OsteoporosisPhase 2NCT00112437

A Study to Examine the Effects of an Experimental Drug on Postmenopausal Osteoporosis (MK-0822-004)

A Phase 2 study testing Odanacatib, Vitamin D3 and Calcium Carbonate in people with Osteoporosis, run by Merck Sharp & Dohme LLC.

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

Who is it for?: Ages 45 to 85 years, women only
Conditions the study is for: Osteoporosis
What is being tested?: Odanacatib, Vitamin D3 and Calcium Carbonate
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 399 participants
Where: No sites listed yet
Study dates: 24 Jun 2005to 20 Jan 2016
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 45 to 85 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Postmenopausal for 5 or more years, defined as no menses for at least 5 years OR at least 5 years status post bilateral oophorectomy
Bone mineral density T-score at the hip or spine of -2.0 or less
Spinal anatomy suitable for dual-energy x-ray absorptiometry (DXA). At the lumbar spine, there is no evidence of vertebral fracture in at least 3 vertebrae in the L1 to L4 region on baseline spine films. (Significant scoliosis, bony trauma, degenerative joint disease, and sequelae of orthopedic procedures that result in anatomy that is unsuitable for accurate bone densitometry must be absent from the lumbar spine.)
At least one hip must be evaluable by DXA (e.g., contain no hardware from orthopedic procedures)
In a state of general health allowing for successful completion of the trial
Agreement to not use any medications to treat osteoporosis during the study

Who cannot join

History of prior osteoporotic fracture (unless declined treatment with or was ineligible for osteoporosis therapy)
Past treatment with osteoporosis medications, steroids, hormone replacement, as well as various other medications that affect bone may be exclusionary. (Different exclusion criteria apply to each bone active drug. For example, any prior use of intravenous (IV) bisphosphonates is not permitted. By contrast, prior use of hormone replacement for several years is permitted if it has not occurred within the past 6 months. Please ask the study doctor for details)
Significant clinical or laboratory abnormalities at the screening visit for the study that, in the opinion of the investigator, could complicate interpretation of the study results or pose additional risk to the patient (for example, patients who are non-ambulatory should be excluded for this reason)

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of MK-0822 (Cathepsin K Inhibitor) in the Treatment of Postmenopausal Women With Osteoporosis

This is a 1-year base study with a 1-year extension to examine the effects of a new experimental medication (odanacatib [MK-0822]) on postmenopausal osteoporosis. This study will enroll approximately 375 postmenopausal women, and randomly assign them to 4 different doses of odanacatib or to placebo. Measurements performed during the study include: bone mineral density scans, spine x-rays, laboratory blood and urine tests, height measurements and optional bone biopsies (at the end of 2 years).

Read the detailed description

Study Extension:

Participants who completed 12 months of the base study and 12 months of the first extension were invited to continue in three additional extensions: MK0-822-004-10, which extended the study to 36 months, MK-0822-004-20 (NCT00112437) which extended the study to 60 months, and MK-0822-004-30 (NCT00112437), which extended the study to 120 months.

In the first extension, participants continued to receive the same treatment they received in the 12-month base study.
In the second extension, participants were re-randomized to odanacatib 50 mg OW or placebo OW for 12 months.
In the third extension, participants who were initially randomized to odanacatib 3 mg or placebo OW in the base study received odanacatib 50 mg weekly in Years 4 and 5; all other participants remained on the same treatment they were during Year 3.
In the fourth extension, all participants received odanacatib weekly in Years 6-10.

Study arms for extensions include only odanacatib 50 mg and placebo for the first two extensions and odanacatib 50 mg only for the third extension.

Extension Studies:

MK-0822-004-10 (NCT00112437) Extension: Participant has participated in and completed 24 months of treatment in the base study

MK-0822-004-20 (NCT00112437) Extension: Participant participated in and completed 36 months of treatment in base and extension studies.

