Efficacy, Safety and Tolerability of Romosozumab in the Treatment of Japanese Women With Postmenopausal Osteoporosis

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01992159
• Collaborator: (none)
• Enrollment: 252
• Locations: 27
• Arms: 4
• Actual Duration (Months): 32.1
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if treatment with romosozumab increases bone mineral density in Japanese women with postmenopausal osteoporosis.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis (PMO)	Drug: Romosozumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 252 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multi-dose Phase 2 Study to Evaluate the Efficacy, Safety and Tolerability of Romosozumab in the Treatment of Japanese Women With Postmenopausal Osteoporosis
• Actual Study Start Date: Oct 12, 2012
• Actual Primary Completion Date: Oct 9, 2014
• Actual Study Completion Date: Jun 17, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Drug: Placebo; Administered by subcutaneous injection
Experimental: Romosozumab 70 mg Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 EVENITY™
Experimental: Romosozumab 140 mg Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 EVENITY™
Experimental: Romosozumab 210 mg Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 EVENITY™

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine [Baseline and 12 months]

   Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

Secondary Outcome Measures

1. Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine [Baseline and 6 months]

   Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

2. Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip [Baseline and 6 months]

   Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

3. Percent Change From Baseline to 12 Months in Bone Mineral Density at the Total Hip [Baseline and 12 months]

   Bone density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

4. Percent Change From Baseline to 6 Months in Bone Mineral Density at the Femoral Neck [Baseline and 6 months]

   Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

5. Percent Change From Baseline to 12 Months in Bone Mineral Density at the Femoral Neck [Baseline and 12 months]

   Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

6. Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) [Baseline, week 1, and months 1, 2, 3, 6, 9, and 12]

7. Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX) [Baseline, week 1, and months 1, 2, 3, 6, 9, and 12]

8. Percent Change From Baseline in Osteocalcin [Baseline, week 1, and months 1, 2, 3, 6, 9, and 12]

9. Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) [Baseline, week 1, and months 1, 2, 3, 6, 9, and 12]

10. Area Under the Curve Through Month 12 of P1NP [Baseline, week 1 and months 1, 2, 3, 6, 9, and 12.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Ambulatory, postmenopausal Japanese women with osteoporosis (defined as bone mineral density T-score of ≤ -4.00 at the lumbar spine or BMD T-score of ≤ -3.50 at the total hip, or femoral neck)

Exclusion Criteria:

• Severe osteoporosis

• Use of agents affecting bone metabolism

• History of metabolic or bone disease (except osteoporosis)

• Vitamin D insufficiency (vitamin D repletion and rescreening is permitted)

• Current hyper- or hypocalcemia

• Current, uncontrolled hyper- or hypothyroidism

• Current, uncontrolled hyper- or hypoparathyroidism

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Anjyo-shi	Aichi	Japan	446-0063
2	Research Site	Fukuoka-shi	Fukuoka	Japan	814-0165
3	Research Site	Kitakyushu-shi	Fukuoka	Japan	800-0057
4	Research Site	Yanagawa-shi	Fukuoka	Japan	832-0059
5	Research Site	Mizunami-shi	Gifu	Japan	509-6134
6	Research Site	Sapporo-shi	Hokkaido	Japan	063-0814
7	Research Site	Sapporo-shi	Hokkaido	Japan	065-0024
8	Research Site	Morioka-shi	Iwate	Japan	020-0066
9	Research Site	Yokohama-shi	Kanagawa	Japan	223-0062
10	Research Site	Yokohama-shi	Kanagawa	Japan	231-0861
11	Research Site	Kyoto-shi	Kyoto	Japan	602-8026
12	Research Site	Sendai-shi	Miyagi	Japan	981-3132
13	Research Site	Sendai-shi	Miyagi	Japan	983-0862
14	Research Site	Saito-shi	Miyazaki	Japan	881-0113
15	Research Site	Matsumoto-shi	Nagano	Japan	390-1401
16	Research Site	Ueda-shi	Nagano	Japan	386-0151
17	Research Site	Ueda-shi	Nagano	Japan	386-0405
18	Research Site	Osaka-shi	Osaka	Japan	559-0011
19	Research Site	Takatsuki-shi	Osaka	Japan	569-1123
20	Research Site	Kita-adachi-gun	Saitama	Japan	362-0806
21	Research Site	Hachioji-shi	Tokyo	Japan	192-0046
22	Research Site	Kiyose-shi	Tokyo	Japan	204-0021
23	Research Site	Minato-ku	Tokyo	Japan	108-0075
24	Research Site	Ota-ku	Tokyo	Japan	146-0094
25	Research Site	Shinagawa-ku	Tokyo	Japan	140-0011
26	Research Site	Suginami-ku	Tokyo	Japan	166-0003
27	Research Site	Toshima-ku	Tokyo	Japan	171-0033

