A High-resolution Peripheral Quantitative Computed Tomography Study in Postmenopausal Women Previously Treated With Denosumab

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00890981
• Collaborator: (none)
• Enrollment: 79
• Arm: 1
• Duration (Months): 13

Study Details

Study Description

Brief Summary

To evaluate the combined effect of denosumab treatment and discontinuation on cortical thickness at the distal radius by High Resolution-Peripheral Quantitative Computed Tomography (HR-pQCT). Participants randomized to either denosumab or placebo in the 20050179 (NCT00293813) study who completed that study (ie, attended an end of study visit) can be included in this study. At least 12 months should have elapsed since the patient's 20050179 end of study visit.

Condition or Disease	Intervention/Treatment	Phase
Low Bone Mass; Low Bone Mineral Density; Osteoporosis; Postmenopausal Osteoporosis	Procedure: high-resolution peripheral quantitative computed tomography (HR-pQCT); Procedure: Dual energy X-ray absorptiometry (DXA); Biological: Denosumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A HR-pQCT Study in Postmenopausal Women Previously Treated With Denosumab
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Other: Arm 1 Participants who were randomized to either denosumab or placebo in Study 20050179 and at least 12 months had elapsed from their 20050179 end-of-study visit had dual energy X-ray absorptiometry (DXA) of the forearm and HR-pQCT of the tibia and radius on Day 1 of this study. No study drug was administered.

Procedure: high-resolution peripheral quantitative computed tomography (HR-pQCT); Bone densitometry and microarchitecture assessments of the distal radius and the distal tibia by HR-pQCT on Day 1.; Procedure: Dual energy X-ray absorptiometry (DXA); Bone densitometry assessments of the forearm by DXA on day 1.; Biological: Denosumab; Denosumab 60 mg subcutaneously every 6 months in the previous study; Drug: Placebo; Placebo to denosumab subcutaneously every 6 months in the previous study

Outcome Measures

Primary Outcome Measures

1. Percent Change From the Parent Study Baseline in Cortical Thickness at the Distal Radius by HR-pQCT [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change from the 20050179 Baseline in cortical thickness at the distal radius as determined by high-resolution peripheral quantitative computed tomography (HR-pQCT) at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.

Secondary Outcome Measures

1. Percent Change From the Parent Study Baseline in Total Bone Mineral Density (BMD) at the Distal Radius by HR-pQCT [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change from the 20050179 Baseline in total BMD at the distal radius as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.

2. Percent Change From the Parent Study Baseline in Cortical BMD at the Distal Radius by HR-pQCT [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change from the 20050179 Baseline in cortical BMD at the distal radius as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.

3. Percent Change From the Parent Study Baseline in Trabecular BMD at the Distal Radius by HR-pQCT [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change from the 20050179 Baseline in trabecular BMD at the distal radius as determined by HR-pQCT at an average of 32 months since last subcutaneous dose of denosumab or placebo in study 20050179.

4. Percent Change From the Parent Study Baseline in Cortical Thickness at the Distal Tibia by HR-pQCT [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change from the 20050179 Baseline in cortical thickness at the distal tibia as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.

5. Percent Change From the Parent Study Baseline in Total BMD at the Distal Tibia by HR-pQCT [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change from the 20050179 Baseline in total BMD at the distal tibia as determined by HR-pQCT at an average of 32 months since last subcutaneous dose of denosumab or placebo in study 20050179.

6. Percent Change From the Parent Study Baseline in Cortical BMD at the Distal Tibia by HR-pQCT [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change from the 20050179 Baseline in cortical BMD at the distal tibia as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.

7. Percent Change From the Parent Study Baseline in Trabecular BMD at the Distal Tibia by HR-pQCT [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change from the 20050179 Baseline in trabecular BMD at the distal tibia as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.

8. Percent Change of Distal 1/3 Radius BMD From the Parent Study Baseline by DXA [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change of distal 1/3 radius BMD from the 20050179 Baseline as determined by dual energy X-ray absorptiometry (DXA) at an average of 32 months since last subcutaneous dose of denosumab or placebo in study 20050179.

9. Percent Change of Ultradistal Radius BMD From the Parent Study Baseline by DXA [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

   Percent change of ultradistal radius BMD from the 20050179 Baseline as determined by DXA at an average of 32 months since last the subcutaneous dose of denosumab or placebo in study 20050179.

10. Percent Change of Total Radius BMD From the Parent Study Baseline by DXA [Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.]

    Percent change of total radius BMD from the 20050179 Baseline as determined by DXA at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.

11. Actual Value of Serum Type I C-telopeptide [Day 1]

    Actual value of Serum Type I C-telopeptide measured from blood samples taken on Day 1 (an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179).

12. Actual Value of Procollagen Type 1 N-terminal Peptide [Day 1]

    Actual value of Type 1 N-terminal Peptide as measured from blood samples taken on Day 1 (an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ambulatory, postmenopausal women

• Randomized to either denosumab or placebo in the 20050179 (NCT00293813) study and completed that study (ie, attended an end of study visit)

• At least 12 months have elapsed since their end of 20050179 study visit

• Provide signed informed consent

Exclusion Criteria:

• Subjects who failed to receive both doses of denosumab (or SQ [subcutaneous] placebo) during the 20050179 study

• Subjects who were randomized to the alendronate arm during the 20050179 study

• Subjects diagnosed with any of the following conditions following completion of the 20050179 study:

• Hyperthyroidism

• Hyperparathyroidism

• Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma)

• Any condition that required chronic (greater than three months cumulative and greater than 5 mg/day) glucocorticoid therapy

• Other diseases which affect bone metabolism

• Self-reported alcohol or drug abuse within the previous 12 months

• Any disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with study procedures

• Received any investigational product other than denosumab in two years before the screening visit.

• Received > 3 months (or equivalent) of osteoporosis treatment since having completed the 20050179 study.

• Current use of the following osteoporosis agents: bisphosphonates, calcitonin, fluoride, parathyroid hormone analogue, selective estrogen receptor modulators, systemic oral or transdermal estrogen (except vaginal preparations and estrogen creams which are acceptable), strontium or tibolone.

• Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s) (other than Amgen trial 20080287), or subject is receiving other investigational agent(s).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• concept.747 Treatment/discontinuation on wrist.Journal-004521;

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00890981
• Other Study ID Numbers: 20080747
• First Posted: Apr 30, 2009
• Last Update Posted: Apr 2, 2014
• Last Verified: Mar 1, 2014

• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Bone Diseases, Metabolic; Denosumab

Study Results

Participant Flow

Recruitment Details	The first subject enrolled on 14-JUL-2009. The last subject enrolled on 12-MAY-2010

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179 (NCT00293813). No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Period Title: Overall Study
STARTED	39	40
COMPLETED	39	40
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group	Total
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.	Total of all reporting groups
Overall Participants	39	40	79
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.9 (5.8)	63.4 (6.5)	63.7 (6.1)
Sex: Female, Male (Count of Participants)
Female	39 100%	40 100%	79 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Number [Participants]	39 100%	40 100%	79 100%
Months since last dose in 20050179 (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	32.1 (2.5)	32.2 (2.7)	32.1 (2.6)

