Clinical trial NCT00112437: A Study to Examine the Effects of an Experimental Drug on Postmenopausal Osteoporosis (MK-0822-004)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoporosis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2005-06-03
Enrollment: 399
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)
* 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)

Primary outcomes:
measure: Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months
timeFrame: Baseline and 12 months
measure: Percentage Change From Baseline in Lumbar Spine BMD at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Lumbar Spine BMD at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Lumbar Spine BMD at 60 Months
timeFrame: Baseline and Month 60
measure: Percentage Change From Baseline in Lumbar Spine BMD at 120 Months
timeFrame: Baseline and Month 120
measure: Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months)
timeFrame: Years 6-10 (up to 60 months, up to 14 days after the last dose of study drug)
measure: Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)
timeFrame: Years 6-10 (up to 60 months)
Secondary outcomes:
measure: Percentage Change From Baseline in Total Hip BMD at 12 Months
timeFrame: Baseline and 12 months
measure: Percentage Change From Baseline in Femoral Neck BMD at 12 Months
timeFrame: Baseline and 12 months
measure: Percentage Change From Baseline in Trochanter BMD at 12 Months
timeFrame: Baseline and 12 Months
measure: Percentage Change From Baseline in Total Body BMD at 12 Months
timeFrame: Baseline and 12 Months
measure: Percentage Change From Baseline in Distal Forearm BMD at 12 Months
timeFrame: Baseline and 12 Months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months
timeFrame: Baseline and 12 Months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months
timeFrame: Baseline and 12 Months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months
timeFrame: Baseline and 12 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months
timeFrame: Baseline and 12 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months
timeFrame: Baseline and 12 months
measure: Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Femoral Neck BMD at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Trochanter BMD at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Total Body BMD at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Distal Forearm BMD at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months
timeFrame: Baseline and 24 months
measure: Percentage Change From Baseline in Total Hip BMD at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Femoral Neck BMD at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Trochanter BMD at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Total Body BMD at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Distal Forearm BMD at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months
timeFrame: Baseline and 36 months
measure: Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months
timeFrame: Baseline and 36 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.