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 Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition:	Osteoporosis
Interventions:	Drug: Odanacatib; Drug: Placebo; Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled and treated in 40 study centers located in the United States, Europe, South Africa, and Asia-Pacific.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Women ≥ 60 years of age who had been on, or were on, an alendronate therapy for postmenopausal osteoporosis were eligible to participate in this trial.

Reporting Groups

	Description
Odanacatib 50 mg	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 approximately 1200 mg.
Placebo	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 approximately 1200 mg.

Participant Flow:   Overall Study

	Odanacatib 50 mg	Placebo
STARTED	124	122
Treated	122	121
COMPLETED	86	99
NOT COMPLETED	38	23
Adverse Event	12	4
Excessive bone loss	6	3
Lost to Follow-up	2	1
Physician Decision	2	1
Protocol Violation	3	1
Withdrawal by Subject	13	13

  Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The baseline characteristics are displayed for the All-Participants-As-Treated Population.

Reporting Groups

	Description
Odanacatib 50 mg	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 approximately 1200 mg.
Placebo	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 approximately 1200 mg.
Total	Total of all reporting groups

Baseline Measures

	Odanacatib 50 mg	Placebo	Total
Overall Participants Analyzed; [Units: Participants]	122	121	243
Age; [Units: Years]; Mean (Standard Deviation)	71.5 (6.7)	71.1 (6.8)	71.3 (6.8)
Sex: Female, Male; [Units: Participants]; Count of Participants
Female	122 100.0%	121 100.0%	243 100.0%
Male	0 0.0%	0 0.0%	0 0.0%
Baseline DEXA Areal Bone Mineral Density T-score [1]; [Units: T-score]; Mean (Standard Deviation)
Femoral Neck BMD T-score (122, 121, 243)	-2.35 (0.52)	-2.38 (0.48)	-2.36 (0.50)
Hip Trochanter BMD T-score (122, 121, 243)	-1.91 (0.70)	-2.10 (0.79)	-2.00 (0.75)
Total Hip BMD T-score (122, 121, 243)	-1.91 (0.62)	-2.05 (0.68)	-1.98 (0.65)
Lumbar Spine BMD T-score (113, 116, 229)	-2.34 (1.10)	-2.49 (1.14)	-2.41 (1.12)
1/3 Distal Forearm BMD T-score (114, 113, 227)	-2.62 (1.26)	-2.69 (1.10)	-2.65 (1.18)
[1] Dual-energy X-ray absorptiometry (DEXA), Bone Mineral Density (BMD), T-score. T-Score is the difference between the BMD value and the average bone mass for sex-matched, healthy young adults; the difference being expressed in number of standard deviations; T-score based upon the normative database in use by the manufactures. A T-score of -1.0 or above is considered normal. More negative numbers are more indicative of osteoporosis.
Baseline Biochemical Markers of Bone Resorption and Bone Formation; [Units: ng/mL]; Mean (Standard Deviation)
C-telopeptides of Type 1 collage (116, 117,233)	0.19 (0.22)	0.18 (0.14)	0.19 (0.19)
Serum bone specific alk. phosphatase (115,117,232)	9.28 (4.63)	9.41 (4.16)	9.35 (4.39)
Serum N-propeptide, T1 collagen (115, 117, 232)	29.48 (28.18)	27.79 (21.58)	28.63 (25.03)
Urine N-Telopeptides/Creatinine Ratio [1]; [Units: Nmol/mmol]; Mean (Standard Deviation)	26.00 (23.76)	26.35 (18.08)	26.17 (21.08)
[1] u-NTx/Cr (nmol/mmol), Odanacatib 50 mg N=115, Placebo N=114, Total N=229

  Outcome Measures

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1. Primary:

Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at Month 24 [ Time Frame: Baseline and Month 24 ]

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2. Primary:

Percentage of Participants Experiencing One or More Adverse Events (AEs) [ Time Frame: Up to 25 months ]

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3. Primary:

Percentage of Participants Discontinuing Study Drug Due to an AE [ Time Frame: Up to 24 months ]

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4. Secondary:

Percent Change From Baseline in Femoral Neck BMD at Month 12 [ Time Frame: Baseline and 12 Months ]

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5. Secondary:

Percent Change From Baseline in Trochanter BMD at Month 24 [ Time Frame: Baseline and 24 Months ]

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6. Secondary:

Percent Change From Baseline in Trochanter BMD at Month 12 [ Time Frame: Baseline and 12 Months ]

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7. Secondary:

Percent Change From Baseline in Total Hip BMD at Month 24 [ Time Frame: Baseline and 24 Months ]

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8. Secondary:

Percent Change From Baseline in Total Hip BMD at Month 12 [ Time Frame: Baseline and 12 Months ]

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9. Secondary:

Percent Change From Baseline in Lumbar Spine BMD at Month 24 [ Time Frame: Baseline and 24 Months ]

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10. Secondary:

Percent Change From Baseline in Lumbar Spine BMD at Month 12 [ Time Frame: Baseline and 12 Months ]

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11. Secondary:

Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 24 [ Time Frame: Baseline and 24 Months ]

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12. Secondary:

Percent Change From Baseline in 1/3 Distal Forearm BMD at Month 12 [ Time Frame: Baseline and 12 Months ]

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13. Secondary:

Percent Change From Baseline in Log-Transformed Serum C-Telopeptides of Type I Collagen (s-CTx) at Month 24 [ Time Frame: Baseline and Month 24 ]

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14. Secondary:

Percent Change From Baseline in Log-Transformed s-CTx at Month 12 [ Time Frame: Baseline and Month 12 ]

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15. Secondary:

Percent Change From Baseline in Log-Transformed Urine N-Telopeptides/Creatinine Ratio at Month 24 [ Time Frame: Baseline and Month 24 ]

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16. Secondary:

Percent Change From Baseline in Log-Transformed u-NTx/Cr at Month 12 [ Time Frame: Baseline and Month 12 ]

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17. Secondary:

Percent Change From Baseline in Log-Transformed Serum Bone-Specific Alkaline Phosphatase at Month 24 [ Time Frame: Baseline and Month 24 ]

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18. Secondary:

Percent Change From Baseline in Log-Transformed Serum BSAP at Month 12 [ Time Frame: Baseline and Month 12 ]

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19. Secondary:

Percent Change From Baseline in Log-Transformed Serum N-Terminal Propeptide of Type I Collagen at Month 24 [ Time Frame: Baseline and Month 24 ]

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20. Secondary:

Percent Change From Baseline in Log-Transformed Serum N-terminal Propeptide of Type I Collagen at Month 12 [ Time Frame: Baseline and Month 12 ]

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21. Secondary:

Percent Change From Baseline in Log-Transformed Serum Calcium at Month 24 [ Time Frame: Baseline and Month 24 ]

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22. Secondary:

Percent Change From Baseline in Log-Transformed Serum Phosphate at Month 24 [ Time Frame: Baseline and Month 24 ]

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23. Secondary:

Percent Change From Baseline in Log-Transformed Serum Parathyroid Hormone at Month 24 [ Time Frame: Baseline and Month 24 ]

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24. Secondary:

Percent Change From Baseline in Log-Transformed Serum 1,25 Dihydroxyvitamin D at Month 24 [ Time Frame: Baseline and Month 24 ]

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25. Secondary:

Percent Change From Baseline in Log-Transformed Serum 25-Hydroxyvitamin D at Month 24 [ Time Frame: Baseline and Month 24 ]

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  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Certain Agreements:  

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.

Results Point of Contact:  

Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Bonnick S, De Villiers T, Odio A, Palacios S, Chapurlat R, DaSilva C, Scott BB, Le Bailly De Tilleghem C, Leung AT, Gurner D. Effects of odanacatib on BMD and safety in the treatment of osteoporosis in postmenopausal women previously treated with alendronate: a randomized placebo-controlled trial. J Clin Endocrinol Metab. 2013 Dec;98(12):4727-35. doi: 10.1210/jc.2013-2020. Epub 2013 Sep 24.

Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT00885170 History of Changes
Other Study ID Numbers:	0822-042; 2009_578 ( Other Identifier: Merck Registration Number ); CTRI/2009/091/000218 ( Registry Identifier: CTRI ); 2008-008257-30 ( EudraCT Number )
First Submitted:	April 20, 2009
First Posted:	April 21, 2009
Results First Submitted:	January 3, 2017
Results First Posted:	April 18, 2017
Last Update Posted:	April 18, 2017