MK-0822-004-30 (NCT00112437) Extension: Participant participated in and completed 60 months of treatment in the base and extension studies.

Conditions: Osteoporosis
Being tested: Odanacatib, Vitamin D3, Calcium Carbonate, Placebo
Medical subject headings: Osteoporosis

What participants receive

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

OdanacatibDrug
Also called MK-0822
Odanacatib 3 mg, once weekly for 24 months
OdanacatibDrug
Also called MK-0822
Odanacatib 10 mg, once weekly for 24 months
OdanacatibDrug
Also called MK-0822
Odanacatib 25 mg, once weekly for 24 months
OdanacatibDrug
Also called MK-0822
Odanacatib 50 mg, once weekly for 24 months
Vitamin D3Dietary supplement
Vitamin D3, two 2800 IU weekly throughout the study
Calcium CarbonateDietary supplement
Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
PlaceboDrug
Placebo to Odanacatib 3 mg, 10 mg, 25 mg, or 50 once weekly for 24 months

Study groups in NCT00112437
Study group	Role	What they receive
Placebo	Placebo comparator	Not described Receives: Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium Carbonate; Drug: Placebo
Odanacatib 3 mg	Experimental	Not described Receives: Drug: Odanacatib; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium Carbonate
Odanacatib 10 mg	Experimental	Not described Receives: Drug: Odanacatib; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium Carbonate
Odanacatib 25 mg	Experimental	Not described Receives: Drug: Odanacatib; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium Carbonate
Odanacatib 50 mg	Experimental	Not described Receives: Drug: Odanacatib; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium Carbonate

What is being measured

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

Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months
Percentage change in lumbar spine BMD (relative to baseline) at 12 Months.
Measured: Baseline and 12 months
Percentage Change From Baseline in Lumbar Spine BMD at 24 Months
Percentage change in lumbar spine BMD (relative to baseline) at 24 Months.
Measured: Baseline and 24 months
Percentage Change From Baseline in Lumbar Spine BMD at 36 Months
Percentage change in lumbar spine BMD (relative to baseline) at 36 months
Measured: Baseline and 36 months
Percentage Change From Baseline in Lumbar Spine BMD at 60 Months
Percentage change from baseline in lumbar spine BMD at 60 months.
Measured: Baseline and Month 60
Percentage Change From Baseline in Lumbar Spine BMD at 120 Months
Percentage change from baseline in lumbar spine BMD at 120 Months.
Measured: Baseline and Month 120
Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Measured: Years 6-10 (up to 60 months, up to 14 days after the last dose of study drug)
Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Measured: Years 6-10 (up to 60 months)

Secondary outcomes (32)

