A Multicenter, Randomized Placebo Controlled Pilot MicroCT Study to Estimate the Effect of Treatment With Denosumab (AMG 162) and Alendronate Sodium in Postmenopausal Women With Low Bone Mineral Density

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00293813
• Collaborator: (none)
• Enrollment: 247
• Arms: 3
• Duration (Months): 27

Study Details

Study Description

Brief Summary

This study is structured to estimate the effect of denosumab, compared to placebo and alendronate, on several bone parameters.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: Alendronate; Drug: Denosumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 247 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized Placebo Controlled Pilot MicroCT Study to Estimate the Effect of Treatment With Denosumab (AMG 162) and Alendronate Sodium in Postmenopausal Women With Low Bone Mineral Density
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 3 Placebo for denosumab and placebo for alendronate	Drug: Placebo; Placebo for alendronate and placebo for denosumab
Experimental: 1 denosumab and placebo for alendronate	Drug: Denosumab; denosumab 60 mg SC q 6 mos
Active Comparator: 2 Placebo for denosumab and alendronate	Drug: Alendronate; Alendronate 70 mg PO QW

Outcome Measures

Primary Outcome Measures

1. Cortical Thickness of Radius by XtremeCT Percent Change From Baseline at Month 12 [12 months]

   Cortical Thickness measured by XtremeCT.

Secondary Outcome Measures

1. Cortical Thickness of Tibia by XtremeCT Percent Change From Baseline at Month 12 [12 months]

   Cortical Thickness measured by XtremeCT.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Postmenopausal, ambulatory women between 50 and 70 years old who are generally in good health.

• Must have low bone mineral density and meet specific eligibility criteria.

Key Exclusion Criteria:

-Subjects must not currently be receiving any medication that affects bone metabolism or have an underlying condition that affects their ability to take alendronate or receive denosumab.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, Kearns A, Thomas T, Boyd SK, Boutroy S, Bogado C, Majumdar S, Fan M, Libanati C, Zanchetta J. Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res. 2010 Aug;25(8):1886-94. doi: 10.1002/jbmr.81.
• Zebaze RM, Libanati C, Austin M, Ghasem-Zadeh A, Hanley DA, Zanchetta JR, Thomas T, Boutroy S, Bogado CE, Bilezikian JP, Seeman E. Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone. 2014 Feb;59:173-9. doi: 10.1016/j.bone.2013.11.016. Epub 2013 Nov 22.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00293813
• Other Study ID Numbers: 20050179
• First Posted: Feb 20, 2006
• Last Update Posted: Jul 25, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Amgen: Post Menopausal; Osteoporosis; MicroCT; Amgen; denosumab; Extreme CT; XCT; Fosamax; Alendronate
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Bone Diseases, Metabolic; Denosumab; Alendronate

Study Results

Participant Flow

Arm/Group Title	Alendronate 70 mg QW	Denosumab 60 mg Q6M	Placebo
Arm/Group Description	Alendronate 70 mg QW	Denosumab 60 mg Q6M	Placebo
Period Title: Overall Study
STARTED	82	83	82
COMPLETED	69	74	74
NOT COMPLETED	13	9	8

Baseline Characteristics

Arm/Group Title	Alendronate 70 mg QW	Denosumab 60 mg Q6M	Placebo	Total
Arm/Group Description	Alendronate 70 mg QW	Denosumab 60 mg Q6M	Placebo	Total of all reporting groups
Overall Participants	82	83	82	247
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.7 (5.2)	60.3 (5.9)	60.8 (5.2)	60.6 (5.4)
Sex: Female, Male (Count of Participants)
Female	82 100%	83 100%	82 100%	247 100%
Male	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Cortical Thickness of Radius by XtremeCT Percent Change From Baseline at Month 12
Description	Cortical Thickness measured by XtremeCT.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Randomized subjects who receive at least 1 dose of investigational product and have a baseline and at least 1 post baseline evaluation before or at month 12. Last Observation Carried Forward used as imputation method. Summarised for actual treatment taken.