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• Ishibashi H, Crittenden DB, Miyauchi A, Libanati C, Maddox J, Fan M, Chen L, Grauer A. Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: A phase 2 study. Bone. 2017 Oct;103:209-215. doi: 10.1016/j.bone.2017.07.005. Epub 2017 Jul 5.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01992159
• Other Study ID Numbers: 20101291
• First Posted: Nov 25, 2013
• Last Update Posted: Mar 25, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Amgen: Osteoporosis, Osteoporosis-Postmenopausal, Bone Diseases-Metabolic, Bone Diseases, Musculoskeletal Diseases
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal

Study Results

Participant Flow

Recruitment Details	This study was conducted at 24 centers in Japan. The first participant was enrolled on 12 October 2012 and the last participant enrolled on 15 October 2013.
Pre-assignment Detail	Participants were randomized in a 1:1:1:1 ratio to receive placebo or romosozumab 70, 140, or 210 mg subcutaneous (SC) injection every month (QM) for 12 months. Upon completion of the 12-month treatment period, participants were followed for another 3 months for assessment of antiromosozumab antibody formation (follow-up period).

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Period Title: Overall Study
STARTED	63	63	63	63
Received Treatment	63	63	63	63
Completed First 12 Months of Study	59	56	63	59
COMPLETED	59	55	62	59
NOT COMPLETED	4	8	1	4

Baseline Characteristics

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg	Total
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Total of all reporting groups
Overall Participants	63	63	63	63	252
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.8 (7.2)	66.5 (6.3)	68.4 (6.0)	68.3 (5.9)	67.7 (6.4)
Age, Customized (Count of Participants)
< 65 years	27 42.9%	30 47.6%	18 28.6%	18 28.6%	93 36.9%
≥ 65 to < 75 years	22 34.9%	22 34.9%	34 54%	34 54%	112 44.4%
≥ 75 years	14 22.2%	11 17.5%	11 17.5%	11 17.5%	47 18.7%
Sex: Female, Male (Count of Participants)
Female	63 100%	63 100%	63 100%	63 100%	252 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	63 100%	63 100%	63 100%	63 100%	252 100%
Lumbar Spine Bone Mineral Density (BMD) T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.69 (0.52)	-2.73 (0.57)	-2.65 (0.66)	-2.72 (0.42)	-2.70 (0.54)
Total Hip BMD T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.00 (0.60)	-1.97 (0.57)	-1.85 (0.68)	-1.95 (0.65)	-1.94 (0.63)
Femoral Neck BMD T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.31 (0.47)	-2.27 (0.53)	-2.28 (0.65)	-2.32 (0.59)	-2.29 (0.56)
Serum Procollagen Type 1 N-telopeptide (P1NP) (μg/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [μg/L]	52.4	51.9	47.6	50.9	50.5
Serum Type 1 Collagen C-telopeptide (CTX) (ng/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ng/L]	441.0	441.0	374.0	420.0	412.0
Osteocalcin (μg/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [μg/L]	22.17	22.50	21.01	22.75	22.03
Bone Specific Alkaline Phosphatase (BSAP) (μg/L) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [μg/L]	14.49	13.92	15.49	14.72	14.72

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine
Description	Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement (primary efficacy subset).

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Least Squares Mean (95% Confidence Interval) [percent change]	0.9	8.4	13.3	16.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 70 mg
	Comments	The primary analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-values were adjusted for multiplicity using a combination of a sequential test procedure and Hochberg's method to control type 1 error for the primary endpoint.
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	7.5
	Confidence Interval	(1-Sided) 95%; 6.5 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 140 mg
	Comments	The primary analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-values were adjusted for multiplicity using a combination of a sequential test procedure and Hochberg's method to control type 1 error for the primary endpoint.
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	12.4
	Confidence Interval	(1-Sided) 95%; 11.1 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments	The primary analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	One-sided p-values were adjusted for multiplicity using a combination of a sequential test procedure and Hochberg's method to control type 1 error for the primary endpoint.
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	16.0
	Confidence Interval	(1-Sided) 95%; 14.6 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine
Description	Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Least Squares Mean (95% Confidence Interval) [percent change]	1.2	6.5	10.2	13.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 70 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	5.3
	Confidence Interval	(1-Sided) 95%; 4.4 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 140 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	9.0
	Confidence Interval	(1-Sided) 95%; 8.0 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	11.9
	Confidence Interval	(1-Sided) 95%; 10.6 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip
Description	Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Least Squares Mean (95% Confidence Interval) [percent change]	0.6	1.2	2.3	3.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 70 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1250
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.6
	Confidence Interval	(1-Sided) 95%; -0.3 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 140 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	1.7
	Confidence Interval	(1-Sided) 95%; 0.9 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	2.6
	Confidence Interval	(1-Sided) 95%; 1.7 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From Baseline to 12 Months in Bone Mineral Density at the Total Hip
Description	Bone density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Least Squares Mean (95% Confidence Interval) [percent change]	0.6	2.1	3.2	4.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 70 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	1.5
	Confidence Interval	(1-Sided) 95%; 0.7 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 140 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	2.6
	Confidence Interval	(1-Sided) 95%; 1.8 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the total hip as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	4.1
	Confidence Interval	(1-Sided) 95%; 3.3 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percent Change From Baseline to 6 Months in Bone Mineral Density at the Femoral Neck
Description	Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Least Squares Mean (95% Confidence Interval) [percent change]	0.6	1.0	1.9	3.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 70 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2846
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	0.3
	Confidence Interval	(1-Sided) 95%; -0.6 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 140 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0151
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	1.3
	Confidence Interval	(1-Sided) 95%; 0.3 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	2.6
	Confidence Interval	(1-Sided) 95%; 1.5 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percent Change From Baseline to 12 Months in Bone Mineral Density at the Femoral Neck
Description	Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Least Squares Mean (95% Confidence Interval) [percent change]	0.3	1.9	2.9	3.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 70 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0067
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	1.6
	Confidence Interval	(1-Sided) 95%; 0.5 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 140 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	2.6
	Confidence Interval	(1-Sided) 95%; 1.6 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments	The analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the femoral neck as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	3.5
	Confidence Interval	(1-Sided) 95%; 2.3 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)
Time Frame	Baseline, week 1, and months 1, 2, 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, had at least 1 postbaseline measurement and with available data at each time point.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Week 1	-2.5 (9.0)	43.4 (24.0)	65.9 (25.7)	81.5 (34.6)
Month 1	-5.7 (22.1)	32.2 (22.9)	79.8 (41.7)	101.6 (41.1)
Month 2	-10.9 (18.5)	-0.7 (18.4)	34.6 (38.2)	59.8 (40.5)
Month 3	-11.5 (20.3)	-13.1 (18.3)	14.9 (32.2)	25.5 (33.4)
Month 6	-8.9 (23.3)	-16.8 (26.0)	-2.7 (28.0)	2.4 (24.8)
Month 9	-2.1 (32.0)	-16.9 (31.3)	-9.1 (30.9)	-4.0 (31.5)
Month 12	4.6 (37.9)	-11.1 (29.8)	-16.2 (27.4)	-13.1 (28.1)

8. Secondary Outcome

Title	Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)
Time Frame	Baseline, week 1, and months 1, 2, 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, had at least 1 postbaseline measurement, and with available data at each time point.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Week 1	11.9 (27.8)	-28.0 (25.8)	-32.1 (32.8)	-42.0 (25.4)
Month 1	14.9 (40.2)	-18.0 (34.3)	-8.0 (53.9)	-24.6 (30.5)
Month 2	14.1 (41.6)	-2.3 (48.4)	14.9 (67.8)	0.1 (49.1)
Month 3	16.1 (49.0)	-5.5 (48.3)	28.9 (84.1)	8.1 (53.8)
Month 6	13.6 (49.8)	-10.8 (52.2)	3.2 (71.8)	-13.4 (40.6)
Month 9	12.6 (56.6)	-13.2 (53.0)	-8.0 (55.7)	-15.3 (44.8)
Month 12	35.4 (81.7)	-4.1 (47.2)	2.1 (73.5)	-10.5 (53.8)

