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

NCT ID: NCT00112437

Last Updated: 2018-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 399 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-24
• Study Completion Date: 2016-01-20

Brief Summary

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).

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Vitamin D3

Intervention Type: DIETARY_SUPPLEMENT

Vitamin D3, two 2800 IU weekly throughout the study

Calcium Carbonate

Intervention Type: DIETARY_SUPPLEMENT

Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.

Placebo

Intervention Type: DRUG

Placebo to Odanacatib 3 mg, 10 mg, 25 mg, or 50 once weekly for 24 months

Odanacatib 3 mg

Group Type: EXPERIMENTAL

Odanacatib

Intervention Type: DRUG

Odanacatib 3 mg, once weekly for 24 months

Vitamin D3

Intervention Type: DIETARY_SUPPLEMENT

Vitamin D3, two 2800 IU weekly throughout the study

Calcium Carbonate

Intervention Type: DIETARY_SUPPLEMENT

Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.

Odanacatib 10 mg

Group Type: EXPERIMENTAL

Odanacatib

Intervention Type: DRUG

Odanacatib 10 mg, once weekly for 24 months

Vitamin D3

Intervention Type: DIETARY_SUPPLEMENT

Vitamin D3, two 2800 IU weekly throughout the study

Calcium Carbonate

Intervention Type: DIETARY_SUPPLEMENT

Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.

Odanacatib 25 mg

Group Type: EXPERIMENTAL

Odanacatib

Intervention Type: DRUG

Odanacatib 25 mg, once weekly for 24 months

Vitamin D3

Intervention Type: DIETARY_SUPPLEMENT

Vitamin D3, two 2800 IU weekly throughout the study

Calcium Carbonate

Intervention Type: DIETARY_SUPPLEMENT

Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.

Odanacatib 50 mg

Group Type: EXPERIMENTAL

Odanacatib

Intervention Type: DRUG

Odanacatib 50 mg, once weekly for 24 months

Vitamin D3

Intervention Type: DIETARY_SUPPLEMENT

Vitamin D3, two 2800 IU weekly throughout the study

Calcium Carbonate

Intervention Type: DIETARY_SUPPLEMENT

Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.

Interventions

Odanacatib

Odanacatib 3 mg, once weekly for 24 months

Intervention Type: DRUG

Odanacatib

Odanacatib 10 mg, once weekly for 24 months

Intervention Type: DRUG

Odanacatib

Odanacatib 25 mg, once weekly for 24 months

Intervention Type: DRUG

Odanacatib

Odanacatib 50 mg, once weekly for 24 months

Intervention Type: DRUG

Vitamin D3

Vitamin D3, two 2800 IU weekly throughout the study

Intervention Type: DIETARY_SUPPLEMENT

Calcium Carbonate

Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo to Odanacatib 3 mg, 10 mg, 25 mg, or 50 once weekly for 24 months

Intervention Type: DRUG

Other Intervention Names

MK-0822; MK-0822; MK-0822; MK-0822

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• History of prior osteoporotic fracture (unless declined treatment with or was ineligible for osteoporosis therapy)
• 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)

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 19874198 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22777865 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26879200 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20740685 (View on PubMed)

Other Identifiers

2005_023

Identifier Type: -

Identifier Source: secondary_id

0822-004

Identifier Type: -

Identifier Source: org_study_id