Percentage Change From Baseline in Total Hip BMD at 12 Months
Percentage change in total hip BMD (relative to baseline) at 12 months
Measured: Baseline and 12 months
Percentage Change From Baseline in Femoral Neck BMD at 12 Months
Percentage change in femoral neck BMD (relative to baseline) at 12 months
Measured: Baseline and 12 months
Percentage Change From Baseline in Trochanter BMD at 12 Months
Percentage change in trochanter BMD (relative to baseline) at 12 months
Measured: Baseline and 12 Months
Percentage Change From Baseline in Total Body BMD at 12 Months
Percentage change in total body BMD (relative to baseline) at 12 months
Measured: Baseline and 12 Months
Percentage Change From Baseline in Distal Forearm BMD at 12 Months
Percentage change in distal forearm BMD (relative to baseline) at 12 months
Measured: Baseline and 12 Months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months
Back-transformation (geometric mean) of the Least Squares (LS) Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary N-telopeptides of Type I collagen (u-NTx)) at 12 Months
Measured: Baseline and 12 Months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months
Back-transformation (geometric mean) of the Least Squares (LS) Mean of the log-values Percentage change from baseline in Biochemical Marker of Bone turnover (serum C-telopeptides of Type 1 collagen (s-CTx)) at 12 Months.
Measured: Baseline and 12 Months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values percentage change from baseline in biochemical marker of bone turnover (urinary total deoxypyridinolines (u-DPyr)) (relative to baseline) at 12 Months
Measured: Baseline and 12 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase (s-BSAP)), at 12 Months
Measured: Baseline and 12 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change in Biochemical Marker of Bone turnover (serum N-terminal propeptide of Type 1 collagen (s-P1NP) (relative to baseline) at 12 Months
Measured: Baseline and 12 months
Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months
Percentage change in total hip Bone Mineral Density (relative to baseline) at 24 Months
Measured: Baseline and 24 months
Percentage Change From Baseline in Femoral Neck BMD at 24 Months
Percentage change in femoral neck Bone Mineral Density (relative to baseline) at 24 Months
Measured: Baseline and 24 months
Percentage Change From Baseline in Trochanter BMD at 24 Months
Percentage change from baseline in trochanter BMD (relative to baseline) at 24 Months
Measured: Baseline and 24 months
Percentage Change From Baseline in Total Body BMD at 24 Months
Percentage change in total body BMD (relative to baseline) at 24 Months
Measured: Baseline and 24 months
Percentage Change From Baseline in Distal Forearm BMD at 24 Months
Percentage change in distal forearm BMD (relative to baseline) at 24 Months
Measured: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values percentage change from baseline in biochemical marker of bone turnover (u-NTx) (relative to baseline) at 24 Months
Measured: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum C-telopeptides of Type 1 collagen (s-CTx)) (relative to baseline) at 24 Months
Measured: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary total deoxypyridinolines (u-DPyr)) (relative to baseline) at 24 Months
Measured: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase (s-BSAP)) (relative to baseline) at 24 Months
Measured: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months
Back-transformation (geometric mean) of the least squares mean of the log-values percentage change from baseline in biochemical marker of bone turnover (s-P1NP) (relative to baseline) at 24 months
Measured: Baseline and 24 months
Percentage Change From Baseline in Total Hip BMD at 36 Months
Percentage change in total hip BMD (relative to baseline) at 36 months
Measured: Baseline and 36 months
Percentage Change From Baseline in Femoral Neck BMD at 36 Months
Percentage change in femoral neck BMD (relative to baseline) at 36 Months
Measured: Baseline and 36 months
Percentage Change From Baseline in Trochanter BMD at 36 Months
Percentage change in trochanter BMD (relative to baseline) at 36 months
Measured: Baseline and 36 months
Percentage Change From Baseline in Total Body BMD at 36 Months
Percentage change from baseline in total body BMD (relative to baseline) at 36 Months
Measured: Baseline and 36 months
Percentage Change From Baseline in Distal Forearm BMD at 36 Months
Percentage change in distal forearm BMD (relative to baseline) at 36 Months
Measured: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (u-NTx) at 36 Months
Measured: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (s-CTx) at 36 Months
Measured: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover u-DPyr at 36 Months
Measured: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months
Geometric Mean Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase [s-BSAP]) at 36 Months
Measured: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (serum N-terminal propeptide of Type 1 collagen [s-P1NP]) at 36 months
Measured: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (serum bone tartrate-resistant acid phosphatase isoform 5b [TRAP 5-b]) at 36 Months
Measured: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months
Measured: Baseline and 36 months

Timeline

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

24 Jun 200520 Jan 2016

First posted3 Jun 2005 (estimated)
Study start24 Jun 2005
Primary completion26 Dec 2007
Study completion20 Jan 2016

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 (4)Papers the sponsor has linked to this study.
Other trials for OsteoporosisStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe 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: Double blind
Who is masked: Participant, Investigator
Enrolment: 399 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00112437
Sponsor's protocol ID: 0822-004
Other IDs: 2005_023
Status last verified: Dec 2017
First submitted: 2 Jun 2005
Last updated: 24 Jan 2018
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Bone HG, McClung MR, Roux C, Recker RR, Eisman JA, Verbruggen N, Hustad CM, DaSilva C, Santora AC, Ince BA. Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res. 2010 May;25(5):937-47. doi: 10.1359/jbmr.091035.
PubMed 19874198
Langdahl B, Binkley N, Bone H, Gilchrist N, Resch H, Rodriguez Portales J, Denker A, Lombardi A, Le Bailly De Tilleghem C, Dasilva C, Rosenberg E, Leung A. Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 study. J Bone Miner Res. 2012 Nov;27(11):2251-8. doi: 10.1002/jbmr.1695.
PubMed 22777865
Rizzoli R, Benhamou CL, Halse J, Miller PD, Reid IR, Rodriguez Portales JA, DaSilva C, Kroon R, Verbruggen N, Leung AT, Gurner D. Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study. Osteoporos Int. 2016 Jun;27(6):2099-107. doi: 10.1007/s00198-016-3503-0. Epub 2016 Feb 15.
PubMed 26879200
Eisman JA, Bone HG, Hosking DJ, McClung MR, Reid IR, Rizzoli R, Resch H, Verbruggen N, Hustad CM, DaSilva C, Petrovic R, Santora AC, Ince BA, Lombardi A. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res. 2011 Feb;26(2):242-51. doi: 10.1002/jbmr.212.
PubMed 20740685

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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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
Pre-Frailty, Sarcopenia
Not yet recruitingPhase 4
Romosozumab and Denosumab Combination Therapy for Osteoporosis
Postmenopausal Osteoporosis
RecruitingObservational study
Assessment and Comparison of Osteoporosis Risk Factors After Stroke
Stroke, Osteoporosis

All Osteoporosis trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of MK-0822 (Cathepsin K Inhibitor) in the Treatment of Postmenopausal Women With Osteoporosis
ClinicalTrials.gov ID: NCT00112437
Acronym / sponsor ID: 0822-004
Conditions: Osteoporosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 399 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 24 Jun 2005 (actual)
Primary completion: 26 Dec 2007 (actual)
Study completion: 20 Jan 2016 (actual)
First posted: 3 Jun 2005 (estimated)
Results: Posted 13 May 2010

Clinical summary

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

Detailed description

Study Extension:

In the first extension, participants continued to receive the same treatment they received in the 12-month base study.
In the second extension, participants were re-randomized to odanacatib 50 mg OW or placebo OW for 12 months.
In the third extension, participants who were initially randomized to odanacatib 3 mg or placebo OW in the base study received odanacatib 50 mg weekly in Years 4 and 5; all other participants remained on the same treatment they were during Year 3.
In the fourth extension, all participants received odanacatib weekly in Years 6-10.

Study arms for extensions include only odanacatib 50 mg and placebo for the first two extensions and odanacatib 50 mg only for the third extension.

Extension Studies:

MK-0822-004-10 (NCT00112437) Extension: Participant has participated in and completed 24 months of treatment in the base study

MK-0822-004-20 (NCT00112437) Extension: Participant participated in and completed 36 months of treatment in base and extension studies.

MK-0822-004-30 (NCT00112437) Extension: Participant participated in and completed 60 months of treatment in the base and extension studies.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
Placebo	Placebo comparator	Dietary Supplement: Vitamin D3, Dietary Supplement: Calcium Carbonate, Drug: Placebo
Odanacatib 3 mg	Experimental	Drug: Odanacatib, Dietary Supplement: Vitamin D3, Dietary Supplement: Calcium Carbonate
Odanacatib 10 mg	Experimental	Drug: Odanacatib, Dietary Supplement: Vitamin D3, Dietary Supplement: Calcium Carbonate
Odanacatib 25 mg	Experimental	Drug: Odanacatib, Dietary Supplement: Vitamin D3, Dietary Supplement: Calcium Carbonate
Odanacatib 50 mg	Experimental	Drug: Odanacatib, Dietary Supplement: Vitamin D3, Dietary Supplement: Calcium Carbonate

