Clinical Trial Summary : 20080747
A HR-pQCT Study in Postmenopausal Women Previously Treated with Denosumab FDA Regulated: None

This study has been completed.
Verified by Amgen, June 2011

Sponsored by: Amgen
Information provided by: Amgen
ClinicalTrials.gov Identifier: NCT00890981  

Purpose

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). Subjects randomized to either denosumab or placebo in the 20050179 study who completed that study (ie, the subject attended an end of study visit) can be included in this study. At least 12 months should have elapsed since the subject's 20050179 end of study visit


Condition Intervention Phase
Low Bone Mass
Low Bone Mineral Density
Osteoporosis
Postmenopausal Osteoporosis
Procedure/Surgery: HR-pQCT, DXA and BTM measurements
Phase 3

Study Type: Interventional
Study Design: Allocation: N/A
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A HR-pQCT Study in Postmenopausal Women Previously Treated with Denosumab


Further study details as provided by Amgen

Primary Outcome Measures:
  • Percent change from the parent study baseline in cortical thickness at the distal radius by HR-pQCT [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change from the 20050179 baseline in cortical thickness at the distal radius as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179

Secondary Outcome Measures:
  • Percent change from the parent study baseline in total BMD at the distal radius by HR-pQCT [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change from the 20050179 baseline in total BMD at the distal radius as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179

  • Percent change from the parent study baseline in cortical BMD at the distal radius by HR-pQCT [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change from the 20050179 baseline in cortical BMD at the distal radius as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.

  • Percent change from the parent study baseline in trabecular BMD at the distal radius by HR-pQCT [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change from the 20050179 baseline in trabecular BMD at the distal radius as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.

  • Percent change from the parent study baseline in cortical thickness at the distal tibia by HR-pQCT [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change from the 20050179 baseline in cortical thickness at the distal tibia as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.

  • Percent change from the parent study baseline in total BMD at the distal tibia by HR-pQCT [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change from the 20050179 baseline in total BMD at the distal tibia as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.

  • Percent change from the parent study baseline in cortical BMD at the distal tibia by HR-pQCT [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change from the 20050179 baseline in cortical BMD at the distal tibia as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.

  • Percent change from the parent study baseline in trabecular BMD at the distal tibia by HR-pQCT [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change from the 20050179 baseline in trabecular BMD at the distal tibia as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.

  • Percent change of distal 1/3 radius BMD from the parent study baseline by DXA [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change of distal 1/3 radius BMD from the 20050179 baseline as determined by DXA at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.

  • Percent change of ultradistal radius BMD from the parent study baseline by DXA [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change of ultradistal radius BMD from the 20050179 baseline as determined by DXA at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.

  • Percent change of total radius BMD from the parent study baseline by DXA [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Percent change of total radius BMD from the 20050179 baseline as determined by DXA at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.

  • Actual Value of Serum Type I C-telopeptide [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Actual value at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179

  • Actual Value of Procollagen Type 1 N-terminal Peptide [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Actual value at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179

Enrollment: 79
Study Start Date:June 2009 Study Start Date Type:

Study Completion Date: August 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Other: Arm 1
Procedure/Surgery: HR-pQCT, DXA and BTM measurements
Subjects who sign the informed consent will undergo HR-pQCT and DXA measurements. The study will consist of one visit for screening, enrollment and completion of study procedures (DXA, HR-pQCT and BTM). No study drug will be administered during the course of the study.


Eligibility

Genders Eligible for Study:  Female
Gender Based: 
Gender Eligibility Description: 
Accepts Healthy Volunteers:  No

Criteria

Inclusion Criteria:
• Ambulatory, postmenopausal women
• Randomized to either denosumab or placebo in the 20050179 study and completed that study (ie, the subject 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

Contacts
Contact: Amgen Call Center 866-572-6436

Sponsors and Collaborators
Amgen
Oversight
Is FDA Regulated Intervention: None
U.S. FDA IND/IDE Study: yes
Section 801 Trial: None
Unapproved/Uncleared Device: None

Investigators
Study Director: MD   Amgen Inc.

More Information
Responsible Party: Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier: NCT00890981
Other Study ID Numbers: 20080747
Health Authority: Argentina: Ministry of Health
Canada: Health Canada
United States: Food and Drug Administration
Argentina: ANMAT (Administracion Nacional de Medicamentos Alimentos y Tecnologia Medica)
U.S. FDA-regulated Drug
U.S. FDA-regulated Device
Post Prior to Approval/Clearance
Pediatric Postmarket Surveillance
Product Exported From U.S.
No Keywords provided

Study Results

  Participant Flow

 Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The first subject enrolled on 14-JUL-2009. The last subject enrolled on 12-MAY-2010

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Participant Flow:   Overall Study

  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
 STARTED  39 40
 COMPLETED  39 40
 NOT COMPLETED  0 0

  Baseline Characteristics

 Hide Baseline Characteristics

Reporting Groups
Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Baseline Measures
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group Total
Number of Participants
[units: Participants]
39 40 79
Age Categorical
[units: Participants]
     
<=18 years 0 0 0
Between 18 and 65 years 12 21 33
>=65 years 17 19 36
Age
[units: Years]
Mean ± Standard Deviation
63.9 ± 5.8 63.4 ± 6.5 63.7 ± 6.1
Gender
[units: Participants]
     
Female 39 40 79
Male 0 0 0
Race, Customized
[units: Participants]

White or Caucasian
39 40 79
Months since last SC dose of 20050179
[units: Months]
Mean ± Standard Deviation
32.1 ± 2.5 32.2 ± 2.7 32.1 ± 2.6
  Outcome Measures

 Hide All Outcome Measures


1. Primary:  Percent change from the parent study baseline in cortical thickness at the distal radius by HR-pQCT   [ Time Frame: Day 1 ]
Measure Type Primary
Measure Name Percent change from the parent study baseline in cortical thickness at the distal radius by HR-pQCT
Measure Description Percent change from the 20050179 baseline in cortical thickness at the distal radius as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 37
Percent change from the parent study baseline in cortical thickness at the distal radius by HR-pQCT
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
-5.5 (-8.3 to -2.8) -1.8 (-4.8 to 1.2)


Statistical Analysis 1 for Percent change from the parent study baseline in cortical thickness at the distal radius by HR-pQCT
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0766
Mean Difference (Final Values) [5] 3.7
95% Confidence Interval ( -0.4 to 7.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


2. Secondary:  Percent change from the parent study baseline in total BMD at the distal radius by HR-pQCT   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change from the parent study baseline in total BMD at the distal radius by HR-pQCT
Measure Description Percent change from the 20050179 baseline in total BMD at the distal radius as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 37
Percent change from the parent study baseline in total BMD at the distal radius by HR-pQCT
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
-1.2 (-2.6 to 0.2) 0.3 (-1.2 to 1.7)


Statistical Analysis 1 for Percent change from the parent study baseline in total BMD at the distal radius by HR-pQCT
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.1648
Mean Difference (Final Values) [5] 1.5
95% Confidence Interval ( -0.6 to 3.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


3. Secondary:  Percent change from the parent study baseline in cortical BMD at the distal radius by HR-pQCT   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change from the parent study baseline in cortical BMD at the distal radius by HR-pQCT
Measure Description Percent change from the 20050179 baseline in cortical BMD at the distal radius as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 37
Percent change from the parent study baseline in cortical BMD at the distal radius by HR-pQCT
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
-1.0 (-1.7 to -0.3) -0.0 (-0.8 to 0.8)


Statistical Analysis 1 for Percent change from the parent study baseline in cortical BMD at the distal radius by HR-pQCT
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0228
Mean Difference (Final Values) [5] 0.9
95% Confidence Interval ( 0.1 to 1.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


4. Secondary:  Percent change from the parent study baseline in trabecular BMD at the distal radius by HR-pQCT   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change from the parent study baseline in trabecular BMD at the distal radius by HR-pQCT
Measure Description Percent change from the 20050179 baseline in trabecular BMD at the distal radius as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 37
Percent change from the parent study baseline in trabecular BMD at the distal radius by HR-pQCT
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
5.1 (2.3 to 8.0) 5.9 (2.8 to 9.0)


Statistical Analysis 1 for Percent change from the parent study baseline in trabecular BMD at the distal radius by HR-pQCT
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.6560
Mean Difference (Final Values) [5] 0.7
95% Confidence Interval ( -2.5 to 4.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


5. Secondary:  Percent change from the parent study baseline in cortical thickness at the distal tibia by HR-pQCT   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change from the parent study baseline in cortical thickness at the distal tibia by HR-pQCT
Measure Description Percent change from the 20050179 baseline in cortical thickness at the distal tibia as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 40
Percent change from the parent study baseline in cortical thickness at the distal tibia by HR-pQCT
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
-6.4 (-7.8 to -5.1) -4.6 (-5.9 to -3.3)


Statistical Analysis 1 for Percent change from the parent study baseline in cortical thickness at the distal tibia by HR-pQCT
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0594
Mean Difference (Final Values) [5] 1.8
95% Confidence Interval ( -0.1 to 3.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


6. Secondary:  Percent change from the parent study baseline in total BMD at the distal tibia by HR-pQCT   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change from the parent study baseline in total BMD at the distal tibia by HR-pQCT
Measure Description Percent change from the 20050179 baseline in total BMD at the distal tibia as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 40
Percent change from the parent study baseline in total BMD at the distal tibia by HR-pQCT
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
-1.6 (-2.8 to -0.4) 1.0 (-0.2 to 2.2)


Statistical Analysis 1 for Percent change from the parent study baseline in total BMD at the distal tibia by HR-pQCT
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0032
Mean Difference (Final Values) [5] 2.6
95% Confidence Interval ( 0.9 to 4.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


7. Secondary:  Percent change from the parent study baseline in cortical BMD at the distal tibia by HR-pQCT   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change from the parent study baseline in cortical BMD at the distal tibia by HR-pQCT
Measure Description Percent change from the 20050179 baseline in cortical BMD at the distal tibia as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 40
Percent change from the parent study baseline in cortical BMD at the distal tibia by HR-pQCT
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
-1.0 (-1.7 to -0.3) -0.6 (-1.4 to 0.2)


