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

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).

Study Overview

• Status: Completed
• Conditions: Osteoporosis
• Intervention / Treatment: Dietary supplement: Vitamin D3; Dietary supplement: Calcium Carbonate; Drug: Placebo; Drug: Odanacatib; Drug: Odanacatib; Drug: Odanacatib; Drug: Odanacatib

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.

• Study Type: Interventional
• Enrollment (Actual): 399
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Dietary supplement: Vitamin D3; Vitamin D3, two 2800 IU weekly throughout the study; 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.; Drug: Placebo; Placebo to Odanacatib 3 mg, 10 mg, 25 mg, or 50 once weekly for 24 months
EXPERIMENTAL: Odanacatib 3 mg	Dietary supplement: Vitamin D3; Vitamin D3, two 2800 IU weekly throughout the study; 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.; Drug: Odanacatib; Odanacatib 3 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 10 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 25 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 50 mg, once weekly for 24 months; Other Names: MK-0822
EXPERIMENTAL: Odanacatib 10 mg	Dietary supplement: Vitamin D3; Vitamin D3, two 2800 IU weekly throughout the study; 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.; Drug: Odanacatib; Odanacatib 3 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 10 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 25 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 50 mg, once weekly for 24 months; Other Names: MK-0822
EXPERIMENTAL: Odanacatib 25 mg	Dietary supplement: Vitamin D3; Vitamin D3, two 2800 IU weekly throughout the study; 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.; Drug: Odanacatib; Odanacatib 3 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 10 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 25 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 50 mg, once weekly for 24 months; Other Names: MK-0822
EXPERIMENTAL: Odanacatib 50 mg	Dietary supplement: Vitamin D3; Vitamin D3, two 2800 IU weekly throughout the study; 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.; Drug: Odanacatib; Odanacatib 3 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 10 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 25 mg, once weekly for 24 months; Other Names: MK-0822; Drug: Odanacatib; Odanacatib 50 mg, once weekly for 24 months; Other Names: MK-0822

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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	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.	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.	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.	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.	Years 6-10 (up to 60 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in Total Hip BMD at 12 Months	Percentage change in total hip BMD (relative to baseline) at 12 months	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	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	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	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	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	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.	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	Baseline and 36 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 24, 2005
• Primary Completion (ACTUAL): December 26, 2007
• Study Completion (ACTUAL): January 20, 2016

Study Registration Dates

• First Submitted: June 2, 2005
• First Submitted That Met QC Criteria: June 2, 2005
• First Posted (ESTIMATE): June 3, 2005

Study Record Updates

• Last Update Posted (ACTUAL): January 24, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antacids; Vitamin D; Cholecalciferol; Calcium; Calcium Carbonate
• Other Study ID Numbers: 0822-004; 2005_023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No