9. Secondary Outcome

Title	Percent Change From Baseline in Osteocalcin
Time Frame	Baseline, week 1, and months 1, 2, 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, had at least 1 postbaseline measurement, and with available data at each time point.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Week 1	2.6 (18.1)	6.5 (12.6)	7.9 (17.0)	5.5 (14.5)
Month 1	-3.8 (12.7)	26.5 (20.4)	51.2 (31.9)	66.4 (31.3)
Month 2	-7.0 (13.4)	13.7 (15.1)	39.3 (31.6)	48.9 (31.6)
Month 3	-7.2 (16.8)	4.9 (17.5)	28.4 (29.7)	27.5 (22.3)
Month 6	-10.3 (15.9)	-5.5 (18.8)	10.6 (24.7)	9.3 (19.2)
Month 9	-8.4 (18.2)	-6.8 (22.5)	-0.9 (24.0)	-1.3 (18.9)
Month 12	-6.8 (20.6)	-8.6 (21.8)	-9.4 (22.1)	-8.9 (17.9)

10. Secondary Outcome

Title	Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP)
Time Frame	Baseline, week 1, and months 1, 2, 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, had at least 1 postbaseline measurement, and with available data at each time point.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	55	62	59
Week 1	1.6 (13.4)	14.0 (14.5)	17.0 (16.4)	20.1 (17.9)
Month 1	-0.5 (22.1)	23.0 (19.9)	51.3 (27.6)	66.2 (31.9)
Month 2	-7.8 (16.9)	8.7 (20.8)	31.8 (27.9)	55.1 (31.0)
Month 3	-9.5 (16.3)	-2.8 (14.9)	23.5 (26.5)	39.6 (33.2)
Month 6	-6.6 (20.5)	-9.0 (19.0)	3.1 (21.6)	13.2 (26.8)
Month 9	-7.0 (20.5)	-10.7 (21.7)	-2.6 (25.3)	3.5 (23.8)
Month 12	-6.3 (22.7)	-13.2 (19.9)	-13.7 (23.3)	-9.3 (21.4)

11. Secondary Outcome

Title	Area Under the Curve Through Month 12 of P1NP
Time Frame	Baseline, week 1 and months 1, 2, 3, 6, 9, and 12.

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 10 doses of the assigned randomized treatment, had never received any dose of incorrect treatment, and had no missing P1NP measurements.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	59	54	62	58
Least Squares Mean (95% Confidence Interval) [ug*month/L]	554.5	539.2	638.5	708.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 70 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5084
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with the AUC of P1NP at month 12 as the dependent variable, and baseline P1NP and treatment (categorical) as the independent variables.
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	-15.3
	Confidence Interval	(2-Sided) 95%; -60.8 to 30.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with the AUC of P1NP at month 12 as the dependent variable, and baseline P1NP and treatment (categorical) as the independent variables.
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	84.1
	Confidence Interval	(2-Sided) 95%; 40.1 to 128.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model with the AUC of P1NP at months 12 as the dependent variable, and baseline P1NP and treatment (categorical) as the independent variables.
Method of Estimation	Estimation Parameter	Treatment Difference
	Estimated Value	153.8
	Confidence Interval	(2-Sided) 95%; 109.2 to 198.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	15 months
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Placebo		Romosozumab 70 mg		Romosozumab 140 mg		Romosozumab 210 mg
Arm/Group Description	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.		Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.		Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.		Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
All Cause Mortality
	Placebo		Romosozumab 70 mg		Romosozumab 140 mg		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Romosozumab 70 mg		Romosozumab 140 mg		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/63 (7.9%)		6/63 (9.5%)		3/63 (4.8%)		2/63 (3.2%)
Cardiac disorders
Acute myocardial infarction	0/63 (0%)		0/63 (0%)		1/63 (1.6%)		0/63 (0%)
Angina pectoris	1/63 (1.6%)		0/63 (0%)		0/63 (0%)		0/63 (0%)
Angina unstable	0/63 (0%)		0/63 (0%)		0/63 (0%)		1/63 (1.6%)
Atrioventricular block second degree	0/63 (0%)		1/63 (1.6%)		0/63 (0%)		0/63 (0%)
Coronary artery stenosis	0/63 (0%)		1/63 (1.6%)		0/63 (0%)		0/63 (0%)
Ventricular extrasystoles	1/63 (1.6%)		0/63 (0%)		0/63 (0%)		0/63 (0%)
Eye disorders
Cataract	0/63 (0%)		0/63 (0%)		0/63 (0%)		1/63 (1.6%)
Vitreous haemorrhage	0/63 (0%)		0/63 (0%)		0/63 (0%)		1/63 (1.6%)
Gastrointestinal disorders
Large intestine polyp	0/63 (0%)		0/63 (0%)		1/63 (1.6%)		0/63 (0%)
Hepatobiliary disorders
Cholelithiasis	0/63 (0%)		1/63 (1.6%)		0/63 (0%)		0/63 (0%)
Infections and infestations
Cellulitis	0/63 (0%)		1/63 (1.6%)		0/63 (0%)		0/63 (0%)
Injury, poisoning and procedural complications
Heat illness	1/63 (1.6%)		0/63 (0%)		0/63 (0%)		0/63 (0%)
Lumbar vertebral fracture	1/63 (1.6%)		0/63 (0%)		0/63 (0%)		0/63 (0%)
Meniscus injury	1/63 (1.6%)		0/63 (0%)		0/63 (0%)		0/63 (0%)
Post procedural haemorrhage	0/63 (0%)		0/63 (0%)		1/63 (1.6%)		0/63 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/63 (0%)		0/63 (0%)		0/63 (0%)		1/63 (1.6%)
Nervous system disorders
Cerebral infarction	0/63 (0%)		0/63 (0%)		1/63 (1.6%)		0/63 (0%)
Parkinson's disease	0/63 (0%)		1/63 (1.6%)		0/63 (0%)		0/63 (0%)
Subarachnoid haemorrhage	0/63 (0%)		1/63 (1.6%)		0/63 (0%)		0/63 (0%)
Psychiatric disorders
Depression	0/63 (0%)		1/63 (1.6%)		0/63 (0%)		0/63 (0%)
Reproductive system and breast disorders
Endometrial hypertrophy	1/63 (1.6%)		0/63 (0%)		0/63 (0%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Romosozumab 70 mg		Romosozumab 140 mg		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/63 (31.7%)		33/63 (52.4%)		29/63 (46%)		32/63 (50.8%)
Gastrointestinal disorders
Abdominal pain upper	4/63 (6.3%)		0/63 (0%)		1/63 (1.6%)		3/63 (4.8%)
Dental caries	1/63 (1.6%)		4/63 (6.3%)		3/63 (4.8%)		2/63 (3.2%)
Infections and infestations
Nasopharyngitis	8/63 (12.7%)		17/63 (27%)		17/63 (27%)		20/63 (31.7%)
Upper respiratory tract infection	2/63 (3.2%)		1/63 (1.6%)		4/63 (6.3%)		0/63 (0%)
Injury, poisoning and procedural complications
Contusion	5/63 (7.9%)		6/63 (9.5%)		2/63 (3.2%)		1/63 (1.6%)
Ligament sprain	4/63 (6.3%)		1/63 (1.6%)		0/63 (0%)		3/63 (4.8%)
Musculoskeletal and connective tissue disorders
Back pain	4/63 (6.3%)		2/63 (3.2%)		5/63 (7.9%)		3/63 (4.8%)
Osteoarthritis	1/63 (1.6%)		0/63 (0%)		2/63 (3.2%)		4/63 (6.3%)
Spinal osteoarthritis	0/63 (0%)		1/63 (1.6%)		1/63 (1.6%)		4/63 (6.3%)
Skin and subcutaneous tissue disorders
Dermatitis contact	1/63 (1.6%)		4/63 (6.3%)		1/63 (1.6%)		0/63 (0%)
Eczema	1/63 (1.6%)		4/63 (6.3%)		5/63 (7.9%)		1/63 (1.6%)
Vascular disorders
Hypertension	2/63 (3.2%)		1/63 (1.6%)		5/63 (7.9%)		1/63 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.