Outcome Measures

1. Primary Outcome

Title	Percent Change From the Parent Study Baseline in Cortical Thickness at the Distal Radius by HR-pQCT
Description	Percent change from the 20050179 Baseline in cortical thickness at the distal radius as determined by high-resolution peripheral quantitative computed tomography (HR-pQCT) at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	37
Least Squares Mean (95% Confidence Interval) [Percent change]	-5.5	-1.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear, quadratic and cubic time terms with treatment-by-time interaction
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0766
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.7
	Confidence Interval	() 95%; -0.4 to 7.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From the Parent Study Baseline in Total Bone Mineral Density (BMD) at the Distal Radius by HR-pQCT
Description	Percent change from the 20050179 Baseline in total BMD at the distal radius as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	37
Least Squares Mean (95% Confidence Interval) [Percent change]	-1.2	0.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear time term but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1648
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.5
	Confidence Interval	() 95%; -0.6 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From the Parent Study Baseline in Cortical BMD at the Distal Radius by HR-pQCT
Description	Percent change from the 20050179 Baseline in cortical BMD at the distal radius as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	37
Least Squares Mean (95% Confidence Interval) [Percent change]	-1.0	-0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear, quadratic and cubic time terms but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0228
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.9
	Confidence Interval	() 95%; 0.1 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From the Parent Study Baseline in Trabecular BMD at the Distal Radius by HR-pQCT
Description	Percent change from the 20050179 Baseline in trabecular BMD at the distal radius as determined by HR-pQCT at an average of 32 months since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	37
Least Squares Mean (95% Confidence Interval) [Percent change]	5.1	5.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model includes linear, quadratic and cubic time terms but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6560
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.7
	Confidence Interval	() 95%; -2.5 to 4.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percent Change From the Parent Study Baseline in Cortical Thickness at the Distal Tibia by HR-pQCT
Description	Percent change from the 20050179 Baseline in cortical thickness at the distal tibia as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	40
Least Squares Mean (95% Confidence Interval) [Percent change]	-6.4	-4.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear time term but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0594
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.8
	Confidence Interval	() 95%; -0.1 to 3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percent Change From the Parent Study Baseline in Total BMD at the Distal Tibia by HR-pQCT
Description	Percent change from the 20050179 Baseline in total BMD at the distal tibia as determined by HR-pQCT at an average of 32 months since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	40
Least Squares Mean (95% Confidence Interval) [Percent change]	-1.6	1.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear time term but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0032
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.6
	Confidence Interval	() 95%; 0.9 to 4.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percent Change From the Parent Study Baseline in Cortical BMD at the Distal Tibia by HR-pQCT
Description	Percent change from the 20050179 Baseline in cortical BMD at the distal tibia as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	40
Least Squares Mean (95% Confidence Interval) [Percent change]	-1.0	-0.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear, quadratic and cubic time terms but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2897
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.4
	Confidence Interval	() 95%; -0.4 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percent Change From the Parent Study Baseline in Trabecular BMD at the Distal Tibia by HR-pQCT
Description	Percent change from the 20050179 Baseline in trabecular BMD at the distal tibia as determined by HR-pQCT at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	40
Least Squares Mean (95% Confidence Interval) [Percent change]	2.9	6.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear time term but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0067
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.9
	Confidence Interval	() 95%; 1.1 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percent Change of Distal 1/3 Radius BMD From the Parent Study Baseline by DXA
Description	Percent change of distal 1/3 radius BMD from the 20050179 Baseline as determined by dual energy X-ray absorptiometry (DXA) at an average of 32 months since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	40
Least Squares Mean (95% Confidence Interval) [Percent change]	-2.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear time term but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0184
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.1
	Confidence Interval	() 95%; 0.4 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percent Change of Ultradistal Radius BMD From the Parent Study Baseline by DXA
Description	Percent change of ultradistal radius BMD from the 20050179 Baseline as determined by DXA at an average of 32 months since last the subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	40
Least Squares Mean (95% Confidence Interval) [Percent change]	-3.5	-1.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear time term but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0911
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.6
	Confidence Interval	() 95%; -0.3 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percent Change of Total Radius BMD From the Parent Study Baseline by DXA
Description	Percent change of total radius BMD from the 20050179 Baseline as determined by DXA at an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame	Baseline of Study 20050179 and Day 1 of this study. Study 20050179 duration was up to 12 months and the median time since completion of Study 20050179 was 32 months.

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	40
Least Squares Mean (95% Confidence Interval) [Percent change]	-3.0	-0.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	An analysis of covariance model was fit with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear time term but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0035
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.1
	Confidence Interval	() 95%; 0.7 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Actual Value of Serum Type I C-telopeptide
Description	Actual value of Serum Type I C-telopeptide measured from blood samples taken on Day 1 (an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	40
Least Squares Mean (95% Confidence Interval) [ng/mL]	0.6	0.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	ANCOVA based on the log transformed actual values with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear time term but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0591
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of Denosumab to Placebo
	Estimated Value	1.1
	Confidence Interval	() 95%; 1.0 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Actual Value of Procollagen Type 1 N-terminal Peptide
Description	Actual value of Type 1 N-terminal Peptide as measured from blood samples taken on Day 1 (an average of 32 months since the last subcutaneous dose of denosumab or placebo in study 20050179).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Participants with observed data.

Arm/Group Title	Previous Placebo Treatment Group	Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.	Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
Measure Participants	39	40
Least Squares Mean (95% Confidence Interval) [µg/L]	49.8	58.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Previous Placebo Treatment Group, Previous Denosumab Treatment Group
	Comments	ANCOVA based on the log transformed actual values with main effects for randomized treatment in study 20050179, baseline value, time since last subcutaneous dose of denosumab or placebo in study 20050179 as a continuous variable, and the age stratification from 20050179. Model included linear time term but without treatment-by-time interaction.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0079
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of Denosumab to Placebo
	Estimated Value	1.2
	Confidence Interval	() 95%; 1.0 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	AEs (serious only) were collected after informed consent and through 30 days after the study procedures, maximum time on study was 44 days.
Adverse Event Reporting Description	Only Serious Adverse Events were collected for this study.
Arm/Group Title	Previous Placebo Treatment Group		Previous Denosumab Treatment Group
Arm/Group Description	Participants who had previously received placebo and completed Study 20050179. No study drug was administered during this study.		Participants who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.
All Cause Mortality
	Previous Placebo Treatment Group		Previous Denosumab Treatment Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Previous Placebo Treatment Group		Previous Denosumab Treatment Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Previous Placebo Treatment Group		Previous Denosumab Treatment Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

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.