Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00043186
First received: August 6, 2002
Last updated: September 6, 2013
Last verified: September 2013
Results First Received: December 22, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Low Bone Mineral Density
Interventions: Drug: Placebo
Drug: Denosumab
Drug: Alendronate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First Subject Enrolled: 11-May-2002 Last Subject Enrolled: 30-Apr-2003

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
Placebo Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42.
Denosumab 6 mg Q3M Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 14 mg Q3M Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 30 mg Q3M Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42.
Denosumab 14 mg Q6M Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 60 mg Q6M Participants received denosumab 60 mg SC every 6 months until Month 42.
Denosumab 100 mg Q6M Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 210 mg Q6M Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.
Alendronate 70 mg Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.

Participant Flow:   Overall Study
    Placebo     Denosumab 6 mg Q3M     Denosumab 14 mg Q3M     Denosumab 30 mg Q3M     Denosumab 14 mg Q6M     Denosumab 60 mg Q6M     Denosumab 100 mg Q6M     Denosumab 210 mg Q6M     Alendronate 70 mg  
STARTED     46     44     44     41     54     47     42     47     47  
COMPLETED     29     29     24     19     36     39     25     31     30  
NOT COMPLETED     17     15     20     22     18     8     17     16     17  
Physician Decision                 0                 0                 3                 0                 1                 0                 0                 1                 1  
Adverse Event                 2                 2                 2                 3                 2                 1                 2                 1                 3  
Withdrawal by Subject                 11                 8                 11                 13                 14                 6                 12                 9                 10  
Death                 0                 0                 1                 0                 0                 0                 2                 0                 0  
Disease progression                 1                 0                 0                 3                 0                 0                 0                 4                 0  
Ineligibility determined                 0                 0                 0                 0                 0                 0                 0                 0                 1  
Lost to Follow-up                 3                 5                 1                 1                 1                 1                 1                 1                 2  
Noncompliance                 0                 0                 1                 1                 0                 0                 0                 0                 0  
Other                 0                 0                 1                 1                 0                 0                 0                 0                 0  



  Baseline Characteristics
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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.
No text entered.

Reporting Groups
  Description
Placebo Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42.
Denosumab 6 mg Q3M Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 14 mg Q3M Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 30 mg Q3M Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42.
Denosumab 14 mg Q6M Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 60 mg Q6M Participants received denosumab 60 mg SC every 6 months until Month 42.
Denosumab 100 mg Q6M Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 210 mg Q6M Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.
Alendronate 70 mg Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
Total Total of all reporting groups

Baseline Measures
    Placebo     Denosumab 6 mg Q3M     Denosumab 14 mg Q3M     Denosumab 30 mg Q3M     Denosumab 14 mg Q6M     Denosumab 60 mg Q6M     Denosumab 100 mg Q6M     Denosumab 210 mg Q6M     Alendronate 70 mg     Total  
Number of Participants  
[units: participants]
  46     44     44     41     54     47     42     47     47     412  
Age  
[units: Years]
Mean ± Standard Deviation
  63.7  ± 9.1     62.8  ± 8.6     62.3  ± 6     61.2  ± 8.5     61.4  ± 8.1     63.1  ± 8.1     64.9  ± 8.2     60.5  ± 7.8     62.8  ± 8.2     62.5  ± 8.1  
Gender  
[units: Participants]
                   
Female     46     44     44     41     54     47     42     47     47     412  
Male     0     0     0     0     0     0     0     0     0     0  
Race/Ethnicity, Customized  
[units: Participants]
                   
White or Caucasian     37     33     42     36     49     39     37     42     40     355  
Black or African American     0     1     1     2     1     1     3     0     3     12  
Hispanic or Latino     8     8     1     3     3     5     2     5     4     39  
Asian     1     1     0     0     0     2     0     0     0     4  
Japanese     0     0     0     0     1     0     0     0     0     1  
American Indian or Alaska Native     0     1     0     0     0     0     0     0     0     1  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms   [ Time Frame: Baseline and Month 12 ]

