STRUCTURE: An Open-label Study to Evaluate the Effect of Treatment With Romosozumab or Teriparatide in Postmenopausal Women

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01796301
• Collaborator: (none)
• Enrollment: 436
• Locations: 50
• Arms: 2
• Actual Duration (Months): 27.4
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective of the study was to evaluate the effect of 12 months of treatment with romosozumab compared with teriparatide on total hip bone mineral density (BMD) in postmenopausal women with osteoporosis who were previously treated with bisphosphonate therapy.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: Romozosumab; Drug: Teriparatide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 436 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized, Teriparatide-controlled Study to Evaluate the Effect of Treatment With Romosozumab in Postmenopausal Women With Osteoporosis Previously Treated With Bisphosphonate Therapy
• Actual Study Start Date: Jan 31, 2013
• Actual Primary Completion Date: May 14, 2015
• Actual Study Completion Date: May 14, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Romosozumab Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Drug: Romozosumab; Administered by subcutaneous injection once a month.; Other Names: AMG 785
Active Comparator: Teriparatide Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Drug: Teriparatide; Administered by subcutaneous injection once a day.; Other Names: Forteo Forsteo

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline Through Month 12 in Total Hip Bone Mineral Density (BMD) [Baseline, month 6 and month 12]

   Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA). Percent change from baseline through month 12 is the average of the treatment effect at months 6 and 12.

Secondary Outcome Measures

1. Percent Change From Baseline in Total Hip BMD at Month 6 [Baseline and month 6]

   Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).

2. Percent Change From Baseline in Total Hip BMD at Month 12 [Baseline and month 12]

   Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).

3. Percent Change From Baseline in Cortical BMD by Quantitative Computed Tomography (QCT) at the Total Hip at Month 6 [Baseline and month 6]

   Cortical BMD was measured by quantitative computed tomography (QCT) at the total hip.

4. Percent Change From Baseline in Cortical BMD by QCT at the Total Hip at Month 12 [Baseline and month 12]

   Cortical BMD was measured by quantitative computed tomography (QCT) at the total hip.

5. Percent Change From Baseline in Integral BMD by QCT at the Total Hip at Month 6 [Baseline and month 6]

   Integral BMD was measured by quantitative computed tomography (QCT) at the total hip.

6. Percent Change From Baseline in Integral BMD by QCT at the Total Hip at Month 12 [Baseline and month 12]

   Integral BMD was measured by quantitative computed tomography (QCT) at the total hip.

7. Percent Change From Baseline in Estimated Strength at the Total Hip at Month 6 [Baseline and month 6]

   Total hip estimated strength was assessed by finite element analysis (FEA) of QCT scans.

8. Percent Change From Baseline in Estimated Strength at the Total Hip at Month 12 [Baseline and month 12]

   Total hip estimated strength was assessed by finite element analysis (FEA) of QCT scans.

9. Percent Change From Baseline in Total Hip Integral Bone Mineral Content (BMC) by QCT at Month 6 [Baseline and month 6]

   Total hip integral BMC was measured using quantitative computed tomography (QCT).

10. Percent Change From Baseline in Total Hip Integral Bone Mineral Content (BMC) by QCT at Month 12 [Baseline and month 12]

    Total hip integral BMC was measured using quantitative computed tomography (QCT).

11. Percent Change From Baseline in Femoral Neck BMD at Month 6 [Baseline and month 6]

    Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).

12. Percent Change From Baseline in Femoral Neck BMD at Month 12 [Baseline and month 12]

    Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).

13. Percent Change From Baseline in Lumbar Spine BMD at Month 6 [Baseline and month 6]

    Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).

14. Percent Change From Baseline in Lumbar Spine BMD at Month 12 [Baseline and month 12]

    Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 90 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Postmenopausal women, aged ≥ 55 to ≤ 90.

• Received oral bisphosphonate therapy for at least 3 years immediately prior to screening

• BMD T-score ≤ -2.50 at the lumbar spine, total hip or femoral neck

• History of nonvertebral fracture after age 50, or vertebral fracture.

Exclusion Criteria:

• Use of other agents affecting bone metabolism including Strontium ranelate, fluoride (for osteoporosis), odanacatib (MK-0822) or any other cathepsin K inhibitor, IV bisphosphonates, denosumab, teriparatide (TPTD) or any parathyroid hormone (PTH) analogs, Systemic oral or transdermal estrogen, selective estrogen receptor modulators (SERMs), activated vitamin D3, vitamin K2, calcitonin, tibolone, cinacalcet, systemic glucocorticosteroids:

• History of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of study results, such as sclerosteosis, Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome.

• Vitamin D insufficiency, defined as 25 (OH) vitamin D levels < 20 ng/mL, as determined by the central laboratory.

• Current hyper- or hypocalcemia

• Current, uncontrolled hyper- or hypothyroidism

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Gainesville	Georgia	United States	30501
2	Research Site	Bethesda	Maryland	United States	20817
3	Research Site	Boston	Massachusetts	United States	02114
4	Research Site	Boston	Massachusetts	United States	02131
5	Research Site	Detroit	Michigan	United States	48236
6	Research Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1012AAR
7	Research Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1128AAF
8	Research Site	Cordoba	Córdoba	Argentina	X5000BNB
9	Research Site	Genk		Belgium	3600
10	Research Site	Gent		Belgium	9000
11	Research Site	Leuven		Belgium	3000
12	Research Site	Liege 1		Belgium	4000
13	Research Site	Calgary	Alberta	Canada	T2N 4Z6
14	Research Site	Vancouver	British Columbia	Canada	V6H 3X8
15	Research Site	Toronto	Ontario	Canada	M5C 2T2
16	Research Site	Toronto	Ontario	Canada	M5G 2C4
17	Research Site	Quebec		Canada	G1V 3M7
18	Research Site	Medellin	Antioquia	Colombia
19	Research Site	Barranquilla	Atlántico	Colombia	08001000
20	Research Site	Brno		Czechia	602 00
21	Research Site	Ostrava 1		Czechia	702 00
22	Research Site	Plzen		Czechia	305 99
23	Research Site	Praha 11 - Chodov		Czechia	148 00
24	Research Site	Uherske Hradiste		Czechia	686 01
25	Research Site	Aalborg		Denmark	9000
26	Research Site	Aarhus C		Denmark	8000
27	Research Site	Ballerup		Denmark	2750
28	Research Site	Esbjerg		Denmark	6700
29	Research Site	Hillerød		Denmark	3400
30	Research Site	Hvidovre		Denmark	2650
31	Research Site	Odense		Denmark	5000
32	Research Site	Budapest		Hungary	1036
33	Research Site	Budapest		Hungary	1083
34	Research Site	Budapest		Hungary	1123
35	Research Site	Gdynia		Poland	81-384
36	Research Site	Katowice		Poland	40-040
37	Research Site	Warszawa		Poland	01-192
38	Research Site	Wroclaw		Poland	50-088
39	Research Site	Granada	Andalucía	Spain	18012
40	Research Site	Barcelona	Cataluña	Spain	08041
41	Research Site	LHospitalet de Llobregat	Cataluña	Spain	08907
42	Research Site	Pozuelo de Alarcon	Madrid	Spain	28223
43	Research Site	Madrid		Spain	28041
44	Research Site	Madrid		Spain	28046
45	Research Site	Cardiff		United Kingdom	CF14 5GJ
46	Research Site	Chorley		United Kingdom	PR7 7NA
47	Research Site	Liverpool		United Kingdom	L22 0LG
48	Research Site	Northwood		United Kingdom	HA6 2RN
49	Research Site	Reading		United Kingdom	RG2 0TG
50	Research Site	Sidcup		United Kingdom	DA14 6LT

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01796301
• Other Study ID Numbers: 20080289; 2012-002948-24
• First Posted: Feb 21, 2013
• Last Update Posted: Nov 8, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Amgen: Postmenopausal Osteoporosis
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Teriparatide

Study Results

Participant Flow

Recruitment Details	The study was conducted at 46 sites in North America, Latin America, and Europe. Participants were enrolled from 31 January 2013 to 29 April 2014.
Pre-assignment Detail	A total of 777 subjects were screened for participation; 341 (43.9%) were excluded prior to randomization, primarily due to not meeting inclusion/exclusion criteria (306 [39.4%] subjects). A total of 436 participants were randomized into the study.

