A Study to Evaluate the Safety, Tolerability, and Efficacy of Odanacatib (MK-0822) in Postmenopausal Women Previously Treated With a Bisphosphonate (MK-0822-042)

Study Overview
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Brief Summary
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The study will evaluate the both the efficacy of odanacatib on Bone Mineral Density (BMD) and the safety of odanacatib for postmenopausal osteoporosis in patients previously treated with alendronate. The primary hypothesis of the trial is that treatment with odanacatib 50 mg once weekly will increase bone mineral density at the femoral neck compared to placebo at the end of 24 months.

Official Title
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A Phase IIa Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Effects of Odanacatib (MK-0822) on Bone Mineral Density (BMD) and Overall Safety in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With Alendronate

Conditions
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Osteoporosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has been postmenopausal for at least 5 years Has taken or is taking alendronate Agrees not to use medications for osteoporosis other than what is provided by the study Exclusion Criteria: Has a history or evidence of hip fracture Has a history of cancer within 5 years of screening, except certain skin or cervical cancers. Has active parathyroid disease Has a history of thyroid disease not adequately controlled by medication Is taking anti-seizure medication and has abnormal calcium metabolism Has received any bisphosphonate other than alendronate for 20% of the last 3 years, or within 3 months of screening

Ages Eligible for Study
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Minimum Age: 60 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 |
| --- | --- |
| Experimental: Odanacatib 50 mg<br>Odanacatib 50 mg tablets once weekly for 24 months. Vitamin D3 (dietary supplement), two 2800 IU tablets, taken once weekly for 24 months. Participants received calcium carbonate supplements as needed to ensure a daily calcium intake of 1200 mg. | Drug: Odanacatib<br>* Odanacatib 50 mg tablets once weekly for 24 months<br>Dietary Supplement: Vitamin D3<br>* Vitamin D3, two 2800 IU tablets, taken once weekly for 24 months<br>Dietary Supplement: Calcium<br>* Participants will receive calcium carbonate supplements as needed to ensure a daily calcium intake of 1200 mg.<br>|
| Placebo Comparator: Placebo<br>Placebo to odanacatib 50 mg tablets once weekly for 24 months. Vitamin D3 (dietary supplement), two 2800 IU tablets, taken once weekly for 24 months. Participants received calcium carbonate supplements as needed to ensure a daily calcium intake of 1200 mg. | Drug: Placebo<br>* Placebo to odanacatib 50 mg tablets once weekly for 24 months<br>Dietary Supplement: Vitamin D3<br>* Vitamin D3, two 2800 IU tablets, taken once weekly for 24 months<br>Dietary Supplement: Calcium<br>* Participants will receive calcium carbonate supplements as needed to ensure a daily calcium intake of 1200 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Month 24 | BMD at the femoral neck was assessed by dual-energy X-ray absorptiometry (DXA) at baseline and Month 24. | Baseline and Month 24 | 
| Percentage of Participants Experiencing One or More Adverse Events (AEs) | An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. | Up to 25 months | 
| Percentage of Participants Discontinuing Study Drug Due to an AE | An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Femoral Neck BMD at Month 12 | BMD at the femoral neck was assessed by DXA at baseline and Month 12. | Baseline and 12 Months | 
| Percent Change From Baseline in Trochanter BMD at Month 24 | BMD at the trochanter was assessed by DXA at baseline and Month 24. | Baseline and 24 Months | 
| Percent Change From Baseline in Trochanter BMD at Month 12 | BMD at the trochanter was assessed by DXA at baseline and Month 12. | Baseline and 12 Months | 
| Percent Change From Baseline in Total Hip BMD at Month 24 | BMD at the total hip was assessed by DXA at baseline and Month 24. | Baseline and 24 Months | 
| Percent Change From Baseline in Total Hip BMD at Month 12 | BMD at the total hip was assessed by DXA at baseline and Month 12. | Baseline and 12 Months | 
| Percent Change From Baseline in Lumbar Spine BMD at Month 24 | BMD at the lumbar spine was assessed by DXA at baseline and Month 24. | Baseline and 24 Months | 
| Percent Change From Baseline in Lumbar Spine BMD at Month 12 | BMD at the lumbar spine was assessed by DXA at baseline and Month 12. | Baseline and 12 Months | 
| Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 24 | BMD at the 1/3 distal forearm was assessed by DXA at baseline and Month 24. | Baseline and 24 Months | 
| Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 12 | BMD at the 1/3 distal forearm was assessed by DXA at baseline and Month 12. | Baseline and 12 Months | 
| Percent Change From Baseline in Log-Transformed Serum C-Telopeptides of Type I Collagen (s-CTx) at Month 24 | s-CTx is a biochemical marker of bone resorption. | Baseline and Month 24 | 
| Percent Change From Baseline in Log-Transformed s-CTx at Month 12 | s-CTx is a biochemical marker of bone resorption. | Baseline and Month 12 | 
| Percent Change From Baseline in Log-Transformed Urine N-Telopeptides/Creatinine Ratio at Month 24 | N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio (u-NTx/Cr) is a biochemical marker of bone resorption. | Baseline and Month 24 | 
| Percent Change From Baseline in Log-Transformed u-NTx/Cr at Month 12 | u-NTx/Cr is a biochemical marker of bone resorption. | Baseline and Month 12 | 
| Percent Change From Baseline in Log-Transformed Serum Bone-Specific Alkaline Phosphatase at Month 24 | Bone-Specific Alkaline Phosphatase (BSAP) is a biochemical marker of bone formation. | Baseline and Month 24 | 
| Percent Change From Baseline in Log-Transformed Serum BSAP at Month 12 | BSAP is a biochemical marker of bone formation. | Baseline and Month 12 | 
| Percent Change From Baseline in Log-Transformed Serum N-Terminal Propeptide of Type I Collagen at Month 24 | Serum N-terminal propeptide of Type I collagen (s-P1NP) is a biochemical marker of bone formation. | Baseline and Month 24 | 
| Percent Change From Baseline in Log-Transformed Serum N-terminal Propeptide of Type I Collagen at Month 12 | s-P1NP is a biochemical marker of bone formation. | Baseline and Month 12 | 
| Percent Change From Baseline in Log-Transformed Serum Calcium at Month 24 | Serum calcium is an index of calcium homeostasis. | Baseline and Month 24 | 
| Percent Change From Baseline in Log-Transformed Serum Phosphate at Month 24 | Serum phosphate is an index of mineral homeostasis. | Baseline and Month 24 | 
| Percent Change From Baseline in Log-Transformed Serum Parathyroid Hormone at Month 24 | Serum parathyroid hormone (SPH) regulates calcium, phosphorus, and vitamin D levels in the blood. | Baseline and Month 24 | 
| Percent Change From Baseline in Log-Transformed Serum 1,25 Dihydroxyvitamin D at Month 24 | 1,25 dihydroxyvitamin D [1,25(OH)2 D] is the active vitamin D metabolite and stimulates calcium absorption in the intestine. | Baseline and Month 24 | 
| Percent Change From Baseline in Log-Transformed Serum 25-Hydroxyvitamin D at Month 24 | The 25-hydroxy vitamin D [25(OH)D] test is the most accurate way to measure vitamin D. In the kidney, 25-hydroxy vitamin D is converted into 1,25 di-hydroxyvitamin D, the active vitamin D metabolite. | Baseline and Month 24 |