Low Bone MassPhase 3NCT00980174
Study to Compare the Efficacy and Safety of DenosumAb Versus Placebo in Males With Osteoporosis
A Phase 3 study testing 60 mg denosumab in people with Low Bone Mass and Low Bone Mineral Density, run by Amgen.
Trial summary
The purpose of this study is to assess how effective and safe denosumab is in a population of males with low bone mass at risk of fracture. The primary clinical hypothesis is that in men with low bone mineral density, the mean percent change in lumbar spine bone mineral density at 12 months in subjects receiving… Read more about this study
- Who is it for?
- Ages 30 to 85 years, men only
- Conditions the study is for
- Low Bone Mass, Low Bone Mineral Density, Males With Osteoporosis
- What is being tested?
- 60 mg denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 242 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2009to 23 May 2012
- Phase
- Phase 3
- 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 30 to 85 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Bone Mineral Density (BMD) values (g/cm2) assessed by the local site at either the lumbar spine OR femoral neck that occur within the ranges specified in the protocol OR For subjects with a history of a major osteoporotic fracture (clinical vertebral, hip, humerus and distal radius fractures) occurring more than 6 months prior to screening, BMD values (g/cm2) assessed by the local site, at either the lumbar spine OR femoral neck that occur within the ranges specified in the protocol.
- At least 2 lumbar vertebrae, at least 1 hip and at least one forearm must be evaluable by Dual X ray Absorptiometry (DXA).
- Ambulatory males 30 to 85 years of age inclusive at the start of screening.
- Provide the appropriate written informed consent before any study specific procedure.
Who cannot join
- BMD values (g/cm2) as specified in the protocol in subjects with or without a history of major osteoporotic fractures, based on the particular scanner that is used.
- Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
- Any severe or more than 1 moderate vertebral fractures on screening spinal x ray
- Any vertebral fracture diagnosed within the 6 months prior to screening
- Any clinical fracture within the last 6 months prior to screening
- For males with a partner of childbearing potential: Subject refuses to use 2 highly effective methods of contraception for the duration of the study and for 10 months after the last dose of study medication.
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- For males with a partner who is pregnant: Subject refuses to use a condom for the duration of the study and for 10 months after the last dose of study medication.
- Previous participation in clinical trials with denosumab or administration of commercial denosumab.
- Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).
- Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (< 49.9 nmol/L)]. Vitamin D replenishment will be permitted and subjects may be re-screened; see Section 7.
- Hyper- or hypothyroidism; however, stable subjects, in the investigator's opinion, on thyroid hormone replacement therapy are allowed.
- Hyper- or hypoparathyroidism. Intact parathyroid hormone (iPTH) values outside of the reference range as determined by the central laboratory
- Elevated transaminases. Serum aspartate aminotransferase; serum glutamate-oxaloacetic transaminase > 2.5 x upper limit of normal. Serum alanine aminotransferase; serum glutamate pyruvate transaminase > 2.5 x upper limit of normal (both as determined by the central laboratory).
- Significantly impaired renal function as determined by a derived glomerular filtration rate (using the Modification of Diet in Renal Disease formula) of less than or equal to 30 mL/min/1.73 m2 calculated by the central laboratory.
- Hypo- or hypercalcemia based on the central laboratory reference ranges for albumin-adjusted serum calcium.
- Known to have tested positive for human immunodeficiency virus, hepatitis C virus, hepatitis B surface antigen or cirrhosis of the liver.
- Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma) within the last 5 years.
- Any metabolic bone disease, eg osteomalacia, osteogenesis imperfecta, rheumatoid arthritis, Paget's disease, Cushing's disease or, hyperprolactinemia which may interfere with the interpretation of the findings OR evidence of malabsorption syndromes which might interfere with absorption of vitamin D.
- Received any solid organ or bone marrow transplant or is on chronic immunosuppression for any reason.
- Any laboratory abnormality, which in the opinion of the investigator or Amgen, will prevent the subject from completing the study or interfere with the interpretation of the study results.
- Administration of intravenous bisphosphonate, or fluoride (except for dental treatment) or strontium ranelate.
- Oral bisphosphonate treatment:
- greater than or equal to 3 months cumulatively in the past 2 years, OR
- greater than or equal to 1 month in the past year, OR
- Any use during the 3-month period prior to randomization
- Administration of any of the following treatments 3 months prior to screening:
- Anabolic steroids or testosterone
- Glucocorticosteroids (greater than or equal to 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of greater than or equal to 50 mg)
- Calcitonin
- Calcitriol or vitamin D derivatives [vitamin D contained in supplements or multivitamins is allowed]
- Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin
- Chronic systemic ketoconazole, adrenocorticotrophic hormone (ACTH), cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists.