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Period Title: Overall Study
STARTED	218	218
Received Treatment	214	218
COMPLETED	200	198
NOT COMPLETED	18	20

Baseline Characteristics

Arm/Group Title	Teriparatide	Romosozumab	Total
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection 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	218	218	436
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.2 (7.7)	71.8 (7.4)	71.5 (7.5)
Age, Customized (Count of Participants)
< 65 years	48 22%	50 22.9%	98 22.5%
≥ 65 to < 75 years	96 44%	83 38.1%	179 41.1%
≥ 75 years	74 33.9%	85 39%	159 36.5%
Sex: Female, Male (Count of Participants)
Female	218 100%	218 100%	436 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	196 89.9%	191 87.6%	387 88.8%
Other	18 8.3%	23 10.6%	41 9.4%
American Indian or Alaska Native	1 0.5%	4 1.8%	5 1.1%
Asian	2 0.9%	0 0%	2 0.5%
Multiple	1 0.5%	0 0%	1 0.2%
Prior Fracture (Count of Participants)
Yes	217 99.5%	218 100%	435 99.8%
No	1 0.5%	0 0%	1 0.2%
Lumbar Spine BMD T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.87 (1.04)	-2.83 (1.10)	-2.85 (1.07)
Total Hip BMD T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.21 (0.72)	-2.27 (0.75)	-2.24 (0.74)
Femoral Neck BMD T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.43 (0.66)	-2.49 (0.67)	-2.46 (0.66)
Serum Type 1 Collagen C-telopeptide (sCTX) (ng/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/L]	260.1 (124.9)	252.3 (136.4)	256.2 (130.7)

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline Through Month 12 in Total Hip Bone Mineral Density (BMD)
Description	Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA). Percent change from baseline through month 12 is the average of the treatment effect at months 6 and 12.
Time Frame	Baseline, month 6 and month 12

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set includes randomized participants with a non-missing baseline and at least one post-baseline measurement.

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	209	206
Least Squares Mean (Standard Error) [percent change]	-0.6 (0.2)	2.6 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	The primary analysis to assess the treatment difference (Romosozumab - Teriparatide) employed a linear mixed effects model for repeated measures. The model included main effects for treatment group, visit (categorical), baseline sCTX, baseline hip DXA BMD value, machine type (categorical), and machine type-by-baseline value interaction (to adjust for the effect of machine type on baseline DXA BMD value) as fixed main effects using an unstructured within-subject variance-covariance structure.
	Type of Statistical Test	Superiority
	Comments	A two-step, step-down, fixed-sequential testing procedure was used to test the primary and key secondary efficacy endpoints for the comparison of romosozumab to teriparatide in the order presented for multiplicity adjustment to maintain the overall significance level at 0.05. The Key Secondary Efficacy Endpoints are the first 8 secondary endpoints reported below.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; 2.7 to 3.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in Total Hip BMD at Month 6
Description	Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 6

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	203	203
Least Squares Mean (Standard Error) [percent change]	-0.8 (0.2)	2.3 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, baseline BMD value, machine type, baseline BMD value-by machine type interaction, treatment-by-visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; 2.5 to 3.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline in Total Hip BMD at Month 12
Description	Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 12

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	202	197
Least Squares Mean (Standard Error) [percent change]	-0.5 (0.2)	2.9 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, baseline BMD value, machine type, baseline BMD value-by machine type interaction, treatment-by-visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; 2.8 to 4.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From Baseline in Cortical BMD by Quantitative Computed Tomography (QCT) at the Total Hip at Month 6
Description	Cortical BMD was measured by quantitative computed tomography (QCT) at the total hip.
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 6

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	156	163
Least Squares Mean (Standard Error) [percent change]	-2.7 (0.2)	0.7 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, parameter baseline value, treatment-by visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; 2.8 to 4.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

5. Secondary Outcome

Title	Percent Change From Baseline in Cortical BMD by QCT at the Total Hip at Month 12
Description	Cortical BMD was measured by quantitative computed tomography (QCT) at the total hip.
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 12

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	159	163
Least Squares Mean (Standard Error) [percent change]	-3.6 (0.3)	1.1 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, parameter baseline value, treatment-by visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; 3.9 to 5.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

6. Secondary Outcome

Title	Percent Change From Baseline in Integral BMD by QCT at the Total Hip at Month 6
Description	Integral BMD was measured by quantitative computed tomography (QCT) at the total hip.
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 6

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	156	163
Least Squares Mean (Standard Error) [percent change]	-0.8 (0.2)	2.3 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, parameter baseline value, treatment-by visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; 2.5 to 3.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

7. Secondary Outcome

Title	Percent Change From Baseline in Integral BMD by QCT at the Total Hip at Month 12
Description	Integral BMD was measured by quantitative computed tomography (QCT) at the total hip.
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 12

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	159	163
Least Squares Mean (Standard Error) [percent change]	-0.2 (0.2)	3.4 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, parameter baseline value, treatment-by visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; 2.9 to 4.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

8. Secondary Outcome

Title	Percent Change From Baseline in Estimated Strength at the Total Hip at Month 6
Description	Total hip estimated strength was assessed by finite element analysis (FEA) of QCT scans.
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 6

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	163	164
Least Squares Mean (Standard Error) [percent change]	-1.0 (0.2)	2.1 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, parameter baseline value, treatment-by visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; 2.4 to 3.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

9. Secondary Outcome

Title	Percent Change From Baseline in Estimated Strength at the Total Hip at Month 12
Description	Total hip estimated strength was assessed by finite element analysis (FEA) of QCT scans.
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 12

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	155	159
Least Squares Mean (Standard Error) [percent change]	-0.7 (0.4)	2.5 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, parameter baseline value, treatment-by visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; 2.1 to 4.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6
	Estimation Comments

10. Secondary Outcome

Title	Percent Change From Baseline in Total Hip Integral Bone Mineral Content (BMC) by QCT at Month 6
Description	Total hip integral BMC was measured using quantitative computed tomography (QCT).
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 6

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	156	163
Least Squares Mean (Standard Error) [percent change]	-0.7 (0.2)	2.4 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, parameter baseline value, treatment-by visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; 2.6 to 3.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

11. Secondary Outcome

Title	Percent Change From Baseline in Total Hip Integral Bone Mineral Content (BMC) by QCT at Month 12
Description	Total hip integral BMC was measured using quantitative computed tomography (QCT).
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 12

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	159	163
Least Squares Mean (Standard Error) [percent change]	0.0 (0.2)	3.6 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, parameter baseline value, treatment-by visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; 2.9 to 4.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

12. Secondary Outcome

Title	Percent Change From Baseline in Femoral Neck BMD at Month 6
Description	Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 6

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	203	203
Least Squares Mean (Standard Error) [percent change]	-1.1 (0.3)	2.1 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, baseline BMD value, machine type, baseline BMD value-by machine type interaction, treatment-by-visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; 2.5 to 3.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

13. Secondary Outcome

Title	Percent Change From Baseline in Femoral Neck BMD at Month 12
Description	Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 12

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	202	197
Least Squares Mean (Standard Error) [percent change]	-0.2 (0.3)	3.2 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, baseline BMD value, machine type, baseline BMD value-by machine type interaction, treatment-by-visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; 2.6 to 4.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

14. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine BMD at Month 6
Description	Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 6

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	204	203
Least Squares Mean (Standard Error) [percent change]	3.5 (0.3)	7.2 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, baseline BMD value, machine type, baseline BMD value-by machine type interaction, treatment-by-visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	3.8
	Confidence Interval	(2-Sided) 95%; 2.9 to 4.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

15. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine BMD at Month 12
Description	Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and month 12

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis set with values at baseline and month 12

Arm/Group Title	Teriparatide	Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
Measure Participants	201	197
Least Squares Mean (Standard Error) [percent change]	5.4 (0.4)	9.8 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Teriparatide, Romosozumab
	Comments	Treatment difference (Romosozumab - Teriparatide) was analyzed using a linear mixed effects model for repeated measures adjusting for treatment, visit, baseline serum type 1 collagen C-telopeptide value, baseline BMD value, machine type, baseline BMD value-by machine type interaction, treatment-by-visit interaction, and using an unstructured variance covariance structure.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Linear mixed effects repeated measures
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	4.4
	Confidence Interval	(2-Sided) 95%; 3.4 to 5.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Adverse Events

Time Frame	12 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	Teriparatide		Romosozumab
Arm/Group Description	Participants received 20 μg/day teriparatide administered by subcutaneous injection for 12 months.		Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
All Cause Mortality
	Teriparatide		Romosozumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Teriparatide		Romosozumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/214 (10.7%)		17/218 (7.8%)
Blood and lymphatic system disorders
Bone marrow failure	0/214 (0%)		1/218 (0.5%)
Cardiac disorders
Angina pectoris	0/214 (0%)		1/218 (0.5%)
Arrhythmia supraventricular	1/214 (0.5%)		0/218 (0%)
Atrial fibrillation	0/214 (0%)		2/218 (0.9%)
Bifascicular block	0/214 (0%)		1/218 (0.5%)
Bradycardia	0/214 (0%)		1/218 (0.5%)
Cardiac arrest	0/214 (0%)		1/218 (0.5%)
Cardiac failure chronic	0/214 (0%)		1/218 (0.5%)
Pericardial effusion	0/214 (0%)		1/218 (0.5%)
Sinus bradycardia	1/214 (0.5%)		0/218 (0%)
Ear and labyrinth disorders
Vertigo	1/214 (0.5%)		0/218 (0%)
Gastrointestinal disorders
Abdominal pain	2/214 (0.9%)		0/218 (0%)
Abdominal pain lower	0/214 (0%)		1/218 (0.5%)
Diarrhoea	1/214 (0.5%)		0/218 (0%)
Gastrointestinal haemorrhage	1/214 (0.5%)		0/218 (0%)
Large intestinal ulcer	1/214 (0.5%)		0/218 (0%)
Pancreatitis acute	0/214 (0%)		1/218 (0.5%)
Small intestinal obstruction	1/214 (0.5%)		0/218 (0%)
General disorders
Non-cardiac chest pain	0/214 (0%)		1/218 (0.5%)
Pyrexia	1/214 (0.5%)		0/218 (0%)
Hepatobiliary disorders
Cholelithiasis	1/214 (0.5%)		1/218 (0.5%)
Infections and infestations
Appendicitis	1/214 (0.5%)		0/218 (0%)
Diverticulitis	1/214 (0.5%)		0/218 (0%)
Influenza	0/214 (0%)		1/218 (0.5%)
Pneumonia	2/214 (0.9%)		1/218 (0.5%)
Pneumonia bacterial	1/214 (0.5%)		0/218 (0%)
Urinary tract infection fungal	0/214 (0%)		1/218 (0.5%)
Injury, poisoning and procedural complications
Femoral neck fracture	0/214 (0%)		1/218 (0.5%)
Muscle rupture	1/214 (0.5%)		0/218 (0%)
Procedural nausea	0/214 (0%)		1/218 (0.5%)
Radius fracture	1/214 (0.5%)		0/218 (0%)
Road traffic accident	1/214 (0.5%)		0/218 (0%)
Tibia fracture	1/214 (0.5%)		0/218 (0%)
Ulna fracture	0/214 (0%)		1/218 (0.5%)
Metabolism and nutrition disorders
Hyperglycaemia	0/214 (0%)		1/218 (0.5%)
Hypernatraemia	0/214 (0%)		1/218 (0.5%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/214 (0.5%)		1/218 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign soft tissue neoplasm	1/214 (0.5%)		0/218 (0%)
Colon adenoma	1/214 (0.5%)		0/218 (0%)
Keratoacanthoma	1/214 (0.5%)		0/218 (0%)
Lung adenocarcinoma	0/214 (0%)		1/218 (0.5%)
Myeloid leukaemia	0/214 (0%)		1/218 (0.5%)
Ovarian cancer stage III	0/214 (0%)		1/218 (0.5%)
Nervous system disorders
Cerebrovascular accident	0/214 (0%)		1/218 (0.5%)
Ischaemic stroke	0/214 (0%)		1/218 (0.5%)
Radicular pain	1/214 (0.5%)		0/218 (0%)
Radicular syndrome	0/214 (0%)		1/218 (0.5%)
Seizure	0/214 (0%)		1/218 (0.5%)
Syncope	1/214 (0.5%)		0/218 (0%)
Transient ischaemic attack	0/214 (0%)		1/218 (0.5%)
VIIth nerve paralysis	1/214 (0.5%)		0/218 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/214 (0%)		1/218 (0.5%)
Pleural effusion	0/214 (0%)		1/218 (0.5%)
Pulmonary fibrosis	1/214 (0.5%)		0/218 (0%)
Surgical and medical procedures
Medical device removal	0/214 (0%)		1/218 (0.5%)
Vascular disorders
Haemorrhage	0/214 (0%)		1/218 (0.5%)
Hypertension	0/214 (0%)		1/218 (0.5%)
Other (Not Including Serious) Adverse Events
	Teriparatide		Romosozumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/214 (35.5%)		79/218 (36.2%)
Infections and infestations
Nasopharyngitis	22/214 (10.3%)		28/218 (12.8%)
Upper respiratory tract infection	9/214 (4.2%)		11/218 (5%)
Injury, poisoning and procedural complications
Fall	5/214 (2.3%)		12/218 (5.5%)
Metabolism and nutrition disorders
Hypercalcaemia	22/214 (10.3%)		2/218 (0.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	13/214 (6.1%)		22/218 (10.1%)
Back pain	12/214 (5.6%)		19/218 (8.7%)
Musculoskeletal pain	5/214 (2.3%)		11/218 (5%)
Pain in extremity	4/214 (1.9%)		11/218 (5%)
Nervous system disorders
Headache	9/214 (4.2%)		14/218 (6.4%)

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.