A Randomized, Double-blind, Placebo-controlled, Dose Response Study of AMG 162 (Denosumab) in Japanese Postmenopausal Osteoporotic Subjects

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00306189
• Collaborator: (none)
• Enrollment: 212
• Arms: 4
• Duration (Months): 22

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the effect of AMG 162 (denosumab) treatment on the lumbar spine BMD at month 12 and safety profile across the dose range tested (14, 60 and 100 mg SC once every 6 months) in Japanese postmenopausal osteoporotic subjects compared with those treated with placebo over 12 months.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: 100 mg AMG 162; Drug: 60 mg AMG 162; Drug: 14 mg AMG 162; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 212 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Dose Response Study of AMG 162 (Denosumab) in Subjects With Osteoporosis - A Randomized, Double-blind, Placebo-controlled, Dose Response Study of AMG 162 (Denosumab) in Japanese Postmenopausal Osteoporotic Subjects -
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jun 1, 2007
• Actual Study Completion Date: Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 100 mg AMG 162	Drug: 100 mg AMG 162; 100 mg AMG 162 (denosumab) SC every 6 months
Active Comparator: 60 mg AMG 162	Drug: 60 mg AMG 162; 60 mg AMG 162 (denosumab) SC every 6 months
Placebo Comparator: Placebo	Drug: Placebo; Placebo SC every 6 months
Active Comparator: 14 mg AMG 162	Drug: 14 mg AMG 162; 14 mg AMG 162 (denosumab) SC every 6 months

Outcome Measures

Primary Outcome Measures

1. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 [12 months]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria: - Ambulatory postmenopausal women. - BMD values (g/cm2, Hologic) must be lower than 0.714 at lumbar spine, 0.515 at femoral neck, 0.588 at total hip. - BMD values must not be lower than 0.535 at the lumbar spine, 0.406 at the femoral neck and 0.478 at the total hip. Exclusion Criteria: - Oral bisphosphonate treatments, PTH or PTH derivatives use within the last 12 months and administration of any of anti-osteoporotic treatments within the last 3 months before initial administration of the investigational product. - History of hypocalcemia. - More than two moderate vertebral fractures or any severe vertebral fracture.

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
• To access clinical trial results information click on this link

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00306189
• Other Study ID Numbers: 20050172; NOT APPRICABLE
• First Posted: Mar 23, 2006
• Last Update Posted: Jun 20, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Amgen: RANKL; RANK; denosumab; AMG 162; osteoporosis; bone turnover; bone mineral density; Japanese
• Additional relevant MeSH terms: Osteoporosis; Denosumab

Study Results

Participant Flow

Arm/Group Title	Denosumab 14 mg Q6M	Denosumab 60 mg Q6M	Denosumab 100 mg Q6M	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	57	56	56	57
COMPLETED	48	50	45	52
NOT COMPLETED	9	6	11	5

Baseline Characteristics

Arm/Group Title	Denosumab 14 mg Q6M	Denosumab 60 mg Q6M	Denosumab 100 mg Q6M	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	53	54	50	55	212
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.9 (7.1)	65.1 (6.3)	64.6 (7.1)	64.6 (7)	65.1 (6.8)
Sex: Female, Male (Count of Participants)
Female	53 100%	54 100%	50 100%	55 100%	212 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All subjects who received >= 1 dose of investigational product and have a baseline and >= 1 post baseline measurement at the lumbar spine.

Arm/Group Title	Placebo	Denosumab 14 mg Q6M	Denosumab 60 mg Q6M	Denosumab 100 mg Q6M
Arm/Group Description
Measure Participants	55	53	54	50
Mean (95% Confidence Interval) [Percent Change from Baseline]	.46	5.71	6.73	7.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Denosumab 100 mg Q6M
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7
	Confidence Interval	() 95%; 5.76 to 8.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Denosumab 14 mg Q6M
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.25
	Confidence Interval	() 95%; 4.1 to 6.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Denosumab 60 mg Q6M
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.27
	Confidence Interval	() 95%; 5.06 to 7.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Placebo		Denosumab 14 mg Q6M		Denosumab 60 mg Q6M		Denosumab 100 mg Q6M
Arm/Group Description
All Cause Mortality
	Placebo		Denosumab 14 mg Q6M		Denosumab 60 mg Q6M		Denosumab 100 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Denosumab 14 mg Q6M		Denosumab 60 mg Q6M		Denosumab 100 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/54 (7.4%)		6/53 (11.3%)		4/54 (7.4%)		2/51 (3.9%)
Cardiac disorders
Palpitations	0/54 (0%)		0/53 (0%)		1/54 (1.9%)		0/51 (0%)
Ear and labyrinth disorders
Meniere's disease	0/54 (0%)		1/53 (1.9%)		0/54 (0%)		0/51 (0%)
Gastrointestinal disorders
Colitis	1/54 (1.9%)		0/53 (0%)		0/54 (0%)		0/51 (0%)
Colitis ischaemic	0/54 (0%)		1/53 (1.9%)		0/54 (0%)		0/51 (0%)
Colonic polyp	0/54 (0%)		1/53 (1.9%)		0/54 (0%)		0/51 (0%)
Haemorrhoids	0/54 (0%)		0/53 (0%)		0/54 (0%)		1/51 (2%)
Intestinal ischaemia	0/54 (0%)		1/53 (1.9%)		0/54 (0%)		0/51 (0%)
Infections and infestations
Hepatitis C	1/54 (1.9%)		0/53 (0%)		0/54 (0%)		0/51 (0%)
Injury, poisoning and procedural complications
Subdural haematoma	0/54 (0%)		1/53 (1.9%)		0/54 (0%)		0/51 (0%)
Musculoskeletal and connective tissue disorders
Haemarthrosis	1/54 (1.9%)		0/53 (0%)		0/54 (0%)		0/51 (0%)
Intervertebral disc protrusion	1/54 (1.9%)		0/53 (0%)		0/54 (0%)		0/51 (0%)
Rotator cuff syndrome	0/54 (0%)		0/53 (0%)		1/54 (1.9%)		0/51 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/54 (0%)		0/53 (0%)		1/54 (1.9%)		0/51 (0%)
Nervous system disorders
Cerebral artery embolism	0/54 (0%)		0/53 (0%)		0/54 (0%)		1/51 (2%)
Cerebral infarction	0/54 (0%)		0/53 (0%)		1/54 (1.9%)		0/51 (0%)
Vascular disorders
Hypotension	0/54 (0%)		0/53 (0%)		1/54 (1.9%)		0/51 (0%)
Varicose vein	0/54 (0%)		1/53 (1.9%)		0/54 (0%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Denosumab 14 mg Q6M		Denosumab 60 mg Q6M		Denosumab 100 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/54 (90.7%)		50/53 (94.3%)		47/54 (87%)		48/51 (94.1%)
Cardiac disorders
Palpitations	0/54 (0%)		0/53 (0%)		3/54 (5.6%)		1/51 (2%)
Eye disorders
Cataract	1/54 (1.9%)		3/53 (5.7%)		0/54 (0%)		1/51 (2%)
Gastrointestinal disorders
Constipation	1/54 (1.9%)		5/53 (9.4%)		5/54 (9.3%)		2/51 (3.9%)
Dental caries	4/54 (7.4%)		1/53 (1.9%)		0/54 (0%)		1/51 (2%)
Diarrhoea	4/54 (7.4%)		3/53 (5.7%)		2/54 (3.7%)		3/51 (5.9%)
Gastritis	0/54 (0%)		1/53 (1.9%)		3/54 (5.6%)		0/51 (0%)
Gingivitis	1/54 (1.9%)		1/53 (1.9%)		3/54 (5.6%)		1/51 (2%)
Periodontitis	1/54 (1.9%)		0/53 (0%)		2/54 (3.7%)		3/51 (5.9%)
Stomach discomfort	3/54 (5.6%)		3/53 (5.7%)		0/54 (0%)		1/51 (2%)
Vomiting	1/54 (1.9%)		3/53 (5.7%)		0/54 (0%)		0/51 (0%)
General disorders
Malaise	5/54 (9.3%)		2/53 (3.8%)		1/54 (1.9%)		2/51 (3.9%)
Immune system disorders
Seasonal allergy	3/54 (5.6%)		0/53 (0%)		0/54 (0%)		1/51 (2%)
Infections and infestations
Bronchitis	0/54 (0%)		0/53 (0%)		3/54 (5.6%)		0/51 (0%)
Cystitis	3/54 (5.6%)		2/53 (3.8%)		2/54 (3.7%)		0/51 (0%)
Gastroenteritis	0/54 (0%)		3/53 (5.7%)		1/54 (1.9%)		2/51 (3.9%)
Herpes zoster	1/54 (1.9%)		4/53 (7.5%)		0/54 (0%)		0/51 (0%)
Hordeolum	1/54 (1.9%)		0/53 (0%)		0/54 (0%)		3/51 (5.9%)
Nasopharyngitis	21/54 (38.9%)		18/53 (34%)		22/54 (40.7%)		22/51 (43.1%)
Oral herpes	0/54 (0%)		3/53 (5.7%)		1/54 (1.9%)		0/51 (0%)
Injury, poisoning and procedural complications
Contusion	8/54 (14.8%)		1/53 (1.9%)		4/54 (7.4%)		1/51 (2%)
Joint sprain	2/54 (3.7%)		1/53 (1.9%)		1/54 (1.9%)		5/51 (9.8%)
Investigations
Gamma-glutamyltransferase increased	0/54 (0%)		0/53 (0%)		2/54 (3.7%)		3/51 (5.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/54 (0%)		4/53 (7.5%)		3/54 (5.6%)		0/51 (0%)
Back pain	4/54 (7.4%)		3/53 (5.7%)		8/54 (14.8%)		9/51 (17.6%)
Musculoskeletal pain	1/54 (1.9%)		3/53 (5.7%)		2/54 (3.7%)		1/51 (2%)
Musculoskeletal stiffness	2/54 (3.7%)		4/53 (7.5%)		1/54 (1.9%)		1/51 (2%)
Osteoarthritis	3/54 (5.6%)		0/53 (0%)		2/54 (3.7%)		2/51 (3.9%)
Pain in extremity	4/54 (7.4%)		2/53 (3.8%)		1/54 (1.9%)		2/51 (3.9%)
Periarthritis	6/54 (11.1%)		1/53 (1.9%)		1/54 (1.9%)		1/51 (2%)
Nervous system disorders
Headache	5/54 (9.3%)		7/53 (13.2%)		6/54 (11.1%)		3/51 (5.9%)
Hypoaesthesia	3/54 (5.6%)		1/53 (1.9%)		2/54 (3.7%)		5/51 (9.8%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	1/54 (1.9%)		3/53 (5.7%)		1/54 (1.9%)		1/51 (2%)
Upper respiratory tract inflammation	8/54 (14.8%)		4/53 (7.5%)		3/54 (5.6%)		6/51 (11.8%)
Skin and subcutaneous tissue disorders
Eczema	5/54 (9.3%)		6/53 (11.3%)		4/54 (7.4%)		6/51 (11.8%)
Pruritus	0/54 (0%)		0/53 (0%)		1/54 (1.9%)		3/51 (5.9%)
Vascular disorders
Hypertension	1/54 (1.9%)		2/53 (3.8%)		3/54 (5.6%)		1/51 (2%)

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.