2.  Secondary:   Serum CTX Percent Change From Baseline at Month 12   [ Time Frame: Baseline and Month 12 ]

3.  Secondary:   Urine NTX/Creatinine Percent Change From Baseline at Month 12   [ Time Frame: Baseline and Month 12 ]

4.  Secondary:   Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm   [ Time Frame: Baseline and Month 12 ]

5.  Secondary:   Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24   [ Time Frame: Baseline and 24 months ]

6.  Secondary:   Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36   [ Time Frame: Baseline and 36 months ]

7.  Secondary:   Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42   [ Time Frame: Baseline and 42 months ]

8.  Secondary:   Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48   [ Time Frame: Baseline and 48 months ]

9.  Secondary:   Serum CTX Percent Change From Baseline at Month 24   [ Time Frame: Baseline and 24 months ]

10.  Secondary:   Serum CTX Percent Change From Baseline at Month 36   [ Time Frame: Baseline and 36 months ]

11.  Secondary:   Serum CTX Percent Change From Baseline at Month 42   [ Time Frame: Baseline and 42 months ]

12.  Secondary:   Serum CTX Percent Change From Baseline at Month 48   [ Time Frame: Baseline and 48 months ]

13.  Secondary:   Urine NTX/Creatinine Percent Change From Baseline at Month 24   [ Time Frame: Baseline and 24 months ]

14.  Secondary:   Urine NTX/Creatinine Percent Change From Baseline at Month 36   [ Time Frame: Baseline and 36 months ]

15.  Secondary:   Urine NTX/Creatinine Percent Change From Baseline at Month 42   [ Time Frame: Baseline and 42 months ]

16.  Secondary:   Urine NTX/Creatinine Percent Change From Baseline at Month 48   [ Time Frame: Baseline and 48 months ]

17.  Secondary:   Total Hip Bone Mineral Density Percent Change From Baseline at Month 12   [ Time Frame: Baseline and 12 months ]

18.  Secondary:   Total Hip Bone Mineral Density Percent Change From Baseline at Month 24   [ Time Frame: Baseline and 24 months ]

19.  Secondary:   Total Hip Bone Mineral Density Percent Change From Baseline at Month 36   [ Time Frame: Baseline and 36 months ]

20.  Secondary:   Total Hip Bone Mineral Density Percent Change From Baseline at Month 42   [ Time Frame: Baseline and 42 months ]

21.  Secondary:   Total Hip Bone Mineral Density Percent Change From Baseline at Month 48   [ Time Frame: Baseline and 48 months ]

22.  Secondary:   Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12   [ Time Frame: Baseline and 12 months ]

23.  Secondary:   Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24   [ Time Frame: Baseline and 24 months ]

24.  Secondary:   Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36   [ Time Frame: Baseline and 36 months ]

25.  Secondary:   Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42   [ Time Frame: Baseline and 42 months ]

26.  Secondary:   Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48   [ Time Frame: Baseline and 48 months ]

27.  Secondary:   Total Body Bone Mineral Density Percent Change From Baseline at Month 12   [ Time Frame: Baseline and 12 months ]

28.  Secondary:   Total Body Bone Mineral Density Percent Change From Baseline at Month 24   [ Time Frame: Baseline and 24 months ]

29.  Secondary:   Total Body Bone Mineral Density Percent Change From Baseline at Month 36   [ Time Frame: Baseline and 36 months ]

30.  Secondary:   Total Body Bone Mineral Density Percent Change From Baseline at Month 42   [ Time Frame: Baseline and 42 months ]

31.  Secondary:   Total Body Bone Mineral Density Percent Change From Baseline at Month 48   [ Time Frame: Baseline and 48 months ]

32.  Secondary:   Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12   [ Time Frame: Baseline and 12 months ]

33.  Secondary:   Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24   [ Time Frame: Baseline and 24 months ]

34.  Secondary:   Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36   [ Time Frame: Baseline and 36 months ]

35.  Secondary:   Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42   [ Time Frame: Baseline and 42 months ]

36.  Secondary:   Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48   [ Time Frame: Baseline and 48 months ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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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


Publications of Results:

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00043186     History of Changes
Other Study ID Numbers: 20010223
Study First Received: August 6, 2002
Results First Received: December 22, 2009
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration