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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Odanacatib
* Drug: Odanacatib
* Drug: Odanacatib
* Drug: Odanacatib
* Dietary Supplement: Vitamin D3
* Dietary Supplement: Calcium Carbonate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Dietary Supplement: Vitamin D3<br>* Vitamin D3, two 2800 IU weekly throughout the study<br>Dietary Supplement: Calcium Carbonate<br>* Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.<br>Drug: Placebo<br>* Placebo to Odanacatib 3 mg, 10 mg, 25 mg, or 50 once weekly for 24 months<br>|
| Experimental: Odanacatib 3 mg<br> | Drug: Odanacatib<br>* Odanacatib 3 mg, once weekly for 24 months<br>* Other names: MK-0822;Dietary Supplement: Vitamin D3<br>* Vitamin D3, two 2800 IU weekly throughout the study<br>Dietary Supplement: Calcium Carbonate<br>* Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.<br>|
| Experimental: Odanacatib 10 mg<br> | Drug: Odanacatib<br>* Odanacatib 10 mg, once weekly for 24 months<br>* Other names: MK-0822;Dietary Supplement: Vitamin D3<br>* Vitamin D3, two 2800 IU weekly throughout the study<br>Dietary Supplement: Calcium Carbonate<br>* Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.<br>|
| Experimental: Odanacatib 25 mg<br> | Drug: Odanacatib<br>* Odanacatib 25 mg, once weekly for 24 months<br>* Other names: MK-0822;Dietary Supplement: Vitamin D3<br>* Vitamin D3, two 2800 IU weekly throughout the study<br>Dietary Supplement: Calcium Carbonate<br>* Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.<br>|
| Experimental: Odanacatib 50 mg<br> | Drug: Odanacatib<br>* Odanacatib 50 mg, once weekly for 24 months<br>* Other names: MK-0822;Dietary Supplement: Vitamin D3<br>* Vitamin D3, two 2800 IU weekly throughout the study<br>Dietary Supplement: Calcium Carbonate<br>* Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.<br>|

What is the study measuring?
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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 |