Who may qualify

Ages: 45 to 85 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Postmenopausal for 5 or more years, defined as no menses for at least 5 years OR at least 5 years status post bilateral oophorectomy
Bone mineral density T-score at the hip or spine of -2.0 or less
Spinal anatomy suitable for dual-energy x-ray absorptiometry (DXA). At the lumbar spine, there is no evidence of vertebral fracture in at least 3 vertebrae in the L1 to L4 region on baseline spine films. (Significant scoliosis, bony trauma, degenerative joint disease, and sequelae of orthopedic procedures that result in anatomy that is unsuitable for accurate bone densitometry must be absent from the lumbar spine.)
At least one hip must be evaluable by DXA (e.g., contain no hardware from orthopedic procedures)
In a state of general health allowing for successful completion of the trial

Key exclusion criteria (3 listed)

History of prior osteoporotic fracture (unless declined treatment with or was ineligible for osteoporosis therapy)
Past treatment with osteoporosis medications, steroids, hormone replacement, as well as various other medications that affect bone may be exclusionary. (Different exclusion criteria apply to each bone active drug. For example, any prior use of intravenous (IV) bisphosphonates is not permitted. By contrast, prior use of hormone replacement for several years is permitted if it has not occurred within the past 6 months. Please ask the study doctor for details)
Significant clinical or laboratory abnormalities at the screening visit for the study that, in the opinion of the investigator, could complicate interpretation of the study results or pose additional risk to the patient (for example, patients who are non-ambulatory should be excluded for this reason)

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
OdanacatibAlso: MK-0822Odanacatib 3 mg, once weekly for 24 months	Drug	Odanacatib 3 mg
OdanacatibAlso: MK-0822Odanacatib 10 mg, once weekly for 24 months	Drug	Odanacatib 10 mg
OdanacatibAlso: MK-0822Odanacatib 25 mg, once weekly for 24 months	Drug	Odanacatib 25 mg
OdanacatibAlso: MK-0822Odanacatib 50 mg, once weekly for 24 months	Drug	Odanacatib 50 mg
Vitamin D3Vitamin D3, two 2800 IU weekly throughout the study	Dietary supplement	Odanacatib 10 mg, Odanacatib 25 mg, Odanacatib 3 mg, Odanacatib 50 mg, Placebo
Calcium CarbonateParticipants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.	Dietary supplement	Odanacatib 10 mg, Odanacatib 25 mg, Odanacatib 3 mg, Odanacatib 50 mg, Placebo
PlaceboPlacebo to Odanacatib 3 mg, 10 mg, 25 mg, or 50 once weekly for 24 months	Drug	Placebo

Primary outcome

Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months
Time frame: Baseline and 12 months
Percentage change in lumbar spine BMD (relative to baseline) at 12 Months.
Percentage Change From Baseline in Lumbar Spine BMD at 24 Months
Time frame: Baseline and 24 months
Percentage change in lumbar spine BMD (relative to baseline) at 24 Months.
Percentage Change From Baseline in Lumbar Spine BMD at 36 Months
Time frame: Baseline and 36 months
Percentage change in lumbar spine BMD (relative to baseline) at 36 months
Percentage Change From Baseline in Lumbar Spine BMD at 60 Months
Time frame: Baseline and Month 60
Percentage change from baseline in lumbar spine BMD at 60 months.
Percentage Change From Baseline in Lumbar Spine BMD at 120 Months
Time frame: Baseline and Month 120
Percentage change from baseline in lumbar spine BMD at 120 Months.
Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months)
Time frame: Years 6-10 (up to 60 months, up to 14 days after the last dose of study drug)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)
Time frame: Years 6-10 (up to 60 months)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.

32 secondary outcomes

Percentage Change From Baseline in Total Hip BMD at 12 Months
Time frame: Baseline and 12 months
Percentage Change From Baseline in Femoral Neck BMD at 12 Months
Time frame: Baseline and 12 months
Percentage Change From Baseline in Trochanter BMD at 12 Months
Time frame: Baseline and 12 Months
Percentage Change From Baseline in Total Body BMD at 12 Months
Time frame: Baseline and 12 Months
Percentage Change From Baseline in Distal Forearm BMD at 12 Months
Time frame: Baseline and 12 Months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months
Time frame: Baseline and 12 Months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months
Time frame: Baseline and 12 Months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months
Time frame: Baseline and 12 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months
Time frame: Baseline and 12 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months
Time frame: Baseline and 12 months
Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Femoral Neck BMD at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Trochanter BMD at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Total Body BMD at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Distal Forearm BMD at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months
Time frame: Baseline and 24 months
Percentage Change From Baseline in Total Hip BMD at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Femoral Neck BMD at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Trochanter BMD at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Total Body BMD at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Distal Forearm BMD at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months
Time frame: Baseline and 36 months
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months
Time frame: Baseline and 36 months

Results and safety

Results posted to the registry on 13 May 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-Base	83	68
Odanacatib 3 Mg-Base	82	64
Odanacatib 10 Mg-Base	77	65
Odanacatib 25 Mg-Base	79	71
Odanacatib 50 Mg-Base	78	66
Placebo-Ext 1	0	0
Odanacatib 3 Mg-Ext 1	0	0
Odanacatib 10 Mg-Ext 1	0	0
Odanacatib 25 Mg-Ext 1	0	0
Odanacatib 50 Mg-Ext 1	0	0
Placebo / Placebo-Ext 2	0	0
Placebo / Odanacatib 50 Mg-Ext 2	0	0
Odanacatib 3 mg / Placebo-Ext 2	0	0
Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2	0	0
Odanacatib 10 mg / Placebo-Ext 2	0	0
Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2	0	0
Odanacatib 25 mg / Placebo-Ext 2	0	0
Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2	0	0
Odanacatib 50 mg / Placebo-Ext 2	0	0
Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2	0	0
Placebo Once Weekly-Ext 3	0	0
Odanacatib 50 mg Once Weekly-Ext 3	0	0
Group A: Odanacatib 50 mg Once Weekly-Ext 4	0	0
Group B: Odanacatib 50 mg Once Weekly-Ext 4	0	0
Group C: Odanacatib 50 mg Once Weekly-Ext 4	0	0
Group D: Odanacatib 50 mg Once Weekly-Ext 4	0	0

Primary outcome: Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months

Time frame: Baseline and 12 months. Least squares mean (95% Confidence Interval). Unit: Percentage change

Measure	Placebo-Base n = 81	Odanacatib 3 Mg-Base n = 79	Odanacatib 10 Mg-Base n = 77	Odanacatib 25 Mg-Base n = 78	Odanacatib 50 Mg-Base n = 77
Value	-0.13 (-0.80 to 0.54)	-0.62 (-1.30 to 0.05)	1.50 (0.82 to 2.19)	2.65 (1.97 to 3.33)	3.37 (2.68 to 4.05)

Placebo-Base vs Odanacatib 50 Mg-Base: Difference in Least Squares Means: 3.50 (95% CI 2.54 to 4.45), p <=0.001, ANCOVA
Placebo-Base vs Odanacatib 25 Mg-Base: Difference in Least Squares Means: 2.78 (95% CI 1.82 to 3.73), p <=0.001, ANCOVA
Placebo-Base vs Odanacatib 10 Mg-Base: Difference in Least Squares Means: 1.63 (95% CI 0.68 to 2.59), p = 0.003, ANCOVA

Population analysed: Analysis at Month 12 used Full-Analysis-Set Population of participants who took at least one dose of study medication and had necessary follow-up information, in their randomization treatment group, with last observation data carried forward. Seven patients had a baseline value, but no value at Month 12 for lumbar spine Bone Mineral Density.

Primary outcome: Percentage Change From Baseline in Lumbar Spine BMD at 24 Months

Time frame: Baseline and 24 months. Least squares mean (95% Confidence Interval). Unit: Percentage Change

Measure	Placebo-Ext 1 n = 62	Odanacatib 3 Mg-Ext 1 n = 58	Odanacatib 10 Mg-Ext 1 n = 60	Odanacatib 25 Mg-Ext 1 n = 65	Odanacatib 50 Mg-Ext 1 n = 58
Value	-0.19 (-1.13 to 0.75)	-1.03 (-2.00 to -0.07)	3.20 (2.25 to 4.15)	4.26 (3.35 to 5.18)	5.48 (4.52 to 6.44)

Placebo-Ext 1 vs Odanacatib 50 Mg-Ext 1: Difference in Least Squares Means: 5.67 (95% CI 4.32 to 7.02), p <=0.001, ANCOVA
Placebo-Ext 1 vs Odanacatib 25 Mg-Ext 1: Difference in Least Squares Means: 4.45 (95% CI 3.15 to 5.76), p <=0.001, ANCOVA
Placebo-Ext 1 vs Odanacatib 10 Mg-Ext 1: Difference in Least Squares Means: 3.39 (95% CI 2.06 to 4.73), p <=0.001, ANCOVA

Population analysed: Analysis on lumbar spine BMD (g/cm2) at Month 24 used the Full-Analysis-Set Population with Last Observation Carried Forward from Month 18 to 24. No data were carried forward from the core to the extension period. Only patients who took at least one dose of extension medication were included. 17 patients were excluded from FAS.

Primary outcome: Percentage Change From Baseline in Lumbar Spine BMD at 36 Months

Time frame: Baseline and 36 months. Least squares mean (95% Confidence Interval). Unit: Percent Change

Measure	Placebo / Placebo-Ext 2 n = 14	Placebo / Odanacatib 50 Mg-Ext 2 n = 16	Odanacatib 3 mg / Placebo-Ext 2 n = 17	Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 n = 13	Odanacatib 10 mg / Placebo-Ext 2 n = 12	Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 n = 10	Odanacatib 25 mg / Placebo-Ext 2 n = 12	Odanacatib 25 mg / 50 Mg-Ext 2 n = 18	Odanacatib 50 mg / Placebo-Ext 2 n = 15	Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 n = 17
Value	0.42 (-1.89 to 2.73)	2.95 (0.79 to 5.11)	-1.57 (-3.67 to 0.54)	4.41 (2.01 to 6.82)	2.03 (-0.47 to 4.53)	6.11 (3.37 to 8.85)	0.32 (-2.18 to 2.82)	7.45 (5.41 to 9.48)	1.39 (-0.84 to 3.63)	7.85 (5.74 to 9.95)

Odanacatib 50 mg / Placebo-Ext 2 vs Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2: Difference in Least Square Means: 6.45 (95% CI 3.38 to 9.53)

Population analysed: This analysis was performed at Month 36 using the Per-protocol approach which includes patients who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from month 30 to 36.

Primary outcome: Percentage Change From Baseline in Lumbar Spine BMD at 60 Months

Time frame: Baseline and Month 60. Mean (95% Confidence Interval). Unit: Percentage change

Measure	Placebo Once Weekly n = 14	Odanacatib 50 mg Once Weekly n = 13
Value	-0.41 (-3.1 to 2.28)	11.88 (7.23 to 16.54)

Population analysed: All participants who took at least one dose of base study medication and at least one dose of extension medication. Missing values were imputed using last observation-carried-forward principle.

32 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events data were collected up to 120 months (from start of study medication, up to 14 days after the last dose).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Years 1-2 Placebo/Placebo-Ext 1	8 of 83 (9.6%)	68 of 83 (81.9%)	Not reported
Years 1-2 Odanacatib 3 mg/Odanacatib 3 Mg-Ext 1	12 of 82 (14.6%)	66 of 82 (80.5%)	Not reported
Years 1-2 Odanacatib 10 mg/Odanacatib 10 Mg-Ext 1	10 of 77 (13%)	67 of 77 (87%)	Not reported
Years 1-2 Odanacatib 25 mg/Odanacatib 25 Mg-Ext 1	9 of 79 (11.4%)	67 of 79 (84.8%)	Not reported
Years 1-2 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 1	14 of 78 (17.9%)	66 of 78 (84.6%)	Not reported
Year 3 Placebo/Placebo-Ext 2	2 of 19 (10.5%)	17 of 19 (89.5%)	Not reported
Year 3 Placebo/Odanacatib 50 Mg-Ext 2	2 of 22 (9.1%)	13 of 22 (59.1%)	Not reported
Year 3 Odanacatib 3 mg/Placebo-Ext 2	3 of 18 (16.7%)	16 of 18 (88.9%)	Not reported
Year 3 Odanacatib 3 mg/Odanacatib 50 Mg-Ext 2	2 of 17 (11.8%)	14 of 17 (82.4%)	Not reported
Year 3 Odanacatib 10 mg/Placebo-Ext 2	1 of 18 (5.6%)	13 of 18 (72.2%)	Not reported
Year 3 Odanacatib 10 mg/Odanacatib 50 Mg-Ext 2	1 of 17 (5.9%)	15 of 17 (88.2%)	Not reported
Year 3 Odanacatib 25 mg/Placebo-Ext 2	2 of 19 (10.5%)	15 of 19 (78.9%)	Not reported
Year 3 Odanacatib 25 mg/Odanacatib 50 Mg-Ext 2	3 of 21 (14.3%)	17 of 21 (81%)	Not reported
Year 3 Odanacatib 50 mg/Placebo-Ext 2	2 of 18 (11.1%)	14 of 18 (77.8%)	Not reported
Year 3 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 2	1 of 20 (5%)	15 of 20 (75%)	Not reported
Years 4-5 Combined Group A.1: Odanacatib 50 mg	16 of 73 (21.9%)	64 of 73 (87.7%)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19874198Bone HG, McClung MR, Roux C, Recker RR, Eisman JA, Verbruggen N, Hustad CM, DaSilva C, Santora AC, Ince BA. Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res. 2010 May;25(5):937-47. doi: 10.1359/jbmr.091035.
Results publication: PubMed 22777865Langdahl B, Binkley N, Bone H, Gilchrist N, Resch H, Rodriguez Portales J, Denker A, Lombardi A, Le Bailly De Tilleghem C, Dasilva C, Rosenberg E, Leung A. Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 study. J Bone Miner Res. 2012 Nov;27(11):2251-8. doi: 10.1002/jbmr.1695.
Results publication: PubMed 26879200Rizzoli R, Benhamou CL, Halse J, Miller PD, Reid IR, Rodriguez Portales JA, DaSilva C, Kroon R, Verbruggen N, Leung AT, Gurner D. Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study. Osteoporos Int. 2016 Jun;27(6):2099-107. doi: 10.1007/s00198-016-3503-0. Epub 2016 Feb 15.
Derived from this study: PubMed 20740685Eisman JA, Bone HG, Hosking DJ, McClung MR, Reid IR, Rizzoli R, Resch H, Verbruggen N, Hustad CM, DaSilva C, Petrovic R, Santora AC, Ince BA, Lombardi A. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res. 2011 Feb;26(2):242-51. doi: 10.1002/jbmr.212.

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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.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Odanacatib, Vitamin D3 and Calcium Carbonate in people with Osteoporosis, run by Merck Sharp & Dohme LLC.

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 3 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 24 Jan 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 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 13 May 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?

Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months (time frame: Baseline and 12 months). The study lists 7 primary outcomes in all. 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 NCT00112437, which also lists 4 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 24 Jan 2018.