Statistical Analysis 1 for Percent change from the parent study baseline in cortical BMD at the distal tibia by HR-pQCT
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.2897
Mean Difference (Final Values) [5] 0.4
95% Confidence Interval ( -0.4 to 1.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


8. Secondary:  Percent change from the parent study baseline in trabecular BMD at the distal tibia by HR-pQCT   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change from the parent study baseline in trabecular BMD at the distal tibia by HR-pQCT
Measure Description Percent change from the 20050179 baseline in trabecular BMD at the distal tibia as determined by HR-pQCT at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 40
Percent change from the parent study baseline in trabecular BMD at the distal tibia by HR-pQCT
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
2.9 (1.0 to 4.9) 6.8 (4.9 to 8.8)


Statistical Analysis 1 for Percent change from the parent study baseline in trabecular BMD at the distal tibia by HR-pQCT
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0067
Mean Difference (Final Values) [5] 3.9
95% Confidence Interval ( 1.1 to 6.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


9. Secondary:  Percent change of distal 1/3 radius BMD from the parent study baseline by DXA   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change of distal 1/3 radius BMD from the parent study baseline by DXA
Measure Description Percent change of distal 1/3 radius BMD from the 20050179 baseline as determined by DXA at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 40
Percent change of distal 1/3 radius BMD from the parent study baseline by DXA
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
-2.0 (-3.3 to -0.8) 0.0 (-1.2 to 1.2)


Statistical Analysis 1 for Percent change of distal 1/3 radius BMD from the parent study baseline by DXA
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0184
Mean Difference (Final Values) [5] 2.1
95% Confidence Interval ( 0.4 to 3.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


10. Secondary:  Percent change of ultradistal radius BMD from the parent study baseline by DXA   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change of ultradistal radius BMD from the parent study baseline by DXA
Measure Description Percent change of ultradistal radius BMD from the 20050179 baseline as determined by DXA at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 40
Percent change of ultradistal radius BMD from the parent study baseline by DXA
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
-3.5 (-4.9 to -2.2) -1.9 (-3.3 to -0.6)


Statistical Analysis 1 for Percent change of ultradistal radius BMD from the parent study baseline by DXA
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0911
Mean Difference (Final Values) [5] 1.6
95% Confidence Interval ( -0.3 to 3.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


11. Secondary:  Percent change of total radius BMD from the parent study baseline by DXA   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Percent change of total radius BMD from the parent study baseline by DXA
Measure Description Percent change of total radius BMD from the 20050179 baseline as determined by DXA at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179.
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 40
Percent change of total radius BMD from the parent study baseline by DXA
[units:Percent]
Least Squares Mean ( 95% Confidence Interval )
-3.0 (-4.0 to -2.0) -0.9 (-1.9 to 0.1)


Statistical Analysis 1 for Percent change of total radius BMD from the parent study baseline by DXA
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0035
Mean Difference (Final Values) [5] 2.1
95% Confidence Interval ( 0.7 to 3.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


12. Secondary:  Actual Value of Serum Type I C-telopeptide   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Actual Value of Serum Type I C-telopeptide
Measure Description Actual value at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 40
Actual Value of Serum Type I C-telopeptide
[units:ng/mL]
Least Squares Mean ( 95% Confidence Interval )
0.6 (0.5 to 0.6) 0.7 (0.6 to 0.7)


Statistical Analysis 1 for Actual Value of Serum Type I C-telopeptide
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0591
Other [5] 1.1
95% Confidence Interval ( 1.0 to 1.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.


13. Secondary:  Actual Value of Procollagen Type 1 N-terminal Peptide   [ Time Frame: Day 1 ]
Measure Type Secondary
Measure Name Actual Value of Procollagen Type 1 N-terminal Peptide
Measure Description Actual value at Month 32 (close to mean and median) since last subcutaneous dose of denosumab or placebo in study 20050179
Time Frame Day 1
Safety Issue? No

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects with observed data and baseline

Reporting Groups
  Description
Previous Placebo Treatment Group Subjects who had previously received placebo and completed Study 20050179. No study drug was administered during this study.
Previous Denosumab 60 mg Q6M Treatment Group Subjects who had previously received denosumab and completed Study 20050179. No study drug was administered during this study.

Measured Values
  Previous Placebo Treatment Group Previous Denosumab 60 mg Q6M Treatment Group
Number of Participants Analyzed
[units:participants]
39 40
Actual Value of Procollagen Type 1 N-terminal Peptide
[units:µg/L]
Least Squares Mean ( 95% Confidence Interval )
49.8 (45.6 to 54.3) 58.9 (54.1 to 64.2)


Statistical Analysis 1 for Actual Value of Procollagen Type 1 N-terminal Peptide
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] No
Method [3] ANCOVA
P-Value [4] 0.0079
Other [5] 1.2
95% Confidence Interval ( 1.0 to 1.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Additional details about a non-inferiority or equivalence analysis:
  No text entered.
[3] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.
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Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


Results Point of Contact: 
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436