Trial Outcomes & Findings for Study of Transitioning From Alendronate to Denosumab (NCT NCT00377819)

Last Updated: 2011-07-11

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

504 participants

Primary outcome timeframe

Baseline, 12 months

Results posted on

2011-07-11

Participant Flow

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

Participant milestones

Participant milestones
Measure	Alendronate 70 mg QW 70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	Denosumab 60 mg Q6M 60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally
Overall Study STARTED	251	253
Overall Study Received Study Medication	249	253
Overall Study COMPLETED	238	243
Overall Study NOT COMPLETED	13	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Alendronate 70 mg QW 70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	Denosumab 60 mg Q6M 60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally
Overall Study Adverse Event	2	3
Overall Study Withdrawal by Subject	10	4
Overall Study Death	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Protocol Violation	1	1

Baseline Characteristics

Study of Transitioning From Alendronate to Denosumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alendronate 70 mg QW n=251 Participants 70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	Denosumab 60 mg Q6M n=253 Participants 60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally	Total n=504 Participants Total of all reporting groups
Age Continuous	68.2 Years STANDARD_DEVIATION 7.7 • n=5 Participants	66.9 Years STANDARD_DEVIATION 7.8 • n=7 Participants	67.6 Years STANDARD_DEVIATION 7.8 • n=5 Participants
Sex: Female, Male Female	251 Participants n=5 Participants	253 Participants n=7 Participants	504 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	232 Participants n=5 Participants	238 Participants n=7 Participants	470 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 12 months

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

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

Outcome measures

Outcome measures
Measure	Alendronate 70 mg QW n=233 Participants 70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	Denosumab 60 mg Q6M n=241 Participants 60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally
Percent Change From Baseline in Total Hip Bone Mineral Density	1.05 Percent Change Interval 0.76 to 1.34	1.9 Percent Change Interval 1.61 to 2.18

SECONDARY outcome

Timeframe: Baseline, 12 months

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

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

Outcome measures

Outcome measures
Measure	Alendronate 70 mg QW n=235 Participants 70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	Denosumab 60 mg Q6M n=242 Participants 60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally
Percent Change From Baseline in Lumbar Spine Bone Mineral Density	1.85 Percent Change Interval 1.44 to 2.26	3.03 Percent Change Interval 2.63 to 3.44

SECONDARY outcome

Timeframe: Baseline, 3 months

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

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

Outcome measures

Outcome measures
Measure	Alendronate 70 mg QW n=240 Participants 70 mg alendronate once weekly (QW) orally plus placebo for denosumab subcutaneously once every 6 months (Q6M)	Denosumab 60 mg Q6M n=245 Participants 60 mg denosumab administered subcutaneously once every 6 months (Q6M) plus placebo for alendronate once weekly (QW) orally
Percent Change From Baseline in Serum C-Telopeptide-I (CTX-I)	-4.2 Percent Change Interval -29.4 to 25.1	-63.3 Percent Change Interval -78.5 to -38.0

Adverse Events

Alendronate 70 mg QW

Serious events: 16 serious events

Other events: 101 other events

Deaths: 0 deaths

Denosumab 60 mg Q6M

Serious events: 15 serious events

Other events: 103 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Alendronate 70 mg QW n=249 participants at risk	Denosumab 60 mg Q6M n=253 participants at risk
Gastrointestinal disorders Constipation	4.8% 12/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.1% 13/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Bronchitis	5.6% 14/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.3% 16/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Nasopharyngitis	10.8% 27/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	13.4% 34/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	10.4% 26/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.9% 15/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	11.6% 29/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.7% 27/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Osteoarthritis	5.2% 13/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.3% 11/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	8.4% 21/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.7% 12/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Alendronate 70 mg QW n=249 participants at risk	Denosumab 60 mg Q6M n=253 participants at risk
Cardiac disorders Angina pectoris	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Atrial fibrillation	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Atrial flutter	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Sick sinus syndrome	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Appendicitis perforated	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Haemorrhoids	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Loose tooth	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Nausea	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Pancreatitis	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Vomiting	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Hyperpyrexia	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Inflammation	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Non-cardiac chest pain	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Hepatobiliary disorders Cholelithiasis	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Immune system disorders Anaphylactic reaction	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Bacteraemia	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Diverticulitis	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Gingival infection	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Lobar pneumonia	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Periodontal infection	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Head injury	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Tooth fracture	0.80% 2/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Synovitis	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ameloblastoma	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.80% 2/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nodular fasciitis	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Carotid artery stenosis	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Cerebrovascular accident	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Reproductive system and breast disorders Cystocele	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Reproductive system and breast disorders Uterine prolapse	0.40% 1/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Hypertension	0.00% 0/249 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.40% 1/253 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.