Study to Evaluate AMG 162 in the Prevention of Postmenopausal Osteoporosis

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00091793
• Collaborator: (none)
• Enrollment: 332
• Arms: 2
• Duration (Months): 55

Study Details

Study Description

Brief Summary

This study will determine whether treatment with AMG 162 can prevent lumbar spine bone loss in both early and late postmenopausal women with osteopenia, and to further test the safety and tolerability of AMG 162 in this population.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: AMG 162; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 332 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-Blind Study to Evaluate AMG 162 in the Prevention of Postmenopausal Osteoporosis
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMG 162 60 mg/mL denosumab given day 1, month 6, month 12 and month 18	Drug: AMG 162; 60 mg/mL denosumab given day 1, month 6, month 12 and month 18
Placebo Comparator: Placebo Placebo given day 1, month 6, month 12 and month 18	Drug: Placebo; Placebo given at day 1, month 6, month 12 and month 18

Outcome Measures

Primary Outcome Measures

1. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24 [24 Months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

Secondary Outcome Measures

1. Total Hip Bone Mineral Density Percent Change From Baseline at Month 24 [24 Months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

2. Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 24 [24 Months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

3. Trochanter Bone Mineral Density Percent Change From Baseline at Month 24 [24 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

4. Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24 [24 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

5. Total Body (Without Head) Bone Mineral Density Percent Change From Baseline at Month 24 [24 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.

6. Distal Radius Trabecular Volumetric Bone Mineral Density Percent Change From Baseline at Month 24 [24 months]

   Volumetric Bone Mineral Density Assessed by Quantitative Computerized Tomography (QCT).

7. Distal Radius Cortical Volumetric Bone Mineral Density Percent Change From Baseline at Month 24 [24 months]

   Volumetric Bone Mineral Density Assessed by Quantitative Computerized Tomography (QCT).

8. Distal Radius Total Volumetric Bone Mineral Density Percent Change From Baseline at Month 24 [24 months]

   Volumetric Bone Mineral Density Assessed by Quantitative Computerized Tomography (QCT).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 90 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Eligibility Criteria

• Postmenopausal women with Osteopenia (lumbar spine bone mineral density T-score between 1.0 and -2.5)

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
• Notice regarding posted summaries of trial results

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00091793
• Other Study ID Numbers: 20040132
• First Posted: Sep 21, 2004
• Last Update Posted: Dec 31, 2010
• Last Verified: Dec 1, 2010

• Keywords provided by , ,: Osteoporosis; Postmenopausal
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Denosumab

Study Results

Participant Flow

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	166	166
COMPLETED	142	144
NOT COMPLETED	24	22

Baseline Characteristics

Arm/Group Title	Denosumab 60 mg Q6M	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	166	166	332
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.8 (7.4)	58.9 (7.5)	59.4 (7.5)
Sex: Female, Male (Count of Participants)
Female	166 100%	166 100%	332 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

Randomized subjects who have a non-missing baseline and at least 1 non-missing postbaseline evaluation at or prior to month 24. LOCF was used as imputation method.

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	163	163
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	6.5	-.6

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	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7
	Confidence Interval	() 95%; 6.2 to 7.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	163	163
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	3.4	-1.1

3. Secondary Outcome

Title	Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 24
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	163	163
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	2.8	-.9

4. Secondary Outcome

Title	Trochanter Bone Mineral Density Percent Change From Baseline at Month 24
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	163	163
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	5.2	-.8

5. Secondary Outcome

Title	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	156	156
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	1.4	-2.1

6. Secondary Outcome

Title	Total Body (Without Head) Bone Mineral Density Percent Change From Baseline at Month 24
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	156	154
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	2.4	-1.4

7. Secondary Outcome

Title	Distal Radius Trabecular Volumetric Bone Mineral Density Percent Change From Baseline at Month 24
Description	Volumetric Bone Mineral Density Assessed by Quantitative Computerized Tomography (QCT).
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	144	131
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	8.7	-.7

8. Secondary Outcome

Title	Distal Radius Cortical Volumetric Bone Mineral Density Percent Change From Baseline at Month 24
Description	Volumetric Bone Mineral Density Assessed by Quantitative Computerized Tomography (QCT).
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	156	152
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	.3	-1.4

9. Secondary Outcome

Title	Distal Radius Total Volumetric Bone Mineral Density Percent Change From Baseline at Month 24
Description	Volumetric Bone Mineral Density Assessed by Quantitative Computerized Tomography (QCT).
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Denosumab 60 mg Q6M	Placebo
Arm/Group Description
Measure Participants	156	153
Least Squares Mean (95% Confidence Interval) [Percent Change from Baseline]	.8	-1.9

Adverse Events

Arm/Group Title	Placebo		Denosumab 60 mg Q6M
Arm/Group Description
All Cause Mortality
	Placebo		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/165 (5.5%)		18/164 (11%)
Gastrointestinal disorders
Colitis ischaemic	0/165 (0%)		1/164 (0.6%)
Colonic polyp	0/165 (0%)		1/164 (0.6%)
Hepatobiliary disorders
Cholelithiasis	1/165 (0.6%)		0/164 (0%)
Infections and infestations
Appendicitis	0/165 (0%)		1/164 (0.6%)
Cellulitis	0/165 (0%)		1/164 (0.6%)
Diverticulitis	0/165 (0%)		2/164 (1.2%)
Lobar pneumonia	1/165 (0.6%)		0/164 (0%)
Pneumonia	0/165 (0%)		3/164 (1.8%)
Pyelonephritis	0/165 (0%)		1/164 (0.6%)
Sepsis	0/165 (0%)		2/164 (1.2%)
Urinary tract infection	0/165 (0%)		1/164 (0.6%)
Injury, poisoning and procedural complications
Incisional hernia, obstructive	0/165 (0%)		1/164 (0.6%)
Patella fracture	0/165 (0%)		1/164 (0.6%)
Tibia fracture	1/165 (0.6%)		0/164 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/165 (0.6%)		0/164 (0%)
Intervertebral disc protrusion	1/165 (0.6%)		1/164 (0.6%)
Osteoarthritis	0/165 (0%)		2/164 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	1/165 (0.6%)		0/164 (0%)
Breast cancer in situ	0/165 (0%)		1/164 (0.6%)
Mycosis fungoides	0/165 (0%)		1/164 (0.6%)
Ovarian cancer	0/165 (0%)		1/164 (0.6%)
Uterine cancer	0/165 (0%)		1/164 (0.6%)
Nervous system disorders
Facial palsy	1/165 (0.6%)		0/164 (0%)
Psychiatric disorders
Depression	1/165 (0.6%)		0/164 (0%)
Reproductive system and breast disorders
Pelvic prolapse	0/165 (0%)		1/164 (0.6%)
Uterine perforation	1/165 (0.6%)		0/164 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	157/165 (95.2%)		156/164 (95.1%)
Gastrointestinal disorders
Abdominal pain	7/165 (4.2%)		9/164 (5.5%)
Constipation	8/165 (4.8%)		18/164 (11%)
Diarrhoea	7/165 (4.2%)		14/164 (8.5%)
Dyspepsia	10/165 (6.1%)		9/164 (5.5%)
Gastrooesophageal reflux disease	6/165 (3.6%)		9/164 (5.5%)
Nausea	12/165 (7.3%)		16/164 (9.8%)
General disorders
Fatigue	12/165 (7.3%)		7/164 (4.3%)
Infections and infestations
Influenza	18/165 (10.9%)		15/164 (9.1%)
Nasopharyngitis	31/165 (18.8%)		36/164 (22%)
Sinusitis	17/165 (10.3%)		10/164 (6.1%)
Upper respiratory tract infection	22/165 (13.3%)		19/164 (11.6%)
Urinary tract infection	17/165 (10.3%)		18/164 (11%)
Injury, poisoning and procedural complications
Procedural pain	5/165 (3%)		9/164 (5.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	42/165 (25.5%)		41/164 (25%)
Back pain	33/165 (20%)		33/164 (20.1%)
Muscle spasms	13/165 (7.9%)		12/164 (7.3%)
Myalgia	12/165 (7.3%)		11/164 (6.7%)
Pain in extremity	20/165 (12.1%)		24/164 (14.6%)
Shoulder pain	10/165 (6.1%)		17/164 (10.4%)
Nervous system disorders
Dizziness	9/165 (5.5%)		7/164 (4.3%)
Headache	19/165 (11.5%)		26/164 (15.9%)
Hypoaesthesia	9/165 (5.5%)		5/164 (3%)
Psychiatric disorders
Depression	6/165 (3.6%)		10/164 (6.1%)
Insomnia	15/165 (9.1%)		13/164 (7.9%)
Respiratory, thoracic and mediastinal disorders
Cough	5/165 (3%)		11/164 (6.7%)
Pharyngolaryngeal pain	5/165 (3%)		15/164 (9.1%)
Skin and subcutaneous tissue disorders
Rash	5/165 (3%)		14/164 (8.5%)
Vascular disorders
Hypertension	14/165 (8.5%)		6/164 (3.7%)

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.