Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01753856
First received: December 18, 2012
Last updated: September 11, 2015
Last verified: September 2015
Results First Received: June 9, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Osteoporosis
Interventions: Drug: Teriparatide
Drug: Denosumab
Drug: Demeclocycline
Drug: Tetracycline
Drug: Calcium Supplement
Drug: Vitamin D

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Tetracycline (TET) and demeclocycline (DEM) temporarily bind to new bone and are detected as different colors under ultraviolet light in bone biopsy samples. In this study, participants were administered DEM prior to randomization (baseline) and again with TET 22 days prior to bone biopsy obtained 3 months post first dose of study drug.

Reporting Groups
  Description
Teriparatide

Teriparatide: 20-microgram (µg) subcutaneous (SC) injection once daily for 6 months.

DEM: 150-milligram (mg) tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 milligrams per day (mg/day) administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 International Units per day (IU/day) administered orally for 6 months.

Denosumab

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.


Participant Flow:   Overall Study
    Teriparatide     Denosumab  
STARTED     33     36  
Received at Least 1 Dose of Study Drug     33     36  
Completed 3-Month Bone Biopsy     31     35  
COMPLETED     30     34  
NOT COMPLETED     3     2  
Adverse Event                 1                 0  
Withdrawal by Subject                 0                 2  
Sponsor Decision                 2                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

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.
Randomized participants who received at least 1 dose of study drug (teriparatide or denosumab).

Reporting Groups
  Description
Teriparatide

Teriparatide: 20-µg SC injection once daily for 6 months.

DEM: 150-mg tablets administered orally, on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Denosumab

Denosumab: A single 60-mg SC injection.

DEM: 150-mg tablets administered orally on the following days, 18 days prior to randomization:

  • Days 1, 2, 3, 16, 17, and 18: 150 mg DEM every 6 hours.
  • Days 4 through 15: DEM was not administered.

TET: 250-mg capsules administered orally on the following days, 22 days prior to biopsy procedure:

  • Days 1, 2, 3, 16, 17, and 18: 250 mg TET every 6 hours.
  • Days 4 through 15: TET was not administered.

Calcium Supplements: Approximately 1000 mg/day administered orally for 6 months.

Vitamin D Supplements: Approximately 800 to 1200 IU/day administered orally for 6 months.

Total Total of all reporting groups

Baseline Measures
    Teriparatide     Denosumab     Total  
Number of Participants  
[units: participants]
  33     36     69  
Age  
[units: years]
Mean (Standard Deviation)
  61.58  (5.84)     65.17  (8.32)     63.45  (7.42)  
Gender  
[units: participants]
     
Female     33     36     69  
Male     0     0     0  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     2     3     5  
Not Hispanic or Latino     31     32     63  
Unknown or Not Reported     0     1     1  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     0     2     2  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     1     2     3  
White     31     31     62  
More than one race     1     1     2  
Unknown or Not Reported     0     0     0  
Region of Enrollment  
[units: participants]
     
United States     21     27     48  
Canada     12     9     21  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies   [ Time Frame: Baseline, 3 months post first dose of study drug ]

2.  Secondary:   Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies   [ Time Frame: 3 months post first dose of study drug ]

3.  Secondary:   Change From Baseline to 3 Months in MS/BS in the Endocortical Compartment (EC), Intracortical Compartment (IC), and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies   [ Time Frame: Baseline, 3 months post first dose of study drug ]

4.  Secondary:   MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug   [ Time Frame: 3 months post first dose of study drug ]

5.  Secondary:   Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies   [ Time Frame: 3 months post first dose of study drug ]

6.  Secondary:   Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies   [ Time Frame: 3 months post first dose of study drug ]

7.  Secondary:   Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies   [ Time Frame: 3 months post first dose of study drug ]

8.  Secondary:   Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies   [ Time Frame: Baseline, 3 months post first dose of study drug ]

9.  Secondary:   Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies   [ Time Frame: Baseline, 3 months post first dose of study drug ]

10.  Secondary:   Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies   [ Time Frame: Baseline, 3 months post first dose of study drug ]

11.  Secondary:   Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies   [ Time Frame: 3 months post first dose of study drug ]

12.  Secondary:   Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH)   [ Time Frame: Baseline, 1, 3, and 6 months post first dose of study drug ]

13.  Secondary:   Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP)   [ Time Frame: Baseline, 1, 3, and 6 months post first dose of study drug ]

14.  Secondary:   Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin   [ Time Frame: Baseline, 1, 3, and 6 months post first dose of study drug ]

15.  Secondary:   Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX)   [ Time Frame: Baseline, 1, 3, and 6 months post first dose of study drug ]

16.  Secondary:   Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest   [ Time Frame: 3 months post first dose of study drug ]

17.  Secondary:   Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest   [ Time Frame: 3 months post first dose of study drug ]

18.  Secondary:   Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the CC of the Iliac Crest   [ Time Frame: 3 months post first dose of study drug ]

19.  Secondary:   Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest   [ Time Frame: 3 months post first dose of study drug ]

20.  Secondary:   Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest   [ Time Frame: 3 months post first dose of study drug ]

21.  Secondary:   Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest   [ Time Frame: 3 months post first dose of study drug ]

22.  Secondary:   Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest   [ Time Frame: 3 months post first dose of study drug ]

23.  Other Pre-specified:   Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest   [ Time Frame: 3 months post first dose of study drug ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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.


  More Information
  Hide More Information

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 Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979



Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01753856     History of Changes
Other Study ID Numbers: 14592
B3D-US-GHDV ( Other Identifier: Eli Lilly and Company )
Study First Received: December 18, 2012
Results First Received: June 9, 2015
Last Updated: September 11, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada