Study of Transitioning From Alendronate to Denosumab

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00377819
• Collaborator: (none)
• Enrollment: 504
• Arms: 2
• Duration (Months): 22

Study Details

Study Description

Brief Summary

The study will evaluate the efficacy and safety of transitioning postmenopausal women on current alendronate therapy to denosumab. Endpoints studied will include bone mineral density, bone turnover markers and bone histology in a subset of subjects.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: alendronate; Drug: Denosumab (AMG 162)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 504 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Study to Evaluate Safety and Efficacy of Transitioning Therapy From Alendronate to Denosumab (AMG 162) in Postmenopausal Women With Low Bone Mineral Density
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: denosumab	Drug: Denosumab (AMG 162); 60 mg SC q 6 mos
Active Comparator: alendronate	Drug: alendronate; 70 mg oral QW

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Total Hip Bone Mineral Density [Baseline, 12 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change calculated using [(12 month value - baseline value) / baseline value]*100.

Secondary Outcome Measures

1. Percent Change From Baseline in Lumbar Spine Bone Mineral Density [Baseline, 12 months]

   Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change calculated using [(12 month value - baseline value) / baseline value]*100.

2. Percent Change From Baseline in Serum C-Telopeptide-I (CTX-I) [Baseline, 3 months]

   Percent Change From Baseline to Month 3 in Serum CTX-I. Percent change calculated using [(3 month value - baseline value) / baseline value]*100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Postmenopausal females 55 yrs or older

• Received alendronate therapy for osteoporosis for at least 6 months prior to entry into study

• Lumbar spine or total hip Bone Mineral Density (BMD) corresponding to T-score ≤ -2 and ≥ -4

Exclusion Criteria:

• Vitamin D deficiency

• Administration of intravenous bisphosphonate, or

• fluoride (except for dental treatment) or

• strontium ranelate

• Administration of Parathyroid Hormone (PTH) or Parathyroid Hormone (PTH) derivatives (eg; teriparatide) within the last year

• Administration of any bisphosphonate other than alendronate (ALN) within 1 year of screening

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:

• Notice regarding posted summaries of trial results
• AmgenTrials clinical trials website

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00377819
• Other Study ID Numbers: 20050234
• First Posted: Sep 18, 2006
• Last Update Posted: Jul 11, 2011
• Last Verified: Jun 1, 2011

• Keywords provided by , ,: RANKL; RANK; denosumab; AMG 162; osteoporosis; bone turnover; bone mineral density; clinical trial; postmenopausal osteoporosis; alendronate; total hip bone mineral density
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Denosumab; Alendronate

Study Results

Participant Flow

Recruitment Details	First Subject Enrolled: 02-Oct-2006 Last Subject Enrolled: 07-Mar-2007

Arm/Group Title	Alendronate 70 mg QW	Denosumab 60 mg Q6M
Arm/Group Description	70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally
Period Title: Overall Study
STARTED	251	253
Received Study Medication	249	253
COMPLETED	238	243
NOT COMPLETED	13	10

Baseline Characteristics

Arm/Group Title	Alendronate 70 mg QW	Denosumab 60 mg Q6M	Total
Arm/Group Description	70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally	Total of all reporting groups
Overall Participants	251	253	504
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.2 (7.7)	66.9 (7.8)	67.6 (7.8)
Sex: Female, Male (Count of Participants)
Female	251 100%	253 100%	504 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
White or Caucasian	232 92.4%	238 94.1%	470 93.3%
Black or African American	2 0.8%	0 0%	2 0.4%
Hispanic or Latino	12 4.8%	11 4.3%	23 4.6%
Asian	1 0.4%	1 0.4%	2 0.4%
Japanese	1 0.4%	3 1.2%	4 0.8%
American Indian or Alaska Native	1 0.4%	0 0%	1 0.2%
Native Hawaiian or Other Pacific Islander	1 0.4%	0 0%	1 0.2%
Other	1 0.4%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Total Hip Bone Mineral Density
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change calculated using [(12 month value - baseline value) / baseline value]*100.
Time Frame	Baseline, 12 months

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline evaluation and at least 1 non-missing post-baseline evaluation.

Arm/Group Title	Alendronate 70 mg QW	Denosumab 60 mg Q6M
Arm/Group Description	70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally
Measure Participants	233	241
Least Squares Mean (95% Confidence Interval) [Percent Change]	1.05	1.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alendronate 70 mg QW, Denosumab 60 mg Q6M
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin = -0.35%
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.85
	Confidence Interval	() 95%; 0.44 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on repeated measures model adjusting for treatment, length of prior alendronate stratification variable, visit, baseline value, machine type, treatment by visit interaction, and baseline value by machine type interaction

2. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Mineral Density
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change calculated using [(12 month value - baseline value) / baseline value]*100.
Time Frame	Baseline, 12 months

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline evaluation and at least 1 non-missing post-baseline evaluation.

Arm/Group Title	Alendronate 70 mg QW	Denosumab 60 mg Q6M
Arm/Group Description	70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally
Measure Participants	235	242
Least Squares Mean (95% Confidence Interval) [Percent Change]	1.85	3.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alendronate 70 mg QW, Denosumab 60 mg Q6M
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin = -0.22%
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.18
	Confidence Interval	() 95%; 0.63 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on repeated measures model adjusting for treatment, length of prior alendronate stratification variable, visit, baseline value, machine type, treatment by visit interaction, and baseline value by machine type interaction

3. Secondary Outcome

Title	Percent Change From Baseline in Serum C-Telopeptide-I (CTX-I)
Description	Percent Change From Baseline to Month 3 in Serum CTX-I. Percent change calculated using [(3 month value - baseline value) / baseline value]*100.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline evaluation and non-missing post-baseline evaluation at month 3.

Arm/Group Title	Alendronate 70 mg QW	Denosumab 60 mg Q6M
Arm/Group Description	70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally
Measure Participants	240	245
Median (Inter-Quartile Range) [Percent Change]	-4.2	-63.3

Statistical Analysis 1

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	<0.0001
	Comments
	Method	Van Elteren Stratified Rank Test
	Comments

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Alendronate 70 mg QW		Denosumab 60 mg Q6M
Arm/Group Description
All Cause Mortality
	Alendronate 70 mg QW		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Alendronate 70 mg QW		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/249 (6.4%)		15/253 (5.9%)
Cardiac disorders
Angina pectoris	1/249 (0.4%)		1/253 (0.4%)
Atrial fibrillation	1/249 (0.4%)		0/253 (0%)
Atrial flutter	0/249 (0%)		1/253 (0.4%)
Sick sinus syndrome	0/249 (0%)		1/253 (0.4%)
Gastrointestinal disorders
Appendicitis perforated	1/249 (0.4%)		0/253 (0%)
Haemorrhoids	0/249 (0%)		1/253 (0.4%)
Loose tooth	1/249 (0.4%)		0/253 (0%)
Nausea	1/249 (0.4%)		0/253 (0%)
Pancreatitis	1/249 (0.4%)		0/253 (0%)
Vomiting	1/249 (0.4%)		0/253 (0%)
General disorders
Hyperpyrexia	1/249 (0.4%)		0/253 (0%)
Inflammation	0/249 (0%)		1/253 (0.4%)
Non-cardiac chest pain	1/249 (0.4%)		0/253 (0%)
Hepatobiliary disorders
Cholelithiasis	0/249 (0%)		1/253 (0.4%)
Immune system disorders
Anaphylactic reaction	1/249 (0.4%)		0/253 (0%)
Infections and infestations
Bacteraemia	1/249 (0.4%)		0/253 (0%)
Diverticulitis	0/249 (0%)		1/253 (0.4%)
Gingival infection	1/249 (0.4%)		0/253 (0%)
Lobar pneumonia	1/249 (0.4%)		0/253 (0%)
Periodontal infection	1/249 (0.4%)		0/253 (0%)
Injury, poisoning and procedural complications
Foot fracture	0/249 (0%)		1/253 (0.4%)
Head injury	1/249 (0.4%)		0/253 (0%)
Tooth fracture	2/249 (0.8%)		0/253 (0%)
Wrist fracture	0/249 (0%)		1/253 (0.4%)
Musculoskeletal and connective tissue disorders
Synovitis	0/249 (0%)		1/253 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ameloblastoma	0/249 (0%)		1/253 (0.4%)
Breast cancer	2/249 (0.8%)		0/253 (0%)
Lung neoplasm malignant	0/249 (0%)		1/253 (0.4%)
Nodular fasciitis	1/249 (0.4%)		0/253 (0%)
Rectal cancer	0/249 (0%)		1/253 (0.4%)
Nervous system disorders
Carotid artery stenosis	0/249 (0%)		1/253 (0.4%)
Cerebrovascular accident	1/249 (0.4%)		1/253 (0.4%)
Reproductive system and breast disorders
Cystocele	0/249 (0%)		1/253 (0.4%)
Uterine prolapse	1/249 (0.4%)		1/253 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	0/249 (0%)		1/253 (0.4%)
Vascular disorders
Hypertension	0/249 (0%)		1/253 (0.4%)
Other (Not Including Serious) Adverse Events
	Alendronate 70 mg QW		Denosumab 60 mg Q6M
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	101/249 (40.6%)		103/253 (40.7%)
Gastrointestinal disorders
Constipation	12/249 (4.8%)		13/253 (5.1%)
Infections and infestations
Bronchitis	14/249 (5.6%)		16/253 (6.3%)
Nasopharyngitis	27/249 (10.8%)		34/253 (13.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	26/249 (10.4%)		15/253 (5.9%)
Back pain	29/249 (11.6%)		27/253 (10.7%)
Osteoarthritis	13/249 (5.2%)		11/253 (4.3%)
Pain in extremity	21/249 (8.4%)		12/253 (4.7%)

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.