Arm/Group Title	Alendronate 70 mg QW	Denosumab 60 mg Q6M	Placebo
Arm/Group Description	Alendronate 70 mg QW	Denosumab 60 mg Q6M	Placebo
Measure Participants	73	75	79
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	2.4	3.4	-.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg Q6M, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.1
	Confidence Interval	() 95%; 2.6 to 5.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alendronate 70 mg QW, Denosumab 60 mg Q6M
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1
	Confidence Interval	() 95%; -.6 to 2.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Cortical Thickness of Tibia by XtremeCT Percent Change From Baseline at Month 12
Description	Cortical Thickness measured by XtremeCT.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alendronate 70 mg QW	Denosumab 60 mg Q6M	Placebo
Arm/Group Description	Alendronate 70 mg QW	Denosumab 60 mg Q6M	Placebo
Measure Participants	73	78	79
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	4.9	5.8	1.4

Adverse Events

Arm/Group Title	Placebo		Alendronate 70 mg QW		Denosumab 60 mg Q6M
Arm/Group Description
All Cause Mortality
	Placebo		Alendronate 70 mg QW		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Alendronate 70 mg QW		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/83 (6%)		5/81 (6.2%)		2/83 (2.4%)
Hepatobiliary disorders
Biliary colic	0/83 (0%)		1/81 (1.2%)		0/83 (0%)
Cholecystitis acute	0/83 (0%)		0/81 (0%)		1/83 (1.2%)
Cholelithiasis	2/83 (2.4%)		0/81 (0%)		0/83 (0%)
Infections and infestations
Pneumonia	1/83 (1.2%)		0/81 (0%)		0/83 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/83 (0%)		0/81 (0%)		1/83 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of the cervix	0/83 (0%)		1/81 (1.2%)		0/83 (0%)
Breast cancer	0/83 (0%)		2/81 (2.5%)		0/83 (0%)
Nervous system disorders
Amnesia	1/83 (1.2%)		0/81 (0%)		0/83 (0%)
Loss of consciousness	0/83 (0%)		1/81 (1.2%)		1/83 (1.2%)
Psychiatric disorders
Confusional state	1/83 (1.2%)		0/81 (0%)		0/83 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Alendronate 70 mg QW		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/83 (94%)		77/81 (95.1%)		76/83 (91.6%)
Gastrointestinal disorders
Abdominal pain	3/83 (3.6%)		9/81 (11.1%)		2/83 (2.4%)
Abdominal pain upper	8/83 (9.6%)		10/81 (12.3%)		5/83 (6%)
Constipation	12/83 (14.5%)		13/81 (16%)		15/83 (18.1%)
Diarrhoea	9/83 (10.8%)		10/81 (12.3%)		3/83 (3.6%)
Dyspepsia	7/83 (8.4%)		9/81 (11.1%)		5/83 (6%)
Nausea	6/83 (7.2%)		5/81 (6.2%)		6/83 (7.2%)
Vomiting	5/83 (6%)		6/81 (7.4%)		3/83 (3.6%)
Infections and infestations
Bronchitis	11/83 (13.3%)		11/81 (13.6%)		9/83 (10.8%)
Influenza	15/83 (18.1%)		10/81 (12.3%)		14/83 (16.9%)
Nasopharyngitis	14/83 (16.9%)		8/81 (9.9%)		10/83 (12%)
Pharyngitis	1/83 (1.2%)		7/81 (8.6%)		6/83 (7.2%)
Urinary tract infection	5/83 (6%)		0/81 (0%)		4/83 (4.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/83 (9.6%)		8/81 (9.9%)		10/83 (12%)
Back pain	10/83 (12%)		6/81 (7.4%)		10/83 (12%)
Muscle spasms	5/83 (6%)		2/81 (2.5%)		5/83 (6%)
Musculoskeletal pain	1/83 (1.2%)		7/81 (8.6%)		4/83 (4.8%)
Osteoarthritis	5/83 (6%)		2/81 (2.5%)		3/83 (3.6%)
Pain in extremity	10/83 (12%)		10/81 (12.3%)		10/83 (12%)
Nervous system disorders
Dizziness	4/83 (4.8%)		4/81 (4.9%)		6/83 (7.2%)
Headache	9/83 (10.8%)		12/81 (14.8%)		6/83 (7.2%)
Paraesthesia	2/83 (2.4%)		4/81 (4.9%)		5/83 (6%)
Reproductive system and breast disorders
Breast mass	3/83 (3.6%)		2/81 (2.5%)		5/83 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	5/83 (6%)		4/81 (4.9%)		2/83 (2.4%)
Skin and subcutaneous tissue disorders
Rash	1/83 (1.2%)		2/81 (2.5%)		6/83 (7.2%)
Vascular disorders
Hypertension	6/83 (7.2%)		5/81 (6.2%)		5/83 (6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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 multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.