Low Bone Mineral DensityPhase 2NCT00043186

Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

A Phase 2 study testing Denosumab and Alendronate in people with Low Bone Mineral Density, run by Amgen.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

To determine the effect of denosumab treatment compared with placebo over 12 months on bone mineral density (BMD) of the lumbar spine in postmenopausal women with low BMD. The clinical hypothesis is that denosumab subcutaneous injections administered every 3 or 6 months for 12 months will significantly increase lumbar… Read more about this study

Who is it for?: Ages Up to 80 years, women only
Conditions the study is for: Low Bone Mineral Density
What is being tested?: Denosumab and Alendronate
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 412 participants
Where: No sites listed yet
Study dates: May 2002to Jun 2007
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 80 years
Women only
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

women not more than 80 years of age on date of randomization
≥ 1 year postmenopausal on date of randomization
ambulatory
if ≤ 60 years of age, or had or would require a bilateral oophorectomy, serum follicle stimulating hormone (FSH) > 50 mU/mL or serum estradiol < 20 pg/mL
low BMD (BMD T-score ≤ -1.8 at any 1 of the following sites: lumbar spine, femoral neck, or total hip; BMD T-scores must not have been < -4.0 at the lumbar spine or - 3.5 at the femoral neck or total hip)
before any study-specific procedure, including the screening dual X-ray absorptiometry (DXA) scan, gave informed consent for participation in the study.

Who cannot join

fluoride treatment for osteoporosis within the 2 years before the enrollment date
bisphosphonate use within the 12 months before the enrollment date
administration of the following medications within the 6 months before the enrollment date
tibolone
Parathyroid hormone (PTH) (or any derivative)
systemic glucocorticosteroids (> 5 mg oral prednisone equivalent per day for > 10 days)

Show all 36Show fewer

inhaled corticosteroids (> 2000 μg per day for > 10 days)
anabolic steroids or testosterone
administration of the following medications within the 3 months before the enrollment date
systemic hormone replacement therapy
selective estrogen receptor modulators
calcitonin
calcitriol
current hyper- or hypothyroidism (allowed if stable on thyroid replacement therapy and thyroid-stimulating hormone was within the normal range)
current hyper- or hypoparathyroidism
albumin-adjusted serum calcium < 8.5 mg/dL (< 2.125 mol/L)
osteomalacia
rheumatoid arthritis
Paget's disease
malignancy within the 5 years before enrollment (except cervical carcinoma in situ or basal cell carcinoma, which were acceptable)
renal disease; ie, creatinine clearance ≤ 35 mL/min
any bone disease, other than osteoporosis, which could interfere with the interpretation of the findings (eg, osteogenesis imperfecta or osteopetrosis)
malabsorption syndrome
weight, height, or girth that could preclude accurate DXA measurements
< 2 lumbar vertebrae (L1 through L4) evaluable by DXA
recent long bone fracture (within 6 months)
osteoporotic-related fracture (ie, crush or wedge vertebral fracture or hip fracture) known or suspected to have occurred within 2 years of randomization
> 1 single, grade 1 vertebral fracture
currently enrolled in or had participated within the previous 30 days in other investigational device or drug trial(s) (For some trials, this may have been allowed after discussion and written approval from Amgen.)
known sensitivity to mammalian-derived drug preparations (eg, Herceptin®)
any organic or psychiatric disorder, serum chemistry, or hematology that, in the opinion of the investigator, could have prevented the subject from completing the study or have interfered with the interpretation of the study results
self-reported alcohol or drug abuse within the previous 12 months
any disorder that compromised the ability to give truly informed consent for participation in the study
previous administration of denosumab
known sensitivity or contraindication to alendronate
known sensitivity or contraindication to tetracycline derivatives (subjects in the biopsy substudy only).

About this study

Official title: A Randomized, Double-Blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 162 in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Conditions: Low Bone Mineral Density
Being tested: Placebo, Denosumab, Alendronate
Keywords: bone loss, osteoporosis
Medical subject headings: Bone Diseases, Metabolic, Osteoporosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Placebo subcutaneous injection
DenosumabDrug
Also called AMG 162, Prolia
Denosumab for subcutaneous injection
AlendronateDrug
Also called Fosamax
Alendronate 70 mg tablets

Study groups in NCT00043186
Study group	Role	What they receive
Placebo	Placebo comparator	Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Receives: Drug: Placebo
Denosumab 6 mg every 3 months	Experimental	Participants received denosumab 6 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Receives: Drug: Denosumab
Denosumab 14 mg every 3 months	Experimental	Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Receives: Drug: Denosumab
Denosumab 30 mg every 3 months	Experimental	Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Receives: Drug: Denosumab
Denosumab 14 mg every 6 months	Experimental	Participants received denosumab 14 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Receives: Drug: Denosumab
Denosumab 60 mg every 6 months	Experimental	Participants received denosumab 60 mg SC every 6 months until Month 42. Receives: Drug: Denosumab
Denosumab 100 mg every 6 months	Experimental	Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Receives: Drug: Denosumab
Denosumab 210 mg every 6 months	Experimental	Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Receives: Drug: Denosumab
Alendronate 70 mg	Active comparator	Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment. Receives: Drug: Alendronate

What is being measured

The primary outcome is the main question the study is designed to answer.

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and Month 12

Secondary outcomes (35)

Serum CTX Percent Change From Baseline at Month 12
Serum C-Telopeptide (CTX). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and Month 12
Urine NTX/Creatinine Percent Change From Baseline at Month 12
Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and Month 12
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and Month 12
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 24 months
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 36 months
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 42 months
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 48 months
Serum CTX Percent Change From Baseline at Month 24
Serum C-Telopeptide (CTX). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 24 months
Serum CTX Percent Change From Baseline at Month 36
Serum C-Telopeptide (CTX). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 36 months
Serum CTX Percent Change From Baseline at Month 42
Serum C-Telopeptide (CTX). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 42 months
Serum CTX Percent Change From Baseline at Month 48
Serum C-Telopeptide (CTX). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 48 months
Urine NTX/Creatinine Percent Change From Baseline at Month 24
Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 24 months
Urine NTX/Creatinine Percent Change From Baseline at Month 36
Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 36 months
Urine NTX/Creatinine Percent Change From Baseline at Month 42
Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 42 months
Urine NTX/Creatinine Percent Change From Baseline at Month 48
Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 48 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 12 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 24
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 24 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 36
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 36 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 42
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 42 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 48
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 48 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 12 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 24 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 36 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 42 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 48 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 12 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 24
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 24 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 36
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 36 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 42
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 42 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 48
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 48 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12
Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 12 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24
Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 24 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36
Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 36 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42
Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 42 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48
Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Measured: Baseline and 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2002Jun 2007

First posted7 Aug 2002 (estimated)
Study startMay 2002
Primary completionApr 2007
Study completionJun 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Low Bone Mineral DensityStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 412 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00043186
Sponsor's protocol ID: 20010223
Status last verified: Sep 2013
First submitted: 6 Aug 2002
Last updated: 18 Sep 2013
Results posted: Yes, on ClinicalTrials.gov

Publications

Beck TJ, Lewiecki EM, Miller PD, Felsenberg D, Liu Y, Ding B, Libanati C. Effects of denosumab on the geometry of the proximal femur in postmenopausal women in comparison with alendronate. J Clin Densitom. 2008 Jul-Sep;11(3):351-9. doi: 10.1016/j.jocd.2008.04.001. Epub 2008 May 20.
PubMed 18495508
Lewiecki EM, Miller PD, McClung MR, Cohen SB, Bolognese MA, Liu Y, Wang A, Siddhanti S, Fitzpatrick LA; AMG 162 Bone Loss Study Group. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res. 2007 Dec;22(12):1832-41. doi: 10.1359/jbmr.070809.
PubMed 17708711
McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ; AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006 Feb 23;354(8):821-31. doi: 10.1056/NEJMoa044459.
PubMed 16495394
Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.
PubMed 18539106
Peterson MC, Riggs MM. A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling. Bone. 2010 Jan;46(1):49-63. doi: 10.1016/j.bone.2009.08.053. Epub 2009 Sep 2.
PubMed 19732857

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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CFTR Modulator Effects on Bone and Muscle in Adults With Cystic Fibrosis
Cystic Fibrosis, Bone Loss
Active, not recruiting
AI-Supported Mobile High-Impact and Strengthening Exercise Program in Postmenopausal Women With Low Bone Density
Osteopenia
Active, not recruiting
L-PRF Block vs Composite Graft for Horizontal Ridge Augmentation
Alveolar Ridge Resorption After Extraction, Alveolar Bone Loss
RecruitingObservational study
Observational Study of Bone Complications in People With Post-menopausal Breast Cancer Who Have Stopped Treatment With Denosumab and Aromatase Inhibitors
Breast Cancer

All Low Bone Mineral Density trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 162 in the Treatment of Postmenopausal Women With Low Bone Mineral Density
ClinicalTrials.gov ID: NCT00043186
Acronym / sponsor ID: 20010223
Conditions: Low Bone Mineral Density
Keywords: bone loss, osteoporosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 412 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: May 2002
Primary completion: Apr 2007 (actual)
Study completion: Jun 2007 (actual)
First posted: 7 Aug 2002 (estimated)
Results: Posted 28 Jul 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 9

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboParticipants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42.
Denosumab 6 mg every 3 months	Experimental	Drug: DenosumabParticipants received denosumab 6 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 14 mg every 3 months	Experimental	Drug: DenosumabParticipants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 30 mg every 3 months	Experimental	Drug: DenosumabParticipants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42.
Denosumab 14 mg every 6 months	Experimental	Drug: DenosumabParticipants received denosumab 14 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 60 mg every 6 months	Experimental	Drug: DenosumabParticipants received denosumab 60 mg SC every 6 months until Month 42.
Denosumab 100 mg every 6 months	Experimental	Drug: DenosumabParticipants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.
Denosumab 210 mg every 6 months	Experimental	Drug: DenosumabParticipants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.
Alendronate 70 mg	Active comparator	Drug: AlendronateParticipants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.

Who may qualify

Ages: Up to 80 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (6 listed)

women not more than 80 years of age on date of randomization
≥ 1 year postmenopausal on date of randomization
ambulatory
if ≤ 60 years of age, or had or would require a bilateral oophorectomy, serum follicle stimulating hormone (FSH) > 50 mU/mL or serum estradiol < 20 pg/mL
low BMD (BMD T-score ≤ -1.8 at any 1 of the following sites: lumbar spine, femoral neck, or total hip; BMD T-scores must not have been < -4.0 at the lumbar spine or - 3.5 at the femoral neck or total hip)

Key exclusion criteria (36 listed)

fluoride treatment for osteoporosis within the 2 years before the enrollment date
bisphosphonate use within the 12 months before the enrollment date
administration of the following medications within the 6 months before the enrollment date
administration of the following medications within the 3 months before the enrollment date
current hyper- or hypothyroidism (allowed if stable on thyroid replacement therapy and thyroid-stimulating hormone was within the normal range)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboPlacebo subcutaneous injection	Drug	Placebo
DenosumabAlso: AMG 162, ProliaDenosumab for subcutaneous injection	Drug	Denosumab 100 mg every 6 months, Denosumab 14 mg every 3 months, Denosumab 14 mg every 6 months, Denosumab 210 mg every 6 months, Denosumab 30 mg every 3 months, Denosumab 6 mg every 3 months, Denosumab 60 mg every 6 months
AlendronateAlso: FosamaxAlendronate 70 mg tablets	Drug	Alendronate 70 mg

Primary outcome

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms
Time frame: Baseline and Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

35 secondary outcomes

Serum CTX Percent Change From Baseline at Month 12
Time frame: Baseline and Month 12
Urine NTX/Creatinine Percent Change From Baseline at Month 12
Time frame: Baseline and Month 12
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm
Time frame: Baseline and Month 12
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24
Time frame: Baseline and 24 months
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36
Time frame: Baseline and 36 months
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42
Time frame: Baseline and 42 months
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48
Time frame: Baseline and 48 months
Serum CTX Percent Change From Baseline at Month 24
Time frame: Baseline and 24 months
Serum CTX Percent Change From Baseline at Month 36
Time frame: Baseline and 36 months
Serum CTX Percent Change From Baseline at Month 42
Time frame: Baseline and 42 months
Serum CTX Percent Change From Baseline at Month 48
Time frame: Baseline and 48 months
Urine NTX/Creatinine Percent Change From Baseline at Month 24
Time frame: Baseline and 24 months
Urine NTX/Creatinine Percent Change From Baseline at Month 36
Time frame: Baseline and 36 months
Urine NTX/Creatinine Percent Change From Baseline at Month 42
Time frame: Baseline and 42 months
Urine NTX/Creatinine Percent Change From Baseline at Month 48
Time frame: Baseline and 48 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: Baseline and 12 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 24
Time frame: Baseline and 24 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 36
Time frame: Baseline and 36 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 42
Time frame: Baseline and 42 months
Total Hip Bone Mineral Density Percent Change From Baseline at Month 48
Time frame: Baseline and 48 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: Baseline and 12 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24
Time frame: Baseline and 24 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36
Time frame: Baseline and 36 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42
Time frame: Baseline and 42 months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48
Time frame: Baseline and 48 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: Baseline and 12 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 24
Time frame: Baseline and 24 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 36
Time frame: Baseline and 36 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 42
Time frame: Baseline and 42 months
Total Body Bone Mineral Density Percent Change From Baseline at Month 48
Time frame: Baseline and 48 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12
Time frame: Baseline and 12 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24
Time frame: Baseline and 24 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36
Time frame: Baseline and 36 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42
Time frame: Baseline and 42 months
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48
Time frame: Baseline and 48 months

Results and safety

Results posted to the registry on 28 Jul 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	46	29
Denosumab 6 mg Q3M	44	29
Denosumab 14 mg Q3M	44	24
Denosumab 30 mg Q3M	41	19
Denosumab 14 mg Q6M	54	36
Denosumab 60 mg Q6M	47	39
Denosumab 100 mg Q6M	42	25
Denosumab 210 mg Q6M	47	31
Alendronate 70 mg	47	30

Primary outcome: Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms

Time frame: Baseline and Month 12. Least squares mean (Standard Error). Unit: Percent change

Measure	Placebo n = 40	Denosumab 6 mg Q3M n = 36	Denosumab 14 mg Q3M n = 36	Denosumab 30 mg Q3M n = 32	Denosumab 14 mg Q6M n = 48	Denosumab 60 mg Q6M n = 41	Denosumab 100 mg Q6M n = 37	Denosumab 210 mg Q6M n = 41
Value	-0.81 (0.48)	4.41 (0.50)	4.71 (0.50)	6.69 (0.54)	3.03 (0.43)	4.55 (0.47)	5.52 (0.49)	5.07 (0.47)

Placebo vs Denosumab 210 mg Q6M: Mean Difference (Final Values): 5.87 (95% CI 4.59 to 7.16), p <0.001, ANCOVA
Placebo vs Denosumab 100 mg Q6M: Mean Difference (Final Values): 6.33 (95% CI 5.01 to 7.65), p <0.001, ANCOVA
Placebo vs Denosumab 60 mg Q6M: Mean Difference (Final Values): 5.35 (95% CI 4.07 to 6.64), p <0.001, ANCOVA

Population analysed: Randomized participants with non-missing Baseline and non-missing value at Month 12.

35 secondary outcomes are reported in the full results.

Adverse events

Time frame: 48 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	5 of 46 (10.9%)	43 of 46 (93.5%)	Not reported
Denosumab 6 mg Q3M	7 of 43 (16.3%)	38 of 43 (88.4%)	Not reported
Denosumab 14 mg Q3M	13 of 44 (29.5%)	39 of 44 (88.6%)	Not reported
Denosumab 30 mg Q3M	9 of 40 (22.5%)	35 of 40 (87.5%)	Not reported
Denosumab 14 mg Q6M	7 of 53 (13.2%)	44 of 53 (83%)	Not reported
Denosumab 60 mg Q6M	5 of 47 (10.6%)	42 of 47 (89.4%)	Not reported
Denosumab 100 mg Q6M	9 of 41 (22%)	38 of 41 (92.7%)	Not reported
Denosumab 210 mg Q6M	6 of 46 (13%)	41 of 46 (89.1%)	Not reported
Alendronate 70 mg	8 of 46 (17.4%)	42 of 46 (91.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 18495508Beck TJ, Lewiecki EM, Miller PD, Felsenberg D, Liu Y, Ding B, Libanati C. Effects of denosumab on the geometry of the proximal femur in postmenopausal women in comparison with alendronate. J Clin Densitom. 2008 Jul-Sep;11(3):351-9. doi: 10.1016/j.jocd.2008.04.001. Epub 2008 May 20.
Results publication: PubMed 17708711Lewiecki EM, Miller PD, McClung MR, Cohen SB, Bolognese MA, Liu Y, Wang A, Siddhanti S, Fitzpatrick LA; AMG 162 Bone Loss Study Group. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res. 2007 Dec;22(12):1832-41. doi: 10.1359/jbmr.070809.
Results publication: PubMed 16495394McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ; AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006 Feb 23;354(8):821-31. doi: 10.1056/NEJMoa044459.
Results publication: PubMed 18539106Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.
Results publication: PubMed 19732857Peterson MC, Riggs MM. A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling. Bone. 2010 Jan;46(1):49-63. doi: 10.1016/j.bone.2009.08.053. Epub 2009 Sep 2.
AmgenTrials clinical trials websiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Denosumab and Alendronate in people with Low Bone Mineral Density, run by Amgen.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jul 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms (time frame: Baseline and Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00043186, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2013.