OsteoporosisPhase 3DIRECTNCT00680953

Denosumab Fracture Intervention Randomized Placebo Controlled Trial in Japanese Patients With Osteoporosis

A Phase 3 study testing Denosumab and Alendronate sodium hydrate in people with Osteoporosis, run by Daiichi Sankyo Co., Ltd. at 4 sites in Japan.

Completed

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

Official record

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Trial summary

Evaluate the efficacy and safety of denosumab in the treatment of involutional (postmenopausal and senile) osteoporotic subjects with prevalent fragility vertebral fracture(s) Read more about this study

Who is it for?: Ages 50 years and older
Conditions the study is for: Osteoporosis
What is being tested?: Denosumab and Alendronate sodium hydrate
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: 1,262 participants
Where: 4 sitesJapan
Study dates: May 2008to Jul 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 50 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Involutional (postmenopausal and senile) osteoporosis with prevalent fragility vertebral fractures

Who cannot join

Any underlying condition,(other than BMD) that might have resulted in abnormal bone metabolism

Trial locations and contacts

4 sites in 1 country.

Japan4 sites

Study site
Fukuoka
Study site
Osaka
Study site
Sapporo
Study site
Tokyo

Other trials in Japan

About this study

Official title: A Randomized, Double-Blind, Placebo-controlled Phase 3 Study Evaluating Efficacy and Safety of Denosumab in Japanese Osteoporotic Subjects With Prevalent Fragility Vertebral Fracture(s)

Evaluate the efficacy and safety of denosumab in the treatment of involutional (postmenopausal and senile) osteoporotic subjects with prevalent fragility vertebral fracture(s)

Conditions: Osteoporosis
Being tested: Denosumab, Placebo, Alendronate sodium hydrate
Medical subject headings: Osteoporosis

What participants receive

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

DenosumabDrug
Subcutaneous injection every 6 months for 24 months, followed by a 12-month period of denosumab (subcutaneously - every six months).
PlaceboDrug
Subcutaneous injection every 6 months for 24 months, followed by a 12-month period of denosumab (subcutaneously - every six months).
Alendronate sodium hydrateDrug
Oral tablet once a week for 24 months

Study groups in NCT00680953
Study group	Role	What they receive
1	Experimental	Denosumab (subcutaneously - every 6 months) + daily calcium and vitamin D supplements for 24 months, followed by a 12-month period of denosumab (subcutaneously - every 6 months). Receives: Drug: Denosumab
2	Placebo comparator	Placebo (subcutaneously every 6 months) + daily calcium and vitamin D supplements for 24 months, followed by a 12-month period of denosumab (subcutaneously - every 6 months). Receives: Drug: Placebo
3	Active comparator	Alendronate sodium hydrate oral tablets weekly + daily calcium and vitamin D supplements for 24 months (open label reference arm). Receives: Drug: Alendronate sodium hydrate

What is being measured

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

Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo
Measured: Baseline to 24 months

Secondary outcomes (2)

The Percentage of Non-vertebral Fractures
The results are expressed as percentage by Kaplan-Meier estimate the percentage of participants with non-vertebral fractures
Measured: Baseline to 24 Months
Percentage of Participants With Hip Fractures in Osteoporotic Participants Treated With Denosumab Compared to Treatment With Placebo.
The results are expressed as a percentage by Kaplan-Meier estimate.
Measured: Baseline to 24 Months

Timeline

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

May 2008Jul 2012

First posted20 May 2008 (estimated)
Study startMay 2008
Primary completionJun 2012
Study completionJul 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 (3)Papers the sponsor has linked to this study.
Other trials for OsteoporosisStudies of the same condition, open and under way.
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: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 1,262 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00680953
Sponsor's protocol ID: AMG162-A-J301
Acronym: DIRECT
Status last verified: Feb 2015
First submitted: 16 May 2008
Last updated: 12 Mar 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Nakamura T, Matsumoto T, Sugimoto T, Hosoi T, Miki T, Gorai I, Yoshikawa H, Tanaka Y, Tanaka S, Sone T, Nakano T, Ito M, Matsui S, Yoneda T, Takami H, Watanabe K, Osakabe T, Shiraki M, Fukunaga M. Clinical Trials Express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT). J Clin Endocrinol Metab. 2014 Jul;99(7):2599-607. doi: 10.1210/jc.2013-4175. Epub 2014 Mar 19.
PubMed 24646104
Sugimoto T, Matsumoto T, Hosoi T, Miki T, Gorai I, Yoshikawa H, Tanaka Y, Tanaka S, Fukunaga M, Sone T, Nakano T, Ito M, Matsui S, Yoneda T, Takami H, Watanabe K, Osakabe T, Okubo N, Shiraki M, Nakamura T. Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT). Osteoporos Int. 2015 Feb;26(2):765-74. doi: 10.1007/s00198-014-2964-2. Epub 2014 Nov 18.
PubMed 25403903
Okubo N, Matsui S, Matsumoto T, Sugimoto T, Hosoi T, Osakabe T, Watanabe K, Takami H, Shiraki M, Nakamura T. Relationship Between Bone Mineral Density and Risk of Vertebral Fractures with Denosumab Treatment in Japanese Postmenopausal Women and Men with Osteoporosis. Calcif Tissue Int. 2020 Dec;107(6):559-566. doi: 10.1007/s00223-020-00750-y. Epub 2020 Aug 25.
PubMed 32839843

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?

See locations

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A Clinical Study to Collect Real-wordt Data on Safety and Clinical Performance of the VCFix Spinal System for Treatment of Vertebral Compression Fractures of (Suspected) Osteoporotic Origin.
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Active, not recruitingObservational study
The Impact of Osteosarcopenia on Falls, Kinesiophobia, and Quality of Life in Postmenopausal Women
Osteosarcopenia, Sarcopenia
Active, not recruitingPhase 2
TCM Formula vs. HMB in Pre-Frail Elders: Muscle Strength and Bone Status
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Not yet recruitingPhase 4
Romosozumab and Denosumab Combination Therapy for Osteoporosis
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RecruitingObservational study
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All Osteoporosis trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-controlled Phase 3 Study Evaluating Efficacy and Safety of Denosumab in Japanese Osteoporotic Subjects With Prevalent Fragility Vertebral Fracture(s)
ClinicalTrials.gov ID: NCT00680953
Acronym / sponsor ID: DIRECT / AMG162-A-J301
Conditions: Osteoporosis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,262 participants (actual)
Lead sponsor: Daiichi Sankyo Co., Ltd.Industry (pharma, biotech, devices)
Study start: May 2008
Primary completion: Jun 2012 (actual)
Study completion: Jul 2012 (actual)
First posted: 20 May 2008 (estimated)
Results: Posted 26 Feb 2014

Clinical summary

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

Evaluate the efficacy and safety of denosumab in the treatment of involutional (postmenopausal and senile) osteoporotic subjects with prevalent fragility vertebral fracture(s)

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
1	Experimental	Drug: DenosumabDenosumab (subcutaneously - every 6 months) + daily calcium and vitamin D supplements for 24 months, followed by a 12-month period of denosumab (subcutaneously - every 6 months).
2	Placebo comparator	Drug: PlaceboPlacebo (subcutaneously every 6 months) + daily calcium and vitamin D supplements for 24 months, followed by a 12-month period of denosumab (subcutaneously - every 6 months).
3	Active comparator	Drug: Alendronate sodium hydrateAlendronate sodium hydrate oral tablets weekly + daily calcium and vitamin D supplements for 24 months (open label reference arm).

Who may qualify

Ages: 50 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Involutional (postmenopausal and senile) osteoporosis with prevalent fragility vertebral fractures

Key exclusion criteria (1 listed)

Any underlying condition,(other than BMD) that might have resulted in abnormal bone metabolism

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
DenosumabSubcutaneous injection every 6 months for 24 months, followed by a 12-month period of denosumab (subcutaneously - every six months).	Drug	1
PlaceboSubcutaneous injection every 6 months for 24 months, followed by a 12-month period of denosumab (subcutaneously - every six months).	Drug	2
Alendronate sodium hydrateOral tablet once a week for 24 months	Drug	3

Primary outcome

Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo
Time frame: Baseline to 24 months

2 secondary outcomes

The Percentage of Non-vertebral Fractures
Time frame: Baseline to 24 Months
Percentage of Participants With Hip Fractures in Osteoporotic Participants Treated With Denosumab Compared to Treatment With Placebo.
Time frame: Baseline to 24 Months

Results and safety

Results posted to the registry on 26 Feb 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Denosumab	500	414
Placebo	511	416
Alendronate	251	204

Primary outcome: Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo

Time frame: Baseline to 24 months. Mean (95% Confidence Interval). Unit: Vertebral fractures

Measure	Denosumab n = 472	Placebo n = 480	Alendronate n = 242
Value	3.6 (2.2 to 5.8)	10.3 (7.8 to 13.5)	7.2 (4.6 to 11.4)

Denosumab vs Placebo: Hazard Ratio (HR): 0.343 (95% CI 0.194 to 0.606), p = 0.0001, Log Rank

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline to 24 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Denosumab	65 of 475 (13.7%)	475 of 475 (100%)	Not reported
Placebo	68 of 481 (14.1%)	481 of 481 (100%)	Not reported
Alendronate	30 of 242 (12.4%)	242 of 242 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 24646104Nakamura T, Matsumoto T, Sugimoto T, Hosoi T, Miki T, Gorai I, Yoshikawa H, Tanaka Y, Tanaka S, Sone T, Nakano T, Ito M, Matsui S, Yoneda T, Takami H, Watanabe K, Osakabe T, Shiraki M, Fukunaga M. Clinical Trials Express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT). J Clin Endocrinol Metab. 2014 Jul;99(7):2599-607. doi: 10.1210/jc.2013-4175. Epub 2014 Mar 19.
Results publication: PubMed 25403903Sugimoto T, Matsumoto T, Hosoi T, Miki T, Gorai I, Yoshikawa H, Tanaka Y, Tanaka S, Fukunaga M, Sone T, Nakano T, Ito M, Matsui S, Yoneda T, Takami H, Watanabe K, Osakabe T, Okubo N, Shiraki M, Nakamura T. Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT). Osteoporos Int. 2015 Feb;26(2):765-74. doi: 10.1007/s00198-014-2964-2. Epub 2014 Nov 18.
Derived from this study: PubMed 32839843Okubo N, Matsui S, Matsumoto T, Sugimoto T, Hosoi T, Osakabe T, Watanabe K, Takami H, Shiraki M, Nakamura T. Relationship Between Bone Mineral Density and Risk of Vertebral Fractures with Denosumab Treatment in Japanese Postmenopausal Women and Men with Osteoporosis. Calcif Tissue Int. 2020 Dec;107(6):559-566. doi: 10.1007/s00223-020-00750-y. Epub 2020 Aug 25.

Related trials for Osteoporosis

RecruitingObservational study
A Clinical Study to Collect Real-wordt Data on Safety and Clinical Performance of the VCFix Spinal System for Treatment of Vertebral Compression Fractures of (Suspected) Osteoporotic Origin.
Vertebra Compression Fracture
Active, not recruitingObservational study
The Impact of Osteosarcopenia on Falls, Kinesiophobia, and Quality of Life in Postmenopausal Women
Osteosarcopenia, Sarcopenia
Active, not recruitingPhase 2
TCM Formula vs. HMB in Pre-Frail Elders: Muscle Strength and Bone Status
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Not yet recruitingPhase 4
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RecruitingObservational study
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Stroke, Osteoporosis

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.

Daiichi Sankyo study chair

R&D Division, Daiichi Sankyo Co., Ltd.

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Denosumab and Alendronate sodium hydrate in people with Osteoporosis, run by Daiichi Sankyo Co., Ltd. at 4 sites in Japan.

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 1 inclusion and 1 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 12 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

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 26 Feb 2014). 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?

Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo (time frame: Baseline to 24 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 NCT00680953, which also lists 3 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 12 Mar 2015.