Bone Histomorphometry in Postmenopausal Men and Women With Osteoarthritis Undergoing Total Hip Replacement

• ClinicalTrials.gov Identifier: NCT02576652
• Recruitment Status: Completed
• First Posted: October 15, 2015
• Results First Posted: April 26, 2019
• Last Update Posted: April 26, 2019
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

• Study Type: Interventional
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Osteoporosis
• Interventions: Other: Tetracycline; Other: Demeclocycline; Procedure: Total Hip Replacement
• Enrollment: 6

Participant Flow

Recruitment Details	This study was conducted at one center in the United States.
Pre-assignment Details

Arm/Group Title	Osteoarthritis Participants
Arm/Group Description	Participants previously treated with denosumab and planning to undergo total hip replacement (THR) received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after the last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline.
Period Title: Overall Study
Started	6
Completed	4
Not Completed	2
Reason Not Completed
Withdrawal by Subject	2

Baseline Characteristics

Arm/Group Title		Osteoarthritis Participants
Arm/Group Description		Participants previously treated with denosumab and planning to undergo total hip replacement (THR) received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after the last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline.
Overall Number of Baseline Participants		6
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	6 participants
		68.7 (8.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants
	Female	6 100.0%
	Male	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	6 100.0%
	Unknown or Not Reported	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants
	White	6 100.0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Modeling Based Bone Formation in the Femoral Neck
Description	Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Modeling based formation units in active bone‐forming, tetracycline‐labeled surfaces were identified by a smooth cement line. The percentage of participants with fluorochrome labeling present in the cancellous or periosteal, or endocortical surfaces of the femoral neck indicative of modeling-based bone formation is reported.
Time Frame	Days 22-58 (at the time of hip replacement surgery)

Outcome Measure Data

Analysis Population Description

All enrolled participants who had an evaluable biopsy for fluorochrome labeling.

Arm/Group Title	Osteoarthritis Participants
Arm/Group Description:	Participants previously treated with denosumab and planning to undergo total hip replacement (THR) received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after the last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline.
Overall Number of Participants Analyzed	4
Measure Type: Number; Unit of Measure: percentage of participants
	100

2. Secondary Outcome

Title	Modeling Based Formation Units in the Femoral Neck
Description	Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Modeling based formation units in active bone‐forming, tetracycline‐labeled surfaces were identified by a smooth cement line. The number of modeling based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface.
Time Frame	Days 22-58 (at the time of hip replacement surgery)

Outcome Measure Data

Analysis Population Description

Enrolled participants who had an evaluable biopsy for fluorochrome labeling.

Arm/Group Title	Osteoarthritis Participants
Arm/Group Description:	Participants previously treated with denosumab and planning to undergo total hip replacement (THR) received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after the last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline.
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: units/mm
Cancellous Region	0.1455 (0.2097)
Endocortical Region	0.2223 (0.2306)
Periosteal Region	0.1990 (0.1409)

3. Secondary Outcome

Title	Overfilled Remodeling-based Formation Units in the Femoral Neck
Description	Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Remodeling-based formation units in active bone‐forming, tetracycline‐labeled surfaces were identified by a scalloped cement line. The number of overfilled remodeling-based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported as units per mm of bone surface.
Time Frame	Days 22-58 (at the time of hip replacement surgery)

Outcome Measure Data

Analysis Population Description

Enrolled participants who had an evaluable biopsy for fluorochrome labeling.

Arm/Group Title	Osteoarthritis Participants
Arm/Group Description:	Participants previously treated with denosumab and planning to undergo total hip replacement (THR) received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after the last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline.
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: units/mm
Cancellous Region	0.0038 (0.0062)
Endocortical Region	0.0108 (0.0138)
Periosteal Region	0.0000 (0.0000)

4. Secondary Outcome

Title	Remodeling-based Formation Units Including Overfilled Units in the Femoral Neck
Description	Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Remodeling based formation units in active bone‐forming, tetracycline‐labeled surfaces were identified by a scalloped cement line. The number of remodeling based formation units including overfilled units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface.
Time Frame	Days 22-58 (at the time of hip replacement surgery)

Outcome Measure Data

Analysis Population Description

Enrolled participants who had an evaluable biopsy for fluorochrome labeling.

Arm/Group Title	Osteoarthritis Participants
Arm/Group Description:	Participants previously treated with denosumab and planning to undergo total hip replacement (THR) received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after the last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline.
Overall Number of Participants Analyzed	4
Mean (Standard Deviation); Unit of Measure: units/mm
Cancellous Region	0.0285 (0.0174)
Endocortical Region	0.0323 (0.0318)
Periosteal Region	0.0033 (0.0065)

Adverse Events

Time Frame	From the date of first administration of fluorochrome treatment (tetracycline or democlocycline or their derivatives) until the date of THP surgery (up to 58 days).
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Total Hip Replacement
Arm/Group Description	Participants previously treated with denosumab and planning to undergo THR received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after the receipt of the last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline.
All-Cause Mortality
	Total Hip Replacement
	Affected / at Risk (%)
Total	0/6 (0.00%)
Serious Adverse Events
	Total Hip Replacement
	Affected / at Risk (%)
Total	1/6 (16.67%)
Infections and infestations
Arthritis infective † 1	1/6 (16.67%)
1 Term from vocabulary, MedDRA 20.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Total Hip Replacement
	Affected / at Risk (%)
Total	2/6 (33.33%)
Immune system disorders
Hypersensitivity † 1	1/6 (16.67%)
Skin and subcutaneous tissue disorders
Urticaria † 1	1/6 (16.67%)
1 Term from vocabulary, MedDRA 20.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

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 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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Amgen Inc.
• Phone: 866-572-6436
• EMail: medinfo@amgen.com

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02576652 History of Changes
• Other Study ID Numbers: 20140259
• First Submitted: May 26, 2015
• First Posted: October 15, 2015
• Results First Submitted: December 6, 2018
• Results First Posted: April 26, 2019
• Last Update Posted: April 26, 2019