- Androgen deprivation therapy
- Known sensitivity to mammalian cell derived drug products.
- Known intolerance to calcium or vitamin D supplements.
- Height, weight or girth which may preclude accurate DXA measurements.
- Bilateral hip replacements
- Any physical or psychiatric disorder which, in the opinion of the investigator or Amgen, will prevent the subject from completing the study or interfere with the interpretation of the study results.
- Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding of or completion of the study.
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Compare the Efficacy and Safety of Denosumab Versus Placebo in Males With Low Bone Mineral Density
The purpose of this study is to assess how effective and safe denosumab is in a population of males with low bone mass at risk of fracture. The primary clinical hypothesis is that in men with low bone mineral density, the mean percent change in lumbar spine bone mineral density at 12 months in subjects receiving denosumab will be greater than in subjects receiving placebo. Denosumab is a fully human monoclonal antibody with a high affinity for Receptor Activator of Nuclear Factor (RANK) Ligand that can bind and neutralize the activity of human RANK Ligand similar to the action of endogenous osteoprotegerin.
- Conditions
- Low Bone Mass, Low Bone Mineral Density, Males With Osteoporosis, Osteopenia, Osteoporosis
- Being tested
- 60 mg denosumab, Placebo
- Keywords
- men, male, denosumab, BMD, lumbar spine, ADAMO, The ADAMO Trial, male osteoporosis, osteoporosis in men, males with low bone mineral density
- Medical subject headings
- Bone Diseases, Metabolic, Osteoporosis, Multiple Endocrine Neoplasia Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
60 mg denosumabDrug
Also called denosumab
60 mg denosumab (SC injection every 6 months)
PlaceboOther
Placebo for denosumab (SC injection every 6 months)
| Study group | Role | What they receive |
|---|---|---|
| 2 | Placebo comparator | Subjects will receive placebo for denosumab (SC injection every 6 months) for 1 year (double-blind phase) followed by 60 mg denosumab (SC injection every 6 months) for 1 year (open-label phase) Receives: Drug: 60 mg denosumab; Other: Placebo |
| 1 | Experimental | 60 mg denosumab (SC injection every 6 months) for 1 year (double-blind phase) followed by 60 mg denosumab(SC injection every 6 months) for 1 year (open-label phase). These subjects will be on denosumab for a total of 2 years. Receives: Drug: 60 mg denosumab |
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
Measured: From Baseline to 12 Months
Secondary outcomes (5)
Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
Measured: From Baseline to 12 Months
Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12
Measured: From Baseline to 12 Months
Trochanter Bone Mineral Density Percent Change From Baseline at Month 12
Measured: From Baseline to 12 Months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12
Measured: From Baseline to 12 Months
Serum Type 1 Collagen C-telopeptide (CTX) Percent Change From Baseline at Day 15
Measured: From Baseline to Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2009 (estimated)
- Study start1 Oct 2009
- Primary completion21 Jun 2011
- Study completion23 May 2012
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 (2)Papers the sponsor has linked to this study.
- Other trials for Low Bone MassStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 242 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00980174
- Sponsor's protocol ID
- 20080098
- Status last verified
- Sep 2018
- First submitted
- 17 Sep 2009
- Last updated
- 17 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Langdahl BL, Teglbjaerg CS, Ho PR, Chapurlat R, Czerwinski E, Kendler DL, Reginster JY, Kivitz A, Lewiecki EM, Miller PD, Bolognese MA, McClung MR, Bone HG, Ljunggren O, Abrahamsen B, Gruntmanis U, Yang YC, Wagman RB, Mirza F, Siddhanti S, Orwoll E. A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial. J Clin Endocrinol Metab. 2015 Apr;100(4):1335-42. doi: 10.1210/jc.2014-4079. Epub 2015 Jan 21.
PubMed 25607608Orwoll E, Teglbjaerg CS, Langdahl BL, Chapurlat R, Czerwinski E, Kendler DL, Reginster JY, Kivitz A, Lewiecki EM, Miller PD, Bolognese MA, McClung MR, Bone HG, Ljunggren O, Abrahamsen B, Gruntmanis U, Yang YC, Wagman RB, Siddhanti S, Grauer A, Hall JW, Boonen S. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab. 2012 Sep;97(9):3161-9. doi: 10.1210/jc.2012-1569. Epub 2012 Jun 21.
PubMed 22723310
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Compare the Efficacy and Safety of Denosumab Versus Placebo in Males With Low Bone Mineral Density
- ClinicalTrials.gov ID
- NCT00980174
- Acronym / sponsor ID
- 20080098
- Conditions
- Low Bone Mass, Low Bone Mineral Density, Males With Osteoporosis, Osteopenia, Osteoporosis
- Keywords
- men, male, denosumab, BMD, lumbar spine, ADAMO, The ADAMO Trial, male osteoporosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 242 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 1 Oct 2009 (actual)
- Primary completion
- 21 Jun 2011 (actual)
- Study completion
- 23 May 2012 (actual)
- First posted
- 18 Sep 2009 (estimated)
- Results
- Posted 29 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess how effective and safe denosumab is in a population of males with low bone mass at risk of fracture. The primary clinical hypothesis is that in men with low bone mineral density, the mean percent change in lumbar spine bone mineral density at 12 months in subjects receiving denosumab will be greater than in subjects receiving placebo. Denosumab is a fully human monoclonal antibody with a high affinity for Receptor Activator of Nuclear Factor (RANK) Ligand that can bind and neutralize the activity of human RANK Ligand similar to the action of endogenous osteoprotegerin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Placebo comparator | Drug: 60 mg denosumab, Other: PlaceboSubjects will receive placebo for denosumab (SC injection every 6 months) for 1 year (double-blind phase) followed by 60 mg denosumab (SC injection every 6 months) for 1 year (open-label phase) |
| 1 | Experimental | Drug: 60 mg denosumab60 mg denosumab (SC injection every 6 months) for 1 year (double-blind phase) followed by 60 mg denosumab(SC injection every 6 months) for 1 year (open-label phase). These subjects will be on denosumab for a total of 2 years. |
Who may qualify
- Ages
- 30 to 85 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Bone Mineral Density (BMD) values (g/cm2) assessed by the local site at either the lumbar spine OR femoral neck that occur within the ranges specified in the protocol OR For subjects with a history of a major osteoporotic fracture (clinical vertebral, hip, humerus and distal radius fractures) occurring more than 6 months prior to screening, BMD values (g/cm2) assessed by the local site, at either the lumbar spine OR femoral neck that occur within the ranges specified in the protocol.
- At least 2 lumbar vertebrae, at least 1 hip and at least one forearm must be evaluable by Dual X ray Absorptiometry (DXA).
- Ambulatory males 30 to 85 years of age inclusive at the start of screening.
- Provide the appropriate written informed consent before any study specific procedure.
Key exclusion criteria (39 listed)
- BMD values (g/cm2) as specified in the protocol in subjects with or without a history of major osteoporotic fractures, based on the particular scanner that is used.
- Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
- Any severe or more than 1 moderate vertebral fractures on screening spinal x ray
- Any vertebral fracture diagnosed within the 6 months prior to screening
- Any clinical fracture within the last 6 months prior to screening
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 |
|---|---|---|
| 60 mg denosumabAlso: denosumab60 mg denosumab (SC injection every 6 months) | Drug | 1, 2 |
| PlaceboPlacebo for denosumab (SC injection every 6 months) | Other | 2 |
Primary outcome
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: From Baseline to 12 Months
5 secondary outcomes
Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: From Baseline to 12 Months
Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: From Baseline to 12 Months
Trochanter Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: From Baseline to 12 Months
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: From Baseline to 12 Months
Serum Type 1 Collagen C-telopeptide (CTX) Percent Change From Baseline at Day 15
Time frame: From Baseline to Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25607608Langdahl BL, Teglbjaerg CS, Ho PR, Chapurlat R, Czerwinski E, Kendler DL, Reginster JY, Kivitz A, Lewiecki EM, Miller PD, Bolognese MA, McClung MR, Bone HG, Ljunggren O, Abrahamsen B, Gruntmanis U, Yang YC, Wagman RB, Mirza F, Siddhanti S, Orwoll E. A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial. J Clin Endocrinol Metab. 2015 Apr;100(4):1335-42. doi: 10.1210/jc.2014-4079. Epub 2015 Jan 21.
- Background: PubMed 22723310Orwoll E, Teglbjaerg CS, Langdahl BL, Chapurlat R, Czerwinski E, Kendler DL, Reginster JY, Kivitz A, Lewiecki EM, Miller PD, Bolognese MA, McClung MR, Bone HG, Ljunggren O, Abrahamsen B, Gruntmanis U, Yang YC, Wagman RB, Siddhanti S, Grauer A, Hall JW, Boonen S. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab. 2012 Sep;97(9):3161-9. doi: 10.1210/jc.2012-1569. Epub 2012 Jun 21.
- 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 3 study testing 60 mg denosumab in people with Low Bone Mass and 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 4 inclusion and 39 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 17 Oct 2018. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 29 Nov 2012). 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 (time frame: From Baseline to 12 Months). 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 NCT00980174, which also lists 2 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 17 Oct 2018.