The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01221727
First received: October 14, 2010
Last updated: July 18, 2014
Last verified: July 2014
Results First Received: February 13, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Postmenopausal Osteoporosis
Interventions: Drug: Denosumab
Drug: Midazolam

  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
No text entered.

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
Midazolam With Denosumab 2 mg oral dose of Midazolam on Day 1 and Day 16, 60 mg subcutaneous dose of Denosumab on Day 2
Midazolam Only 2 mg oral dose of Midazolam on Day 1 and Day 16.

Participant Flow:   Overall Study
    Midazolam With Denosumab     Midazolam Only  
STARTED     21 [1]   9 [1]
Treated     19 [2]   8 [2]
COMPLETED     18     8  
NOT COMPLETED     3     1  
Physician Decision                 2                 0  
Withdrawal by Subject                 1                 1  
[1] Number of subjects randomized into the study
[2] Number of subjects received investigational product



  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
Midazolam With Denosumab 2 mg oral dose of Midazolam on Day 1 and Day 16, 60 mg subcutaneous dose of Denosumab on Day 2. Out of 21 subjects enrolled and randomized, 19 subjects received investigation product.
Midazolam Only 2 mg oral dose of Midazolam on Day 1 and Day 16. Out of 9 subjects enrolled and randomized, 8 subjects received investigation product.
Total Total of all reporting groups

Baseline Measures
    Midazolam With Denosumab     Midazolam Only     Total  
Number of Participants  
[units: participants]
  19     8     27  
Age  
[units: years]
Mean ± Standard Deviation
  64.42  ± 6.16     66.25  ± 5.34     64.96  ± 5.89  
Age, Customized  
[units: Participants]
     
<65 years     7     3     10  
>=65 years and <75 years     12     4     16  
>=75 years     0     1     1  
Gender  
[units: Participants]
     
Female     19     8     27  
Male     0     0     0  
Ethnicity (NIH/OMB)  
[units: Participants]
     
Hispanic or Latino     7     4     11  
Not Hispanic or Latino     12     4     16  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB)  
[units: Participants]
     
American Indian or Alaska Native     0     0     0  
Asian     1     1     2  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     1     1     2  
White     17     6     23  
More than one race     0     0     0  
Unknown or Not Reported     0     0     0  



  Outcome Measures
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1.  Primary:   Ratio of Pharmcokinetic (PK) Area Under the Concentration Time Curve (AUC) Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)   [ Time Frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose ]

2.  Primary:   Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group   [ Time Frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose ]

3.  Primary:   Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group   [ Time Frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose ]

4.  Primary:   Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)   [ Time Frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose ]

5.  Secondary:   Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)   [ Time Frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose ]

6.  Secondary:   Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group   [ Time Frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose ]

7.  Secondary:   Estimates of Inter- and Intra-subject Variability for PK Cmax Parameter for Midazolam Only Group   [ Time Frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose ]

8.  Secondary:   Summary of Serum Denosumab Concentration   [ Time Frame: Baseline (day 2 pre-dose) to day 16 ]

9.  Secondary:   Summary of Serum C-Telopeptide Concentration   [ Time Frame: Baseline (day 2 pre-dose) to day 16 ]

10.  Secondary:   Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration   [ Time Frame: Baseline (day 2 pre-dose) to day 16 ]

11.  Secondary:   Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)   [ Time Frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  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.


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


No publications provided


Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01221727     History of Changes
Other Study ID Numbers: 20101131
Study First Received: October 14, 2010
Results First Received: February 13, 2013
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration