Effect of Romosozumab (AMG 785) on Bone Quality of the Forearm in Postmenopausal Women With Low Bone Mass (NCT NCT00950950)
NCT ID: NCT00950950
Last Updated: 2019-07-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Baseline and days 29, 57, 85, 127, and 169
Results posted on
2019-07-05
Participant Flow
This study was conducted at a single center in the United States.
Participants were equally randomized to receive romosozumab or placebo.
Participant milestones
| Measure |
Placebo
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
|
Overall Study
COMPLETED
|
11
|
11
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Placebo
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Study to Evaluate the Effect of Romosozumab (AMG 785) on Bone Quality of the Forearm in Postmenopausal Women With Low Bone Mass
Baseline characteristics by cohort
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.3 years
STANDARD_DEVIATION 5.6 • n=5 Participants
|
65.6 years
STANDARD_DEVIATION 7.2 • n=7 Participants
|
63.9 years
STANDARD_DEVIATION 6.5 • n=5 Participants
|
|
Age, Customized
18 - 64 years
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Customized
65 - 74 years
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Age, Customized
≥ 75 years
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Polar Moment of Inertia
|
1545.14 mm⁴
n=5 Participants
|
1496.50 mm⁴
n=7 Participants
|
1501.96 mm⁴
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius
Day 29
|
-1.16 percent change
Standard Error 1.40
|
0.16 percent change
Standard Error 0.95
|
|
Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius
Day 57
|
-1.03 percent change
Standard Error 1.00
|
-1.03 percent change
Standard Error 1.19
|
|
Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius
Day 85
|
-2.28 percent change
Standard Error 1.21
|
1.45 percent change
Standard Error 1.03
|
|
Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius
Day 127
|
-1.93 percent change
Standard Error 1.22
|
0.87 percent change
Standard Error 0.89
|
|
Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius
Day 169
|
-1.66 percent change
Standard Error 1.22
|
-0.08 percent change
Standard Error 1.12
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Total Bone Area at the Distal Radius
Day 85
|
-0.79 percent change
Standard Error 0.49
|
0.38 percent change
Standard Error 0.61
|
|
Percent Change From Baseline in Total Bone Area at the Distal Radius
Day 127
|
0.05 percent change
Standard Error 0.43
|
0.87 percent change
Standard Error 0.66
|
|
Percent Change From Baseline in Total Bone Area at the Distal Radius
Day 169
|
-0.23 percent change
Standard Error 0.46
|
-0.04 percent change
Standard Error 0.70
|
|
Percent Change From Baseline in Total Bone Area at the Distal Radius
Day 29
|
-0.07 percent change
Standard Error 0.56
|
-0.21 percent change
Standard Error 0.40
|
|
Percent Change From Baseline in Total Bone Area at the Distal Radius
Day 57
|
-0.08 percent change
Standard Error 0.48
|
-0.13 percent change
Standard Error 0.56
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius
Day 29
|
-0.39 percent change
Standard Error 0.40
|
-0.27 percent change
Standard Error 0.41
|
|
Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius
Day 57
|
-0.33 percent change
Standard Error 0.37
|
-0.49 percent change
Standard Error 0.27
|
|
Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius
Day 85
|
-0.86 percent change
Standard Error 0.47
|
-0.51 percent change
Standard Error 0.36
|
|
Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius
Day 127
|
-0.66 percent change
Standard Error 0.36
|
-0.43 percent change
Standard Error 0.37
|
|
Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius
Day 169
|
-1.34 percent change
Standard Error 0.30
|
-1.09 percent change
Standard Error 0.36
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius
Day 29
|
-0.30 percent change
Standard Error 0.48
|
-0.06 percent change
Standard Error 0.30
|
|
Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius
Day 57
|
-0.24 percent change
Standard Error 0.38
|
-0.34 percent change
Standard Error 0.44
|
|
Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius
Day 85
|
-0.07 percent change
Standard Error 0.19
|
-0.86 percent change
Standard Error 0.53
|
|
Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius
Day 127
|
-0.69 percent change
Standard Error 0.48
|
-1.26 percent change
Standard Error 0.53
|
|
Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius
Day 169
|
-0.10 percent change
Standard Error 0.42
|
-1.02 percent change
Standard Error 0.55
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Cortical Bone Area at the Distal Radius
Day 85
|
-1.39 percent change
Standard Error 0.77
|
0.69 percent change
Standard Error 0.67
|
|
Percent Change From Baseline in Cortical Bone Area at the Distal Radius
Day 127
|
-1.41 percent change
Standard Error 0.81
|
0.28 percent change
Standard Error 0.63
|
|
Percent Change From Baseline in Cortical Bone Area at the Distal Radius
Day 29
|
-0.27 percent change
Standard Error 0.58
|
0.06 percent change
Standard Error 0.63
|
|
Percent Change From Baseline in Cortical Bone Area at the Distal Radius
Day 57
|
-0.05 percent change
Standard Error 0.54
|
-0.53 percent change
Standard Error 0.64
|
|
Percent Change From Baseline in Cortical Bone Area at the Distal Radius
Day 169
|
-1.59 percent change
Standard Error 0.58
|
-0.50 percent change
Standard Error 0.74
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius
Day 57
|
-0.29 percent change
Standard Error 0.52
|
-0.86 percent change
Standard Error 0.45
|
|
Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius
Day 29
|
-0.33 percent change
Standard Error 0.57
|
0.07 percent change
Standard Error 0.46
|
|
Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius
Day 85
|
-1.08 percent change
Standard Error 0.66
|
-0.07 percent change
Standard Error 0.66
|
|
Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius
Day 127
|
-1.45 percent change
Standard Error 0.82
|
-0.66 percent change
Standard Error 0.57
|
|
Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius
Day 169
|
-1.69 percent change
Standard Error 0.55
|
-1.29 percent change
Standard Error 0.67
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius
Day 57
|
-0.24 percent change
Standard Error 0.21
|
-0.32 percent change
Standard Error 0.28
|
|
Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius
Day 29
|
-0.06 percent change
Standard Error 0.10
|
0.02 percent change
Standard Error 0.21
|
|
Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius
Day 85
|
0.32 percent change
Standard Error 0.24
|
-0.76 percent change
Standard Error 0.23
|
|
Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius
Day 127
|
-0.04 percent change
Standard Error 0.23
|
-0.92 percent change
Standard Error 0.40
|
|
Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius
Day 169
|
-0.10 percent change
Standard Error 0.23
|
-0.79 percent change
Standard Error 0.31
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Endocortical Circumference at the Distal Radius
Day 85
|
-0.03 percent change
Standard Error 0.39
|
-0.07 percent change
Standard Error 0.72
|
|
Percent Change From Baseline in Endocortical Circumference at the Distal Radius
Day 169
|
0.85 percent change
Standard Error 0.66
|
0.49 percent change
Standard Error 0.84
|
|
Percent Change From Baseline in Endocortical Circumference at the Distal Radius
Day 29
|
0.20 percent change
Standard Error 0.74
|
-0.19 percent change
Standard Error 0.50
|
|
Percent Change From Baseline in Endocortical Circumference at the Distal Radius
Day 57
|
-0.23 percent change
Standard Error 0.73
|
0.26 percent change
Standard Error 0.67
|
|
Percent Change From Baseline in Endocortical Circumference at the Distal Radius
Day 127
|
0.77 percent change
Standard Error 0.80
|
0.89 percent change
Standard Error 0.66
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Periosteal Circumference at the Distal Radius
Day 29
|
-0.04 percent change
Standard Error 0.28
|
-0.11 percent change
Standard Error 0.20
|
|
Percent Change From Baseline in Periosteal Circumference at the Distal Radius
Day 85
|
-0.40 percent change
Standard Error 0.25
|
0.19 percent change
Standard Error 0.31
|
|
Percent Change From Baseline in Periosteal Circumference at the Distal Radius
Day 127
|
0.02 percent change
Standard Error 0.22
|
0.43 percent change
Standard Error 0.33
|
|
Percent Change From Baseline in Periosteal Circumference at the Distal Radius
Day 169
|
-0.12 percent change
Standard Error 0.23
|
-0.02 percent change
Standard Error 0.35
|
|
Percent Change From Baseline in Periosteal Circumference at the Distal Radius
Day 57
|
-0.04 percent change
Standard Error 0.24
|
-0.07 percent change
Standard Error 0.28
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Cortical Thickness at the Distal Radius
Day 29
|
-0.29 percent change
Standard Error 0.82
|
0.22 percent change
Standard Error 0.77
|
|
Percent Change From Baseline in Cortical Thickness at the Distal Radius
Day 57
|
0.09 percent change
Standard Error 0.79
|
-0.56 percent change
Standard Error 0.85
|
|
Percent Change From Baseline in Cortical Thickness at the Distal Radius
Day 85
|
-1.14 percent change
Standard Error 0.72
|
0.64 percent change
Standard Error 0.99
|
|
Percent Change From Baseline in Cortical Thickness at the Distal Radius
Day 127
|
-1.69 percent change
Standard Error 1.14
|
-0.31 percent change
Standard Error 0.80
|
|
Percent Change From Baseline in Cortical Thickness at the Distal Radius
Day 169
|
-1.82 percent change
Standard Error 0.78
|
-0.62 percent change
Standard Error 1.09
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Polar Section Modulus at the Distal Radius
Day 29
|
0.18 percent change
Standard Error 0.78
|
0.02 percent change
Standard Error 0.78
|
|
Percent Change From Baseline in Polar Section Modulus at the Distal Radius
Day 57
|
-0.11 percent change
Standard Error 1.08
|
-0.46 percent change
Standard Error 1.05
|
|
Percent Change From Baseline in Polar Section Modulus at the Distal Radius
Day 85
|
-2.14 percent change
Standard Error 1.40
|
0.93 percent change
Standard Error 1.22
|
|
Percent Change From Baseline in Polar Section Modulus at the Distal Radius
Day 127
|
-2.31 percent change
Standard Error 1.55
|
1.76 percent change
Standard Error 1.32
|
|
Percent Change From Baseline in Polar Section Modulus at the Distal Radius
Day 169
|
-1.67 percent change
Standard Error 1.14
|
-1.05 percent change
Standard Error 1.20
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius
Day 29
|
-1.85 percent change
Standard Error 0.81
|
-0.78 percent change
Standard Error 0.51
|
|
Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius
Day 57
|
-1.32 percent change
Standard Error 0.75
|
-1.47 percent change
Standard Error 1.21
|
|
Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius
Day 85
|
0.36 percent change
Standard Error 0.99
|
-1.91 percent change
Standard Error 1.49
|
|
Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius
Day 127
|
-0.71 percent change
Standard Error 0.95
|
-1.57 percent change
Standard Error 0.94
|
|
Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius
Day 169
|
-0.41 percent change
Standard Error 0.98
|
-1.25 percent change
Standard Error 0.78
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius
Day 29
|
-0.22 percent change
Standard Error 0.91
|
-0.23 percent change
Standard Error 0.73
|
|
Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius
Day 57
|
-0.19 percent change
Standard Error 0.74
|
-0.49 percent change
Standard Error 0.88
|
|
Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius
Day 85
|
-1.90 percent change
Standard Error 1.09
|
0.94 percent change
Standard Error 0.83
|
|
Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius
Day 127
|
-0.90 percent change
Standard Error 0.65
|
1.41 percent change
Standard Error 1.04
|
|
Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius
Day 169
|
-1.25 percent change
Standard Error 0.75
|
-0.28 percent change
Standard Error 0.98
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Total Bone Area at the Ultradistal Radius
Day 29
|
-2.30 percent change
Standard Error 3.64
|
-0.72 percent change
Standard Error 2.35
|
|
Percent Change From Baseline in Total Bone Area at the Ultradistal Radius
Day 57
|
-5.11 percent change
Standard Error 2.44
|
-0.01 percent change
Standard Error 3.66
|
|
Percent Change From Baseline in Total Bone Area at the Ultradistal Radius
Day 85
|
-0.27 percent change
Standard Error 2.37
|
7.35 percent change
Standard Error 3.21
|
|
Percent Change From Baseline in Total Bone Area at the Ultradistal Radius
Day 127
|
-0.43 percent change
Standard Error 2.46
|
3.27 percent change
Standard Error 2.96
|
|
Percent Change From Baseline in Total Bone Area at the Ultradistal Radius
Day 169
|
1.90 percent change
Standard Error 2.50
|
0.91 percent change
Standard Error 3.32
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius
Day 57
|
0.13 percent change
Standard Error 0.53
|
-0.09 percent change
Standard Error 0.63
|
|
Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius
Day 29
|
0.63 percent change
Standard Error 0.43
|
-0.30 percent change
Standard Error 0.70
|
|
Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius
Day 85
|
0.63 percent change
Standard Error 0.56
|
1.16 percent change
Standard Error 0.39
|
|
Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius
Day 127
|
0.46 percent change
Standard Error 0.56
|
-0.14 percent change
Standard Error 0.46
|
|
Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius
Day 169
|
0.15 percent change
Standard Error 0.59
|
-0.64 percent change
Standard Error 0.97
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius
Day 57
|
6.22 percent change
Standard Error 3.19
|
1.19 percent change
Standard Error 2.98
|
|
Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius
Day 29
|
4.45 percent change
Standard Error 4.42
|
0.91 percent change
Standard Error 1.97
|
|
Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius
Day 85
|
1.52 percent change
Standard Error 2.64
|
-4.95 percent change
Standard Error 2.33
|
|
Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius
Day 127
|
1.43 percent change
Standard Error 2.35
|
-2.53 percent change
Standard Error 2.38
|
|
Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius
Day 169
|
-1.14 percent change
Standard Error 2.72
|
-0.81 percent change
Standard Error 2.59
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius
Day 169
|
2.84 percent change
Standard Error 4.18
|
1.57 percent change
Standard Error 5.20
|
|
Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius
Day 29
|
-3.54 percent change
Standard Error 5.68
|
-0.64 percent change
Standard Error 3.59
|
|
Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius
Day 57
|
-8.06 percent change
Standard Error 3.86
|
0.43 percent change
Standard Error 6.21
|
|
Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius
Day 85
|
-0.55 percent change
Standard Error 3.82
|
12.00 percent change
Standard Error 5.84
|
|
Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius
Day 127
|
-1.86 percent change
Standard Error 4.01
|
5.60 percent change
Standard Error 5.22
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius
Day 127
|
-0.70 percent change
Standard Error 6.15
|
5.68 percent change
Standard Error 6.54
|
|
Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius
Day 29
|
-3.26 percent change
Standard Error 7.35
|
-0.52 percent change
Standard Error 4.78
|
|
Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius
Day 57
|
-9.52 percent change
Standard Error 4.68
|
0.02 percent change
Standard Error 7.61
|
|
Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius
Day 85
|
1.02 percent change
Standard Error 5.51
|
14.64 percent change
Standard Error 7.06
|
|
Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius
Day 169
|
5.12 percent change
Standard Error 5.55
|
1.74 percent change
Standard Error 6.71
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius
Day 29
|
-0.78 percent change
Standard Error 1.88
|
-0.34 percent change
Standard Error 1.33
|
|
Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius
Day 57
|
-1.98 percent change
Standard Error 1.16
|
-1.30 percent change
Standard Error 1.59
|
|
Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius
Day 85
|
0.98 percent change
Standard Error 1.64
|
2.00 percent change
Standard Error 0.88
|
|
Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius
Day 127
|
0.53 percent change
Standard Error 1.92
|
-0.49 percent change
Standard Error 1.19
|
|
Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius
Day 169
|
1.74 percent change
Standard Error 1.47
|
-0.51 percent change
Standard Error 1.64
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius
Day 85
|
1.08 percent change
Standard Error 1.71
|
-0.90 percent change
Standard Error 2.30
|
|
Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius
Day 127
|
-0.87 percent change
Standard Error 1.29
|
-0.89 percent change
Standard Error 1.95
|
|
Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius
Day 169
|
-0.25 percent change
Standard Error 1.61
|
-1.51 percent change
Standard Error 1.86
|
|
Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius
Day 29
|
2.69 percent change
Standard Error 2.36
|
-0.14 percent change
Standard Error 1.00
|
|
Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius
Day 57
|
2.28 percent change
Standard Error 1.47
|
1.28 percent change
Standard Error 2.06
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Bone Mineral Density at the One-third Radius
Day 29
|
1.715 percent change
Standard Error 0.808
|
1.210 percent change
Standard Error 0.814
|
|
Percent Change From Baseline in Bone Mineral Density at the One-third Radius
Day 57
|
0.832 percent change
Standard Error 1.155
|
-0.694 percent change
Standard Error 0.827
|
|
Percent Change From Baseline in Bone Mineral Density at the One-third Radius
Day 85
|
0.790 percent change
Standard Error 1.117
|
-1.941 percent change
Standard Error 0.986
|
|
Percent Change From Baseline in Bone Mineral Density at the One-third Radius
Day 127
|
-0.118 percent change
Standard Error 1.405
|
-0.439 percent change
Standard Error 1.346
|
|
Percent Change From Baseline in Bone Mineral Density at the One-third Radius
Day 169
|
1.866 percent change
Standard Error 0.905
|
-0.328 percent change
Standard Error 0.702
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, 85, 127, and 169Population: Treated participants with available data at each time point
Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Bone Mineral Density at the Total Wrist
Day 29
|
1.829 percent change
Standard Error 0.617
|
-0.555 percent change
Standard Error 0.428
|
|
Percent Change From Baseline in Bone Mineral Density at the Total Wrist
Day 57
|
0.940 percent change
Standard Error 1.081
|
-1.651 percent change
Standard Error 0.574
|
|
Percent Change From Baseline in Bone Mineral Density at the Total Wrist
Day 85
|
0.233 percent change
Standard Error 0.996
|
-1.690 percent change
Standard Error 0.733
|
|
Percent Change From Baseline in Bone Mineral Density at the Total Wrist
Day 127
|
0.001 percent change
Standard Error 1.081
|
-0.369 percent change
Standard Error 0.765
|
|
Percent Change From Baseline in Bone Mineral Density at the Total Wrist
Day 169
|
0.357 percent change
Standard Error 1.237
|
-0.649 percent change
Standard Error 0.522
|
SECONDARY outcome
Timeframe: Baseline and days 85 and 169Population: Treated participants with available data at each time point
Bone mineral density was assessed using dual energy x-ray absorptiometry (DXA). Scans were analyzed by a central reader.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Bone Mineral Density at the Total Lumbar Spine
Day 85
|
0.345 percent change
Standard Error 1.224
|
4.786 percent change
Standard Error 0.846
|
|
Percent Change From Baseline in Bone Mineral Density at the Total Lumbar Spine
Day 169
|
0.149 percent change
Standard Error 0.905
|
7.876 percent change
Standard Error 1.351
|
SECONDARY outcome
Timeframe: Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169Population: Treated participants with available data at each time point
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 29
|
-0.33 percent change
Standard Error 3.44
|
101.85 percent change
Standard Error 19.97
|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 57
|
-6.93 percent change
Standard Error 4.52
|
74.77 percent change
Standard Error 10.91
|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 169
|
20.85 percent change
Standard Error 10.44
|
33.80 percent change
Standard Error 13.64
|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 4
|
-4.40 percent change
Standard Error 6.13
|
36.37 percent change
Standard Error 10.02
|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 15
|
3.46 percent change
Standard Error 5.64
|
146.39 percent change
Standard Error 20.00
|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 62
|
0.27 percent change
Standard Error 9.20
|
92.22 percent change
Standard Error 14.71
|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 71
|
19.61 percent change
Standard Error 16.22
|
106.91 percent change
Standard Error 14.08
|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 85
|
23.83 percent change
Standard Error 17.11
|
67.85 percent change
Standard Error 19.11
|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 99
|
10.94 percent change
Standard Error 15.57
|
17.07 percent change
Standard Error 11.79
|
|
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Day 127
|
5.49 percent change
Standard Error 10.26
|
12.56 percent change
Standard Error 8.57
|
SECONDARY outcome
Timeframe: Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169Population: Treated participants with available data at each time point
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 Participants
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 4
|
6.62 percent change
Standard Error 4.33
|
-23.77 percent change
Standard Error 7.78
|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 15
|
-2.29 percent change
Standard Error 5.15
|
-33.10 percent change
Standard Error 8.85
|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 29
|
-3.19 percent change
Standard Error 8.83
|
-21.42 percent change
Standard Error 13.98
|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 57
|
7.87 percent change
Standard Error 6.49
|
7.26 percent change
Standard Error 16.28
|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 62
|
8.69 percent change
Standard Error 5.78
|
-12.67 percent change
Standard Error 15.15
|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 71
|
5.60 percent change
Standard Error 5.59
|
-14.72 percent change
Standard Error 13.84
|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 85
|
-3.00 percent change
Standard Error 7.94
|
4.85 percent change
Standard Error 19.28
|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 99
|
-9.14 percent change
Standard Error 8.17
|
14.29 percent change
Standard Error 23.73
|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 127
|
-10.00 percent change
Standard Error 8.91
|
6.32 percent change
Standard Error 16.60
|
|
Percent Change From Baseline in Serum C-Telopeptide (sCTX)
Day 169
|
-3.61 percent change
Standard Error 8.95
|
16.06 percent change
Standard Error 20.53
|
SECONDARY outcome
Timeframe: First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169Population: All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated
Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Time to Maximum Serum Concentration (Tmax) of Romosozumab
First dose
|
3.0 days
Interval 3.0 to 3.0
|
—
|
|
Time to Maximum Serum Concentration (Tmax) of Romosozumab
Last dose
|
5.0 days
Interval 5.0 to 14.0
|
—
|
SECONDARY outcome
Timeframe: First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169Population: All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated
Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Maximum Serum Concentration (Cmax) of Romosozumab
First dose
|
26.8 μg/mL
Standard Deviation 6.4
|
—
|
|
Maximum Serum Concentration (Cmax) of Romosozumab
Last dose
|
32.3 μg/mL
Standard Deviation 9.6
|
—
|
SECONDARY outcome
Timeframe: First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169Population: All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Area Under the Serum Concentration-time Curve From Time 0 to Tau (AUC0-28)
First dose
|
422 μg*day/mL
Standard Deviation 75
|
—
|
|
Area Under the Serum Concentration-time Curve From Time 0 to Tau (AUC0-28)
Last dose
|
501 μg*day/mL
Standard Deviation 179
|
—
|
SECONDARY outcome
Timeframe: Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169Population: All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated
Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Outcome measures
| Measure |
Placebo
n=11 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf)
|
590 μg*day/mL
Standard Deviation 240
|
—
|
SECONDARY outcome
Timeframe: Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169Population: All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated
Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Outcome measures
| Measure |
Placebo
n=11 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Apparent Clearance (CL/F) of Romosozumab
|
5.82 mL/day/kg
Standard Deviation 2.12
|
—
|
SECONDARY outcome
Timeframe: Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169Population: All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated
Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay. The lower limit of quantification (LLOQ) was 50 ng/mL.
Outcome measures
| Measure |
Placebo
n=11 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Terminal Half-life (t1/2,z) of Romosozumab
|
6.82 days
Standard Deviation 0.92
|
—
|
SECONDARY outcome
Timeframe: First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169Population: All participants who received romosozumab and for whom the pharmacokinetic parameter could be calculated
Accumulation ratio was calculated as the ratio of AUC0-28 after the last dose to AUC0-28 after the first dose.
Outcome measures
| Measure |
Placebo
n=11 Participants
Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Accumulation Ratio
|
1.15 ratio
Standard Deviation 0.27
|
—
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Romosozumab
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=12 participants at risk
Participants received matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 participants at risk
Participants received 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal ulcer haemorrhage
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Arthritis infective
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Cauda equina syndrome
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
Other adverse events
| Measure |
Placebo
n=12 participants at risk
Participants received matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
Romosozumab
n=12 participants at risk
Participants received 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.
|
|---|---|---|
|
General disorders
Oedema peripheral
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
16.7%
2/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Pyrexia
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Vessel puncture site haematoma
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Sinusitis
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Urinary tract infection
|
16.7%
2/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Injury, poisoning and procedural complications
Joint sprain
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Injury, poisoning and procedural complications
Procedural nausea
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Injury, poisoning and procedural complications
Scratch
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
3/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Jaw disorder
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
16.7%
2/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Dizziness postural
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Headache
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Migraine
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Gastrointestinal disorders
Abdominal distension
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Gastrointestinal disorders
Constipation
|
16.7%
2/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Gastrointestinal disorders
Dyspepsia
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Gastrointestinal disorders
Dysphagia
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Gastrointestinal disorders
Enteritis
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Chest pain
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Injection site discomfort
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Injection site reaction
|
16.7%
2/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Injection site swelling
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Nervous system disorders
Presyncope
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Reproductive system and breast disorders
Breast tenderness
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Vascular disorders
Hypertension
|
16.7%
2/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
16.7%
2/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.00%
0/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
8.3%
1/12 • 6 months
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER