Clinical Trial Results:
A Phase III Randomized, Placebo-Controlled Clinical Trial to Assess the Safety and Efficacy of Odanacatib (MK-0822) to Reduce the Risk of Fracture in Osteoporotic Postmenopausal Women Treated With Vitamin D and Calcium (MK-0822-018)
Summary
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EudraCT number |
2007-002693-66 |
Trial protocol |
LT DK CZ PL GB DE FR BE LV EE IT ES BG |
Global end of trial date |
01 Feb 2017
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Results information
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Results version number |
v1 |
This version publication date |
03 Mar 2018
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First version publication date |
03 Mar 2018
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
0822-018
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00529373 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Secondary Id: 2007_610, Registry Identifier: 132238 | ||
Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Feb 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Feb 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The purpose of the event-driven base study is to determine the safety and efficacy, especially fracture risk reduction, of odanacatib in postmenopausal women diagnosed with osteoporosis. In a placebo-controlled extension of the base study, participants continued to receive the same blinded study medication for a total of up to 5 years of blinded study medication combined between the base study and the extension. After participants received 5 years of blinded study medication, they received open-label odanacatib through the end of the first extension. Participants were then invited to enroll in a second extension study in which they received open-label odanacatib for an additional 5 years. Two imaging substudies (PN032-Base/Extension and PN035) were conducted for participants in the MK-0822-018 Study. Additional safety information was collected for participants who discontinued from the base study or the blinded first extension in an observational follow-up study, MK-0822-083.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
Participants received standard-of-care therapy with Vitamin D3 (oral tablet; 5600 IU orally once weekly [OW]) and calcium carbonate (oral tablet; total daily calcium intake approximately 1200 mg but not to exceed 1600 mg) dietary supplements. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Sep 2007
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy, Regulatory reason | ||
Long term follow-up duration |
10 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 280
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Country: Number of subjects enrolled |
Australia: 3
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Country: Number of subjects enrolled |
Belgium: 37
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Country: Number of subjects enrolled |
Brazil: 1611
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Country: Number of subjects enrolled |
Bulgaria: 220
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Country: Number of subjects enrolled |
Chile: 62
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Country: Number of subjects enrolled |
China: 610
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Country: Number of subjects enrolled |
Colombia: 1999
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Country: Number of subjects enrolled |
Croatia: 33
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Country: Number of subjects enrolled |
Czech Republic: 317
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Country: Number of subjects enrolled |
Denmark: 1048
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Country: Number of subjects enrolled |
Dominican Republic: 144
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Country: Number of subjects enrolled |
Estonia: 170
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Country: Number of subjects enrolled |
France: 42
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Country: Number of subjects enrolled |
Germany: 27
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Country: Number of subjects enrolled |
Guatemala: 293
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Country: Number of subjects enrolled |
Hong Kong: 211
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Country: Number of subjects enrolled |
India: 981
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Country: Number of subjects enrolled |
Italy: 79
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Country: Number of subjects enrolled |
Japan: 454
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Country: Number of subjects enrolled |
Korea, Republic of: 194
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Country: Number of subjects enrolled |
Latvia: 53
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Country: Number of subjects enrolled |
Lebanon: 19
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Country: Number of subjects enrolled |
Lithuania: 178
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Country: Number of subjects enrolled |
Mexico: 421
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Country: Number of subjects enrolled |
New Zealand: 86
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Country: Number of subjects enrolled |
Norway: 289
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Country: Number of subjects enrolled |
Peru: 603
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Country: Number of subjects enrolled |
Philippines: 116
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Country: Number of subjects enrolled |
Poland: 1171
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Country: Number of subjects enrolled |
Romania: 129
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Country: Number of subjects enrolled |
Russian Federation: 793
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Country: Number of subjects enrolled |
Serbia: 60
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Country: Number of subjects enrolled |
South Africa: 1129
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Country: Number of subjects enrolled |
Spain: 61
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Country: Number of subjects enrolled |
Switzerland: 27
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Country: Number of subjects enrolled |
Taiwan: 64
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Country: Number of subjects enrolled |
Ukraine: 84
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Country: Number of subjects enrolled |
United Kingdom: 1711
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Country: Number of subjects enrolled |
United States: 262
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Worldwide total number of subjects |
16071
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EEA total number of subjects |
5565
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
12
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From 65 to 84 years |
15650
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85 years and over |
409
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Additional screening criteria applied. | |||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Base Study
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||||||||
Roles blinded |
Investigator, Subject | |||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Odanacatib 50 mg OW | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Odanacatib
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Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||
Other name |
MK-0822
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Arm title
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Placebo | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo for Odanacatib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Period 2
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Period 2 title |
Transition to First Extension Study
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Is this the baseline period? |
No | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Odanacatib 50 mg OW | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Odanacatib
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Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||
Other name |
MK-0822
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Arm title
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Placebo | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo for Odanacatib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Period 3
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Period 3 title |
First Extension Double Blind Period
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Is this the baseline period? |
No | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Odanacatib 50 mg OW | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Odanacatib
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Investigational medicinal product code |
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Other name |
MK-0822
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Arm title
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Placebo | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo for Odanacatib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Period 4
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Period 4 title |
First Extension Open Label Period
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Is this the baseline period? |
No | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
|
Odanacatib 50 mg OW | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Odanacatib
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|||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||
Other name |
MK-0822
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Arm title
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Odanacatib 50 mg OW (originally assigned to Placebo) | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Odanacatib
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|||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||
Other name |
MK-0822
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|||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
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|||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Period 5
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Period 5 title |
Transition to Second Extension
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Is this the baseline period? |
No | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||||||||||||||
Arm title
|
Odanacatib 50 mg OW | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Odanacatib
|
|||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||
Other name |
MK-0822
|
|||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
50 mg tablet orally OW
|
|||||||||||||||||||||||||||||||||||||||
Arm title
|
Odanacatib 50 mg OW (originally assigned to Placebo) | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Odanacatib
|
|||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||
Other name |
MK-0822
|
|||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
50 mg tablet orally OW
|
|||||||||||||||||||||||||||||||||||||||
|
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Period 6
|
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Period 6 title |
Second Extension Study
|
|||||||||||||||||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||||||||||||||
Arm title
|
Odanacatib 50 mg OW | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Odanacatib
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Investigational medicinal product code |
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Other name |
MK-0822
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Arm title
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Odanacatib 50 mg OW (originally assigned to Placebo) | |||||||||||||||||||||||||||||||||||||||
Arm description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Odanacatib
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Investigational medicinal product code |
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Other name |
MK-0822
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 mg tablet orally OW
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Baseline characteristics reporting groups
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Reporting group title |
Odanacatib 50 mg OW
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Reporting group description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Odanacatib 50 mg OW
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Reporting group description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Odanacatib 50 mg OW
|
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Reporting group description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Odanacatib 50 mg OW
|
||
Reporting group description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Odanacatib 50 mg OW
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Reporting group description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Odanacatib 50 mg OW (originally assigned to Placebo)
|
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Reporting group description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Odanacatib 50 mg OW
|
||
Reporting group description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Odanacatib 50 mg OW (originally assigned to Placebo)
|
||
Reporting group description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Odanacatib 50 mg OW
|
||
Reporting group description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||
Reporting group title |
Odanacatib 50 mg OW (originally assigned to Placebo)
|
||
Reporting group description |
Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly. Participants also receive 5600 IU Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. |
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End point title |
Base Study: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture | ||||||||||||
End point description |
Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures occurring after baseline were confirmed by quantitative morphometric (QM) and either SQ or binary SQ methodologies. A time-to-event methodology was used: life-table estimates of the proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and at yearly intervals; an interval-censored approach was used to determine incidence rate (number of participants with a morphometric fracture per 100 patient-years of follow-up). The Full-Analysis-Set (FAS) including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) with at least one spine radiograph on treatment (and at baseline) was used for analysis.
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End point type |
Primary
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End point timeframe |
Up to 5 years
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Statistical analysis title |
Odanacatib 50 mg OW vs Placebo. | ||||||||||||
Statistical analysis description |
Generalized linear model for binary data with cloglog link and terms for time interval, treatment, stratum, and geographic region. cloglog link = complementary log log transformation of probability of an event up to the time-point.
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Comparison groups |
Odanacatib 50 mg OW v Placebo
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Number of subjects included in analysis |
13680
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Generalized linear model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.46
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Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.4 | ||||||||||||
upper limit |
0.53 |
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End point title |
Base Study: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated) | ||||||||||||
End point description |
Osteoporotic clinical hip fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided. The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) was used for analysis.
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End point type |
Primary
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End point timeframe |
Up to 5 years
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Statistical analysis title |
Odanacatib 50 mg OW vs Placebo. | ||||||||||||
Statistical analysis description |
The Cox proportional hazards model included terms for treatment, stratum and geographic region.
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Comparison groups |
Odanacatib 50 mg OW v Placebo
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Number of subjects included in analysis |
16071
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.53
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Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
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||||||||||||
lower limit |
0.39 | ||||||||||||
upper limit |
0.71 |
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End point title |
Base Study: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated) | ||||||||||||
End point description |
Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excl. fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anat. sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (# of participants with a fracture per 100 patient-years of follow-up) is provided. The FAS including all rand. participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) was used for analysis.
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End point type |
Primary
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End point timeframe |
Up to 5 years
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||||||||||||
|
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Statistical analysis title |
Odanacatib 50 mg OW vs Placebo. | ||||||||||||
Statistical analysis description |
The Cox proportional hazards model included terms for treatment, stratum and geographic region.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
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Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.77
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
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||||||||||||
lower limit |
0.68 | ||||||||||||
upper limit |
0.87 |
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End point title |
Base Study + First Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture | ||||||||||||
End point description |
Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures occurring after baseline were confirmed by quantitative morphometric (QM) and either SQ or binary SQ methodologies. A time-to-event methodology was used: life-table estimates of the proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and at yearly intervals; an interval-censored approach was used to determine incidence rate (number of participants with a morphometric fracture per 100 patient-years of follow-up). The Full-Analysis-Set (FAS) including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) with at least one spine radiograph on treatment (and at baseline) was used for analysis.
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End point type |
Primary
|
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End point timeframe |
Up to 5 years
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW vs Placebo. | ||||||||||||
Statistical analysis description |
Generalized linear model for binary data with cloglog link and terms for time interval, treatment, stratum, and geographic region. cloglog link = complementary log log transformation of probability of an event up to the time-point.
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Comparison groups |
Odanacatib 50 mg OW v Placebo
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||||||||||||
Number of subjects included in analysis |
13920
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Generalized linear model | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.48
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||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.42 | ||||||||||||
upper limit |
0.55 |
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End point title |
Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated) | ||||||||||||
End point description |
Osteoporotic clinical hip fractures was confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided.
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End point type |
Primary
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||||||||||||
End point timeframe |
Up to 5 years
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW vs Placebo. | ||||||||||||
Statistical analysis description |
The Cox proportional hazards model included terms for treatment, stratum and geographic region.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.52
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
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||||||||||||
lower limit |
0.4 | ||||||||||||
upper limit |
0.67 |
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End point title |
Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated) | ||||||||||||
End point description |
Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur and shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided.
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End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 years
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW vs Placebo. | ||||||||||||
Statistical analysis description |
The Cox proportional hazards model included terms for treatment, stratum and geographic region.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.74
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.66 | ||||||||||||
upper limit |
0.83 |
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End point title |
Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip [1] | |||||||||||||||||||||||||||||||||||||||
End point description |
BMD was measured by dual-energy x-ray absorptiometry (DXA) at the total hip starting at screening & at yearly intervals until the end of study (second ext. study) for all participants who entered the second ext. study. Least squares (LS) means percent change in BMD from orig. baseline are provided through Month 108 (Year 9). At Months 96 (Year 8) & 108 (Year 9), approx. 3% or fewer patients in each treatment group had BMD data, & results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medic. in the base study. The FAS population incl. all rand. patients who took at least one dose of study medication & with necessary on-treatment info. (total hip BMD) was used for analysis (base study + first ext-dbp + second ext).
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End point type |
Primary
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End point timeframe |
Baseline and once yearly up to 10 years
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical comparisons were performed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in Volumetric Bone Mineral Density (vBMD) at the Lumbar Spine Using Quantitative Computed Tomography | ||||||||||||
End point description |
Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 24 (base study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine vBMD) was used for analysis (PN032-Base).
|
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End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg vs Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
8.92
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
3.9 | ||||||||||||
upper limit |
13.93 |
|
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End point title |
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in vBMD at the Lumbar Spine Using Quantitative Computed Tomography | ||||||||||||
End point description |
Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine vBMD) was used for analysis (PN032-Base + Extension).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline, Month 60
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg vs Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
53
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
26.45
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
16.49 | ||||||||||||
upper limit |
36.4 |
|
|||||||||||||||||||||||||
End point title |
Sarcopenia Substudy PN035: Change from Baseline in Appendicular Lean Body Mass (aLBM) | ||||||||||||||||||||||||
End point description |
Sarcopenia is the age-related loss of skeletal muscle mass and associated loss of strength. Progression of sarcopenia was assessed using aLBM as measured by total body DXA. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS for change from baseline at specific time-points including all randomized particpants who took at least one dose of study medication and had the necessary baseline and on-treatment measurements available (aLBM) was used for analysis (PN035).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 4 years
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
504
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
-0.02
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.14 | ||||||||||||||||||||||||
upper limit |
0.09 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
504
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.12 | ||||||||||||||||||||||||
upper limit |
0.12 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
504
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
-0.04
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.17 | ||||||||||||||||||||||||
upper limit |
0.09 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
504
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
-0.21
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.5 | ||||||||||||||||||||||||
upper limit |
0.08 |
|
|||||||||||||||||||||||||
End point title |
Sarcopenia Substudy PN035: Change from Baseline in Short Physical Performance Battery (SPPB) Score | ||||||||||||||||||||||||
End point description |
The SPPB is used to assess physical function in older persons. The SPPB consists of 3 types of physical activities: standing balance, gait speed, and chair rise. Component activities are timed and then reduced to a categorical 0 to 4 scale based on time achieved. A higher composite score (range 0 to 12) indicates an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS for change from baseline at specific time-points including all randomized particpants who took at least one dose of study medication and had the necessary baseline and on-treatment measurements available (SPPB) was used for analysis (PN035).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 4 years
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
504
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.11
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.16 | ||||||||||||||||||||||||
upper limit |
0.38 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
504
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.14
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.15 | ||||||||||||||||||||||||
upper limit |
0.44 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
504
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.19
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.15 | ||||||||||||||||||||||||
upper limit |
0.54 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
504
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.19
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.15 | ||||||||||||||||||||||||
upper limit |
0.54 |
|
|||||||||||||||||||||||||
End point title |
Sarcopenia Substudy PN035: Percent Change from Baseline in Gait Speed | ||||||||||||||||||||||||
End point description |
Gait speed is a component of the SPPB. Participants are asked to walk a distance of 4 meters at their normal pace. The test is performed 2 times, and the walk done in the shortest time is used for scoring. The activity is timed and then reduced to a categorical 0 to 4 scale based on time achieved. Higher scores indicate an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS for change from baseline at specific time-points including all randomized particpants who took at least one dose of study medication and had the necessary baseline and on-treatment measurements available (gait speed) was used for analysis (PN035).
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 4 years.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
501
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.04
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.08 | ||||||||||||||||||||||||
upper limit |
0.15 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
501
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.08
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.06 | ||||||||||||||||||||||||
upper limit |
0.21 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
501
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.03
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.12 | ||||||||||||||||||||||||
upper limit |
0.17 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
501
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.09
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.09 | ||||||||||||||||||||||||
upper limit |
0.28 |
|
|||||||||||||
End point title |
Base study: Rate of Adverse Events | ||||||||||||
End point description |
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 patient-years of follow-up) is provided. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Miettinen & Nurminen method based 95% confidence interval
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in rates | ||||||||||||
Point estimate |
1.52
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.8 | ||||||||||||
upper limit |
4.84 |
|
|||||||||||||
End point title |
Base Study: Rate of Discontinuation from Study Treatment Due to an AE | ||||||||||||
End point description |
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 patient-years of follow-up) is provided. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Miettinen & Nurminen method based 95% confidence interval
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in rates | ||||||||||||
Point estimate |
0.27
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.04 | ||||||||||||
upper limit |
0.58 |
|
|||||||||||||
End point title |
Base Study: Time to First 3-Point Major Adverse Cardiac Event (MACE) Confirmed by Thrombolysis in Myocardial Infarction Study Group (TIMI) Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated 3-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, or 3. non-fatal definite stroke) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.182 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.12
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.95 | ||||||||||||
upper limit |
1.34 |
|
|||||||||||||
End point title |
Base Study: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardigram confirmation was not required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.235 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.18
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.9 | ||||||||||||
upper limit |
1.55 |
|
|||||||||||||
End point title |
Base study + First Extension: Rate of Adverse Events | ||||||||||||
End point description |
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 patient-years of follow-up) is provided. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Miettinen & Nurminen method based 95% Confidence Interval
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in rates | ||||||||||||
Point estimate |
0.88
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.3 | ||||||||||||
upper limit |
4.07 |
|
|||||||||||||
End point title |
Base Study + First Extension: Rate of Discontinuation from Study Treatment Due to an AE | ||||||||||||
End point description |
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 patient-years of follow-up) is provided. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Miettinen & Nurminen method based 95% Confidence Interval
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in rates | ||||||||||||
Point estimate |
0.11
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.16 | ||||||||||||
upper limit |
0.37 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First 3-Point MACE Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated 3-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, or 3. non-fatal definite stroke) was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.029 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.17
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.02 | ||||||||||||
upper limit |
1.36 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardigram confirmation was not required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.178 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.17
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.93 | ||||||||||||
upper limit |
1.46 |
|
||||||||||
End point title |
Second Extension: Number of Participants who Experienced an Adverse Event [2] | |||||||||
End point description |
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation
subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All-Participants-as-Treated population including all patients who took at least one dose of study medication was used for analysis (second extension study).
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Up to 5 years (in the second extension)
|
|||||||||
Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical comparisons were performed for this endpoint. |
||||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Second Extension: Number of Participants Discontinuing Study Treatment Due to an AE [3] | |||||||||
End point description |
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The All-Participants-as-Treated population including all patients who took at least one dose of study medication was used for analysis (second extension).
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Up to 5 years (in the second extension)
|
|||||||||
Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical comparisons were performed for this endpoint. |
||||||||||
|
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Base Study: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated) | ||||||||||||
End point description |
Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided. The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) was used for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW vs Placebo. | ||||||||||||
Statistical analysis description |
The Cox proportional hazards model included terms for treatment, stratum and geographic region.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.28
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.19 | ||||||||||||
upper limit |
0.4 |
|
|||||||||||||
End point title |
Base Study: Yearly Rate of Height Loss | ||||||||||||
End point description |
Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (height) was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and once yearly up to 5 years
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW versus Placebo. | ||||||||||||
Statistical analysis description |
The mixed model contained fixed effects for treatment, region, stratum, treatment-year interaction and random effect intercept and slope (year) and unstructured covariance matrix.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
12343
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.041 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.01
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0 | ||||||||||||
upper limit |
0.03 |
|
||||||||||||||||||||||||||||
End point title |
Base Study: Number of Participants with Height Loss of > 1 cm | |||||||||||||||||||||||||||
End point description |
Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (height loss) was used for analysis (base study).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 5 years
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW versus Placebo. | |||||||||||||||||||||||||||
Statistical analysis description |
Treatment comparison for height loss at any time during the treatment period. The logistic model contained terms for treatment, geographic region and stratum.
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
12310
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
= 0.014 | |||||||||||||||||||||||||||
Method |
Logistic model | |||||||||||||||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||||||||||||||
Point estimate |
0.89
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.81 | |||||||||||||||||||||||||||
upper limit |
0.98 |
|
|||||||||||||||||||||||||||||||
End point title |
Base Study: Percent Change from Baseline in BMD Measurements of the Total Hip | ||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
1.32
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.9 | ||||||||||||||||||||||||||||||
upper limit |
1.75 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
2.49
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
2.37 | ||||||||||||||||||||||||||||||
upper limit |
2.61 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
4.47
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
4.31 | ||||||||||||||||||||||||||||||
upper limit |
4.62 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
6.44
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
6.25 | ||||||||||||||||||||||||||||||
upper limit |
6.64 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
8.62
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
8.11 | ||||||||||||||||||||||||||||||
upper limit |
9.12 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
9.49
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
8.7 | ||||||||||||||||||||||||||||||
upper limit |
10.29 |
|
|||||||||||||||||||||||||||||||
End point title |
Base Study: Percent Change from Baseline in BMD Measurements of the Lumbar Spine | ||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (lumbar spine BMD) was used for analysis (base study).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12744
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
2.96
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
2.47 | ||||||||||||||||||||||||||||||
upper limit |
3.46 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12744
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
4.07
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
3.93 | ||||||||||||||||||||||||||||||
upper limit |
4.22 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12744
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
6.05
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
5.87 | ||||||||||||||||||||||||||||||
upper limit |
6.23 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12744
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
7.84
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
7.62 | ||||||||||||||||||||||||||||||
upper limit |
8.06 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12744
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
9.72
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
9.16 | ||||||||||||||||||||||||||||||
upper limit |
10.27 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12744
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
11.23
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
10.23 | ||||||||||||||||||||||||||||||
upper limit |
12.23 |
|
|||||||||||||||||||||||||||||||
End point title |
Base Study: Percent Change from Baseline in BMD Measurements of the Femoral Neck | ||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (femoral neck BMD) was used for analysis (base study).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13087
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
1.49
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.95 | ||||||||||||||||||||||||||||||
upper limit |
2.03 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13087
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
2.21
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
2.05 | ||||||||||||||||||||||||||||||
upper limit |
2.37 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13087
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
4.38
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
4.19 | ||||||||||||||||||||||||||||||
upper limit |
4.57 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13087
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
6.46
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
6.24 | ||||||||||||||||||||||||||||||
upper limit |
6.68 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13087
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
8.42
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
7.82 | ||||||||||||||||||||||||||||||
upper limit |
9.02 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13087
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
8.53
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
7.54 | ||||||||||||||||||||||||||||||
upper limit |
9.53 |
|
|||||||||||||||||||||||||||||||
End point title |
Base Study: Percent Change from Baseline in BMD Measurements of the Trochanter | ||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (trochanter BMD) was used for analysis (base study).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
1.74
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
1.03 | ||||||||||||||||||||||||||||||
upper limit |
2.46 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
3.5
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
3.31 | ||||||||||||||||||||||||||||||
upper limit |
3.7 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24 | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
6.41
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
6.17 | ||||||||||||||||||||||||||||||
upper limit |
6.65 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36 | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
9.27
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
8.98 | ||||||||||||||||||||||||||||||
upper limit |
9.57 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48 | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
12.44
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
11.66 | ||||||||||||||||||||||||||||||
upper limit |
13.22 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60 | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13086
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
13.81
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
12.58 | ||||||||||||||||||||||||||||||
upper limit |
15.04 |
|
||||||||||||||||||||||||||||
End point title |
Base Study: Percent Change from Baseline in BMD Measurements of the Distal-Third Forearm | |||||||||||||||||||||||||||
End point description |
BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study) in an approximate 10% random subset of participants at selected sites. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (distal one-third radius BMD) was used for analysis (base study).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 5 years
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
1.11
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.67 | |||||||||||||||||||||||||||
upper limit |
1.55 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
1.35
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.85 | |||||||||||||||||||||||||||
upper limit |
1.84 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
1.93
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
1.38 | |||||||||||||||||||||||||||
upper limit |
2.47 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
= 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
2.2
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.89 | |||||||||||||||||||||||||||
upper limit |
3.51 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
= 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
3.5
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
1.46 | |||||||||||||||||||||||||||
upper limit |
5.54 |
|
|||||||||||||||||||||||||
End point title |
Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants | ||||||||||||||||||||||||
End point description |
BMD was measured by DXA in bisphosphonate-intolerant participants at the lumbar spine at randomization, and at yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. Bisphosphontes are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards significance testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Months 6, 60) or results should be viewed with caution as exploratory results (i.e., Month 48).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2243
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
4.02
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
3.67 | ||||||||||||||||||||||||
upper limit |
4.37 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2243
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
5.79
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
5.37 | ||||||||||||||||||||||||
upper limit |
6.2 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2243
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
7.62
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
7.11 | ||||||||||||||||||||||||
upper limit |
8.13 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2243
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
9.51
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
7.96 | ||||||||||||||||||||||||
upper limit |
11.06 |
|
|||||||||||||||||||||||||
End point title |
Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants | ||||||||||||||||||||||||
End point description |
BMD was measured by DXA in bisphosphonate-intolerant participants at the total hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphontes are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards significance testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Months 6, 60) or results should be viewed with caution as exploratory results (i.e., Month 48). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2282
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
2.4
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
2.11 | ||||||||||||||||||||||||
upper limit |
2.68 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2282
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
4.21
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
3.84 | ||||||||||||||||||||||||
upper limit |
4.57 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2282
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
5.86
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
5.41 | ||||||||||||||||||||||||
upper limit |
6.3 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2282
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
8.54
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
7 | ||||||||||||||||||||||||
upper limit |
10.09 |
|
|||||||||||||||||||||||||
End point title |
Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants | ||||||||||||||||||||||||
End point description |
BMD was measured by DXA in bisphosphonate-intolerant participants at the femoral neck-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphontes are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards significance testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Months 6, 60) or results should be viewed with caution as exploratory results (i.e., Month 48). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (femoral neck BMD) was used for analysis (base study).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2283
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
2.21
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
1.83 | ||||||||||||||||||||||||
upper limit |
2.59 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2283
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
4.33
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
3.87 | ||||||||||||||||||||||||
upper limit |
4.78 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2283
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
6.09
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
5.56 | ||||||||||||||||||||||||
upper limit |
6.62 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2283
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
9.08
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
6.97 | ||||||||||||||||||||||||
upper limit |
11.19 |
|
|||||||||||||||||||||||||
End point title |
Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants | ||||||||||||||||||||||||
End point description |
BMD was measured by DXA in bisphosphonate-intolerant participants at the trochanter-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphontes are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards significance testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Months 6, 60) or results should be viewed with caution as exploratory results (i.e., Month 48). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (trochanter BMD) was used for analysis (base study).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12 | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2282
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
3.44
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
2.98 | ||||||||||||||||||||||||
upper limit |
3.9 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2282
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
6.03
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
5.47 | ||||||||||||||||||||||||
upper limit |
6.59 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2282
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
8.49
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
7.81 | ||||||||||||||||||||||||
upper limit |
9.16 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
2282
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
11.76
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
9.15 | ||||||||||||||||||||||||
upper limit |
14.36 |
|
|||||||||||||||||||||||||
End point title |
Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants | ||||||||||||||||||||||||
End point description |
BMD was measured by DXA at the distal one-third radius at rand. and at yearly intervals until the end of study (base study) in an approx. 10% random subset of bisphosphonate-intolerant participants at selected sites. Bisphosphontes are anti-resorptive agents used in treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindic. or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment. Timepoints with a minimum of 50% participant visits were included in the multiplicity adjustment strategy towards signific. testing; therefore, timepoints with fewer participants than threshold were either not analyzed (i.e., Month 60) or results should be viewed with caution as explor. results (i.e., Month 48). The FAS population including all rand. patients who took at least one dose of study medication and having the necessary on-treatment information (distal one-third radius BMD) was used for analysis (base study).
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 5 years
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
= 0.083 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
1.08
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.14 | ||||||||||||||||||||||||
upper limit |
2.31 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
= 0.129 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
1.05
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.31 | ||||||||||||||||||||||||
upper limit |
2.4 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
= 0.104 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
1.21
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-0.25 | ||||||||||||||||||||||||
upper limit |
2.67 | ||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
189
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||
P-value |
= 0.617 | ||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
1.55
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-4.92 | ||||||||||||||||||||||||
upper limit |
8.02 |
|
||||||||||||||||||||||||||||
End point title |
Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation | |||||||||||||||||||||||||||
End point description |
s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (s-CTx) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 4 years
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1247
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-58.99
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-64.68 | |||||||||||||||||||||||||||
upper limit |
-53.3 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1247
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-60.01
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-66.4 | |||||||||||||||||||||||||||
upper limit |
-53.61 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1247
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-46.7
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-53.23 | |||||||||||||||||||||||||||
upper limit |
-40.17 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1247
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-44.67
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-52.62 | |||||||||||||||||||||||||||
upper limit |
-36.72 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1247
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
= 0.05 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-18.73
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-37.44 | |||||||||||||||||||||||||||
upper limit |
-0.01 |
|
||||||||||||||||||||||||||||
End point title |
Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation | |||||||||||||||||||||||||||
End point description |
u-NTx, a biochemical marker of bone resorption, was assessed at rand., Month 6, & at yearly intervals until end of study (base study) in an approx. 10% random subset participants at selected sites. Urine NTx measurements (in bone collagen equivalents [BCE]) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) & the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longitudinal model with terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size). Back-transformed weighted geom. LS means values for percent change from baseline are provided. The per-protocol population incl. all rand. patients who took at least one dose of study medication and having the necessary on-treatment information (u-NTx/Cr) & excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 4 years
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1222
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-51.7
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-56.11 | |||||||||||||||||||||||||||
upper limit |
-47.28 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1222
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-53.59
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-58.39 | |||||||||||||||||||||||||||
upper limit |
-48.79 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1222
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-56.68
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-62.52 | |||||||||||||||||||||||||||
upper limit |
-50.84 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1222
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-59.14
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-66.04 | |||||||||||||||||||||||||||
upper limit |
-52.23 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1222
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-44.54
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-61.72 | |||||||||||||||||||||||||||
upper limit |
-27.36 |
|
||||||||||||||||||||||||||||
End point title |
Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation | |||||||||||||||||||||||||||
End point description |
BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at rand., Month 6, and at yearly intervals until the end of the study (base study) in an approx. 10% random subset participants at selected sites. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population including all rand. patients who took at least one dose of study medication and having the necessary on-treatment information (BSAP) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 4 years
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-14.13
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-17 | |||||||||||||||||||||||||||
upper limit |
-11.27 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-12.01
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-15.22 | |||||||||||||||||||||||||||
upper limit |
-8.79 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-9.29
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-13.45 | |||||||||||||||||||||||||||
upper limit |
-5.13 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-7.64
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-11.87 | |||||||||||||||||||||||||||
upper limit |
-3.41 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
= 0.896 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-0.77
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-12.34 | |||||||||||||||||||||||||||
upper limit |
10.79 |
|
||||||||||||||||||||||||||||
End point title |
Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation | |||||||||||||||||||||||||||
End point description |
P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (P1NP) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (base study).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 4 years
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-29.43
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-33.47 | |||||||||||||||||||||||||||
upper limit |
-25.39 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-25.94
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-30.54 | |||||||||||||||||||||||||||
upper limit |
-21.34 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-16.26
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-21.41 | |||||||||||||||||||||||||||
upper limit |
-11.12 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-12.11
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-18.03 | |||||||||||||||||||||||||||
upper limit |
-6.19 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | |||||||||||||||||||||||||||
Statistical analysis description |
Longitudinal model includes terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS Means weighted for region and stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1284
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
= 0.61 | |||||||||||||||||||||||||||
Method |
Longitudinal | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
-3.34
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-16.12 | |||||||||||||||||||||||||||
upper limit |
9.45 |
|
|||||||||||||
End point title |
Base Study + First Extension + Second Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture | ||||||||||||
End point description |
Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures occurring after baseline were confirmed by quantitative morphometric (QM) and either SQ or binary SQ methodologies. A time-to-event methodology was used: life-table estimates of the proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and at yearly intervals; an interval-censored approach was used to determine incidence rate (number of participants with a morphometric fracture per 100 patient-years of follow-up). The Full-Analysis-Set (FAS) including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study) with at least one spine radiograph on treatment (and at baseline) was used for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 10 years
|
||||||||||||
|
|||||||||||||
Notes [4] - The study was terminated early due to an observed increase in risk of stroke in Protocol MK-0822-018 [5] - The study was terminated early due to an observed increase in risk of stroke in Protocol MK-0822-018 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Second Extension: Incidence of Osteoporotic Clinical Thoracic Vertebral Fracture (Adjudicated) | ||||||||||||
End point description |
Osteoporotic vertebral clinical fractures were confirmed by central adjudic. using radiographic evidence on all symptomatic fractures reported as adverse experiences (excl. fractures of fingers, toes, face, & skull). Vertebral fractures were assessed for all thoracic vertebral levels (T1 to T12). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second ext. study with osteoporotic vertebral clinical fractures is provided. Due to early term. of the study, cumulative incidence using a time-to-event methodology was not assessed across base and ext. studies. The All-Participants-as-Treated Population including all rand. participants who entered the second ext. study & received at least one dose of open-label treatment was used for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (in the second extension)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Second Extension: Incidence of Osteoporotic Clinical Lumbar Vertebral Fracture (Adjudicated) | ||||||||||||
End point description |
Osteoporotic vertebral clinical fractures were confirmed by central adjudic. using radiographic evidence on all symptomatic fractures reported as adverse experiences (excl. fractures of fingers, toes, face, & skull). Vertebral fractures were assessed for all lumbar vertebral levels (L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second ext. study with osteoporotic vertebral clinical fractures is provided. Due to early termination of the study, cumulative incidence using a time-to-event methodology was not assessed across base and ext. studies. The All-Participants-as-Treated Population incl. all rand. participants who entered the second ext. study and received at least one dose of open-label treatment was used for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (in the second extension)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Second Extension: Incidence of Osteoporotic Clinical Fracture of Any Type (Adjudicated) | ||||||||||||
End point description |
Osteoporotic clinical fractures of any type were confirmed by central adjudic. using radiogr. evidence on all symp. fractures reported as adverse experiences (excl. fractures of fingers, toes, face, skull). Non-vertebral fractures were assessed across mult. anat. sites incl. clavicle, dist. femur/shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, wrist; Vert. fractures assessed acr. all levels (C7/T1-12/L1-5) were incl. in analysis. Osteoporotic (fragility) fractures did not incl. fractures with traumatic/path. etiologies. Clin. fracture was defined as a fracture with related symptoms (eg, pain). The incid. proportion (cumul. incidence) of participants in 2nd ext. study with at least one osteoporotic clin. fracture of any type is provided. The All-Participants-as-Treated Popul. incl. all rand. participants who entered 2nd ext. study & received at least one dose of open-label treatment was used for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (in the second extension)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Base Study + First Extension + Second Extension: Change in Height From Baseline Stature | ||||||||||||
End point description |
Height was measured by wall-mounted stadiometer at randomization and at yearly intervals across the base study and the two extension studies.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and once yearly up to 10 years
|
||||||||||||
|
|||||||||||||
Notes [6] - The study was terminated early due to an observed increase in risk of stroke in Protocol MK-0822-018 [7] - The study was terminated early due to an observed increase in risk of stroke in Protocol MK-0822-018 |
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||
End point title |
Base Study + First Extension + Second Extension: Percent Change from Baseline in BMD Measurements of the Lumbar Spine | |||||||||||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA at lumbar spine starting at rand. & yearly interv. until end of study (2nd ext. study) for all participants who entered 2nd ext. study. Measurements were made on at least 3 vert. for all time points; vert. with fractures were excluded. At M96/108, approx. 3% or fewer patients in each tx group had BMD data & results at those time points should be viewed with caution. NOTE: Mean % change in BMD from baseline in participants originally rand. to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in base study. A longit. model with terms for tx, stratum, region & interaction b/w. tx & time as fixed effects (LS means weighted for region & stratum size) was used. The FAS popul. consisted of all rand. participants who entered 2nd ext. study & received at least one dose of open-label tx & had necessary on-tx info. (lumbar spine BMD).
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 10 years
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||
End point title |
Base Study + First Extension + Second Extension: Percent Change from Baseline in BMD Measurements of the Femoral Neck | |||||||||||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA at fem. neck starting at screening & yearly interv. until end of study (2nd ext. study) for all participants who entered 2nd ext. study. LS means % change in BMD from original baseline (BL) are provided through M108. At M96/108, approx. 3% or fewer patients in each tx group had BMD data & results at those time points should be viewed with caution. NOTE: The mean % change in BMD from BL in participants originally rand. to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in base study. A longit. model with terms for tx, stratum, region & interaction b/w tx & time as fixed effects (LS means weighted for region & stratum size) was used for analysis. The FAS popul. consisted of all rand. participants who entered 2nd ext. study & received at least 1 dose of open-label treatment & had necessary on-treatment info. (fem. neck BMD).
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 10 years
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||
End point title |
Base Study + First Extension + Second Extension: Percent Change from Baseline in BMD Measurements of the Trochanter | |||||||||||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA at the trochanter starting at screening & at yearly intervals until end of study (2nd ext. study) for all participants who entered the 2nd ext. study. LS means % change in BMD from original BL are provided through M108. At M96/108, approx. 3% or fewer patients in each tx group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean % change in BMD from BL in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in base study. A longit. model with terms for treatment, stratum, region & interaction b/w tx & time as fixed effects (LS means weighted for region & stratum size) was used. The FAS popul. consisted of all rand. participants who entered 2nd ext. study & received at least one dose of open-label tx & had the necessary on-tx info. (trochanter BMD).
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 10 years
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated) | ||||||||||||
End point description |
Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 patient-years of follow-up) is provided. The FAS including all randomized participants who took at least one dose of study medication with follow-up from start of prime therapy to study termination (base study + first extension) was used for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW vs Placebo. | ||||||||||||
Statistical analysis description |
The Cox proportional hazards model included terms for treatment, stratum and geographic region.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.33
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.24 | ||||||||||||
upper limit |
0.45 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Fracture (Adjudicated) | ||||||||||||
End point description |
Osteoporotic clinical fractures (combining vertebral & non-vert.) were confirmed by central adjudic. using radiographic evidence on all symp. fractures reported as adverse experiences (excl. fractures of fingers, toes, face, skull). Vert. fractures were assessed for all levels (C7/T1-12/L1-5). Non-vert. fractures were assessed acr. multiple anat. sites incl. clav., distal femur/shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, wrist. Osteoporotic (fragility) fractures did not incl. fractures with traumatic or pathol. etiologies. A clin. fracture was defined as fracture with related symp. (eg, pain). A time-to-event methodol. was used to eval. results: the incid. rate of participants with fracture (# of participants with fracture per 100 patient-years of follow-up) is provided. The FAS incl. all rand. participants who took at least 1 dose of study medication with follow-up from start of prime therapy to study term. (base study + first ext.) was used for analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW vs Placebo. | ||||||||||||
Statistical analysis description |
The Cox proportional hazards model included terms for treatment, stratum and geographic region.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.67
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.6 | ||||||||||||
upper limit |
0.75 |
|
|||||||||||||||||||||||||||||||
End point title |
Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Total Hip | ||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (total hip BMD) was used for analysis (base study + first extension-dbp).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
1.34
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.94 | ||||||||||||||||||||||||||||||
upper limit |
1.74 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
2.5
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
2.38 | ||||||||||||||||||||||||||||||
upper limit |
2.62 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
4.47
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
4.31 | ||||||||||||||||||||||||||||||
upper limit |
4.62 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
6.46
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
6.26 | ||||||||||||||||||||||||||||||
upper limit |
6.65 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
8.48
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
8.24 | ||||||||||||||||||||||||||||||
upper limit |
8.73 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
10.29
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
9.99 | ||||||||||||||||||||||||||||||
upper limit |
10.59 |
|
|||||||||||||||||||||||||||||||
End point title |
Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Lumbar Spine | ||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (lumbar spine BMD) was used for analysis (base study + first extension-dbp).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12595
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
2.9
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
2.4 | ||||||||||||||||||||||||||||||
upper limit |
3.39 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12595
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
4.01
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
3.87 | ||||||||||||||||||||||||||||||
upper limit |
4.15 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12595
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
5.93
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
5.75 | ||||||||||||||||||||||||||||||
upper limit |
6.11 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12595
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
7.7
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
7.48 | ||||||||||||||||||||||||||||||
upper limit |
7.91 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12595
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
9.34
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
9.08 | ||||||||||||||||||||||||||||||
upper limit |
9.61 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
12595
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
10.87
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
10.55 | ||||||||||||||||||||||||||||||
upper limit |
11.19 |
|
|||||||||||||||||||||||||||||||
End point title |
Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Femoral Neck | ||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (femoral neck BMD) was used for analysis (base study + first extension-dbp).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
1.47
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.92 | ||||||||||||||||||||||||||||||
upper limit |
2.01 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
2.21
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
2.05 | ||||||||||||||||||||||||||||||
upper limit |
2.37 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
4.39
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
4.2 | ||||||||||||||||||||||||||||||
upper limit |
4.57 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
6.5
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
6.28 | ||||||||||||||||||||||||||||||
upper limit |
6.72 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
8.29
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
8.02 | ||||||||||||||||||||||||||||||
upper limit |
8.57 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
10.05
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
9.72 | ||||||||||||||||||||||||||||||
upper limit |
10.38 |
|
|||||||||||||||||||||||||||||||
End point title |
Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Trochanter | ||||||||||||||||||||||||||||||
End point description |
BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (trochanter BMD) was used for analysis (base study + first extension-dbp).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Month 6, and once yearly up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 6. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
1.74
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
1.06 | ||||||||||||||||||||||||||||||
upper limit |
2.42 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
3.5
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
3.31 | ||||||||||||||||||||||||||||||
upper limit |
3.7 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24 | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
6.41
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
6.16 | ||||||||||||||||||||||||||||||
upper limit |
6.65 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
9.25
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
8.95 | ||||||||||||||||||||||||||||||
upper limit |
9.54 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
12.14
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
11.76 | ||||||||||||||||||||||||||||||
upper limit |
12.51 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60. | ||||||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
||||||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
13099
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Longitudinal model | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||||||||
Point estimate |
14.56
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
14.11 | ||||||||||||||||||||||||||||||
upper limit |
15.01 |
|
||||||||||||||||||||||||||||
End point title |
Base Study + First Extension: Percent Change from Baseline in BMD Measurements of the Distal-Third Forearm | |||||||||||||||||||||||||||
End point description |
BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study + first extension-dbp) in an approximate 10% random subset of participants at selected sites. The FAS population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (distal one-third radius BMD) was used for analysis (base study + first extension-dbp).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline and once yearly up to 5 years
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 12. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
1.1
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.66 | |||||||||||||||||||||||||||
upper limit |
1.54 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 24. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
1.36
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.87 | |||||||||||||||||||||||||||
upper limit |
1.85 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 36. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
1.96
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
1.42 | |||||||||||||||||||||||||||
upper limit |
2.5 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 48. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
2.18
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
1.4 | |||||||||||||||||||||||||||
upper limit |
2.96 | |||||||||||||||||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo at Month 60. | |||||||||||||||||||||||||||
Statistical analysis description |
The longitudinal model includes terms for treatment, stratum, region & interaction between treatment & time as fixed effects (LS means weighted for region & stratum size).
|
|||||||||||||||||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1397
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Longitudinal model | |||||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||||||||
Point estimate |
2.33
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
1.54 | |||||||||||||||||||||||||||
upper limit |
3.11 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography | ||||||||||||
End point description |
Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 24 was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip cortical vBMD) was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.76
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.43 | ||||||||||||
upper limit |
4.1 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in Areal BMD (aBMD) of the Lumbar Spine Using DXA | ||||||||||||
End point description |
aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 24 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine aBMD) was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
109
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
5.55
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
4.06 | ||||||||||||
upper limit |
7.05 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Total Hip Using DXA | ||||||||||||
End point description |
aBMD was measured at the total hip at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip aBMD) was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
3.63
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
2.35 | ||||||||||||
upper limit |
4.9 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA | ||||||||||||
End point description |
aBMD was measured at the femoral neck at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (femoral neck aBMD) was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.005 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.79
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.86 | ||||||||||||
upper limit |
4.72 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Trochanter Using DXA | ||||||||||||
End point description |
aBMD was measured at the trochanter at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (trochanter aBMD) was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
5.65
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
3.79 | ||||||||||||
upper limit |
7.5 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Distal-Third Forearm Using DXA | ||||||||||||
End point description |
aBMD was measured at the the distal one-third radius at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (trochanter aBMD) was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
104
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.016 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
1.67
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.32 | ||||||||||||
upper limit |
3.01 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in s-CTx After Log-Transformation | ||||||||||||
End point description |
s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population including all randomized patients who took at least one dose of study medication and having the necessary on-treatment information (s-CTx) and excluding participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS Means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
81
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-62.25
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-79.99 | ||||||||||||
upper limit |
-44.5 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in u-NTx/Cr Ratio After Log-Transformation | ||||||||||||
End point description |
u-NTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline & M24 in an approx. 10% random subset participants at selected sites in P018 base study who were additionally included in imaging substudy PN032-base study. Urine NTx measurements (in BCE) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) & the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longit. model with terms for tx, stratum, & interaction b/w tx & time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for % change from baseline are provided. The per-protocol population incl. all rand. participants who took at least one dose of study medication & having necessary on-tx information (u-NTx/Cr) & excl. participants and/or data points that represent clinically important deviations from protocol-specified criteria was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS Means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
81
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-64.43
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-87.8 | ||||||||||||
upper limit |
-41.07 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in BSAP After Log-Transformation | ||||||||||||
End point description |
BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at baseline & M24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for tx, stratum, & interaction between tx & time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided. The per-protocol population incl. all rand. patients who took at least one dose of study medication & having the necessary on-tx information (BSAP) & excl. participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS Means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
81
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-25.02
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-35.92 | ||||||||||||
upper limit |
-14.12 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base: Percent Change From Baseline in P1NP After Log-Transformation | ||||||||||||
End point description |
P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at baseline and Month 24 in an approx. 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction change from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, & interaction b/w treatment & time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for % change from baseline are provided. The per-protocol population including all rand. patients who took at least one dose of study medication & having the necessary on-treatment information (P1NP) & excl. participants and/or data points that represent clinically important deviations from the protocol-specified criteria was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum and interaction between treatment and time as fixed effects (LS Means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
81
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-26.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-42.56 | ||||||||||||
upper limit |
-10.83 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography | ||||||||||||
End point description |
Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip cortical vBMD) was used for analysis (PN032-Base).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 60
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
59
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
8.53
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
5.79 | ||||||||||||
upper limit |
11.28 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Lumbar Spine Using DXA | ||||||||||||
End point description |
aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 60 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (lumbar spine aBMD) was used for analysis (PN032-Base + Extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 60
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
73
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
11.08
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
8.41 | ||||||||||||
upper limit |
13.74 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Total Hip Using DXA | ||||||||||||
End point description |
aBMD was measured at the total hip at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (total hip aBMD) was used for analysis (PN032-Base + Extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 60
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
73
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
10.41
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
8.05 | ||||||||||||
upper limit |
12.78 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA | ||||||||||||
End point description |
aBMD was measured at the femoral neck at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (femoral neck aBMD) was used for analysis (PN032-Base + Extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 60
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
73
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
9.98
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
6.91 | ||||||||||||
upper limit |
13.06 |
|
|||||||||||||
End point title |
Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Trochanter Using DXA | ||||||||||||
End point description |
aBMD was measured at the trochanter at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size). The FAS including consisting of all randomized participants who took at least one dose of blinded study treatment and have a baseline and at least one on-treatment measurement available (trochanter aBMD) was used for analysis (PN032-Base + Extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Month 60
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Longitudinal model with terms for treatment, stratum (prior vertebral fracture (yes/no)) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
73
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Longitudinal model | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
14.94
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
11.29 | ||||||||||||
upper limit |
18.59 |
|
|||||||||||||
End point title |
Base Study: Time to First 4-Point MACE Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated 4-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, 3. non-fatal definite stroke, or 4. hospitalization for unstable angina) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.181 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.12
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.95 | ||||||||||||
upper limit |
1.32 |
|
|||||||||||||
End point title |
Base Study: Time to First All-Cause Death Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated all-cause death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region.
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.102 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.13
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.98 | ||||||||||||
upper limit |
1.3 |
|
|||||||||||||
End point title |
Base Study: Time to First Cardiovascular Death Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated cardiovascular death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.277 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.16
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.89 | ||||||||||||
upper limit |
1.52 |
|
|||||||||||||
End point title |
Base Study: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated fatal or non-fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.256 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.82
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.58 | ||||||||||||
upper limit |
1.15 |
|
|||||||||||||
End point title |
Base Study: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.794 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.86
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.29 | ||||||||||||
upper limit |
2.57 |
|
|||||||||||||
End point title |
Base Study: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated fatal or non-fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.034 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.32
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.02 | ||||||||||||
upper limit |
1.7 |
|
|||||||||||||
End point title |
Base Study: Time to First Fatal Stroke Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.081 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.91
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.92 | ||||||||||||
upper limit |
3.97 |
|
|||||||||||||
End point title |
Base Study: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated hospitalization for unstable angina was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.857 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.06
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.59 | ||||||||||||
upper limit |
1.89 |
|
|||||||||||||
End point title |
Base Study: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardigram confirmation was required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.606 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.76 | ||||||||||||
upper limit |
1.59 |
|
|||||||||||||
End point title |
Base Study: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated any reported episode of atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were included and electrocardigram confirmation was not required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.074 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.25
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.98 | ||||||||||||
upper limit |
1.6 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First 4-Point MACE Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated 4-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, 3. non-fatal definite stroke, or 4. hospitalization for unstable angina) was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.062 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.14
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.99 | ||||||||||||
upper limit |
1.31 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First All-Cause Death Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated all-cause death was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.341 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.05
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.95 | ||||||||||||
upper limit |
1.17 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First Cardiovascular Death Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated cardiovascular death was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.246 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.13
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.92 | ||||||||||||
upper limit |
1.4 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated fatal or non-fatal definite myocardial infarction was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.675 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.94
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.7 | ||||||||||||
upper limit |
1.26 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated fatal definite myocardial infarction was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.638 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.32 | ||||||||||||
upper limit |
2.03 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated fatal or non-fatal definite stroke was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.005 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.37
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.1 | ||||||||||||
upper limit |
1.71 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First Fatal Stroke Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated fatal definite stroke was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.114 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.61
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.89 | ||||||||||||
upper limit |
2.9 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated hospitalization for unstable angina was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.366 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.79
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.47 | ||||||||||||
upper limit |
1.33 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardigram confirmation was required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study + first extension).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.198 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.23
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.9 | ||||||||||||
upper limit |
1.68 |
|
|||||||||||||
End point title |
Base Study + First Extension: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication | ||||||||||||
End point description |
The time to first TIMI-adjudicated any reported episode of atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were included and electrocardigram confirmation was not required. Results are expressed as number of participants with an event per 100 patient-years of follow-up. Results from MK-0822-083, a follow up study to the MK-0822-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are included. The All-Participants-as-Treated population including all randomized participants who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 5 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Statistical analysis description |
Cox proportional hazards model with terms for treatment, stratum and geographic region
|
||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.059 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.22
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.99 | ||||||||||||
upper limit |
1.5 |
|
|||||||||||||
End point title |
Base Study: Incidence Rate of Femoral Shaft Fractures Confirmed by Adjudication | ||||||||||||
End point description |
The incidence rate of femoral shaft fracture events (including both atypical and non-atypical; of any etiology including traumatic) confirmed by adjudication was determined for the base study. Results are expressed as number of participants with an event per 100 patient-years of follow-up. The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study).
|
||||||||||||
End point type |
Post-hoc
|
||||||||||||
End point timeframe |
Up to 4 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
Miettinen & Nurminen | ||||||||||||
Parameter type |
Difference in rates | ||||||||||||
Point estimate |
0.04
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.01 | ||||||||||||
upper limit |
0.09 |
|
|||||||||||||
End point title |
Base Study: Incidence Rate of Atypical Femoral Shaft Fractures Confirmed by Adjudication | ||||||||||||
End point description |
Atypical subtrochanteric/diaphyseal femoral fractures (AFF) are an uncommon type of low-energy (eg, osteoporotic) femoral shaft fracture of unclear causation infrequently reported in osteoporotic persons treated with long-term anti-resorptive therapy (eg, bisphosphonates). All femoral (femur, femur-distal, femur-shaft) fractures in the base study were adjudicated against both ASBMR 2010 and 2013 criteria . All 5 major features (ie, location along femoral shaft, no/minimal trauma, transverse/short oblique fracture, non-comminuted, complete/incomplete fracture) were required for ASBMR 2010 AFF case definition; while 4 of 5 major features (ie, no/minimal trauma, substantially transverse orientation at cortical origin with possible oblique orientation medially, non-comminuted/minimally comminuted, complete/incomplete fracture, localized periosteal reaction of lateral cortex) with requirement for location along femoral shaft were required for ASBMR 2013 AFF case definition.
|
||||||||||||
End point type |
Post-hoc
|
||||||||||||
End point timeframe |
Up to 4 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
Miettinen & Nurminen | ||||||||||||
Parameter type |
Difference in rates | ||||||||||||
Point estimate |
0.02
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.01 | ||||||||||||
upper limit |
0.05 |
|
|||||||||||||
End point title |
Base Study + First Extension: Incidence Rate of Femoral Shaft Fractures Confirmed by Adjudication | ||||||||||||
End point description |
The incidence rate of femoral shaft fracture events (including both atypical and non-atypical; of any etiology including traumatic) confirmed by adjudication was determined for the base study + first extension. Results are expressed as number of participants with an event per 100 patient-years of follow-up.
|
||||||||||||
End point type |
Post-hoc
|
||||||||||||
End point timeframe |
Up to 4 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
Miettinen & Nurminen | ||||||||||||
Parameter type |
Difference in rates | ||||||||||||
Point estimate |
0.06
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.03 | ||||||||||||
upper limit |
0.11 |
|
|||||||||||||
End point title |
Base Study + First Extension: Incidence Rate of Atypical Femoral Shaft Fractures Confirmed by Adjudication | ||||||||||||
End point description |
Atypical subtrochanteric/diaphyseal femoral fractures (AFF) are an uncommon type of low-energy (eg, osteoporotic) femoral shaft fracture of unclear causation infrequently reported in osteoporotic persons treated with long-term anti-resorptive therapy (eg, bisphosphonates). All femoral (femur, femur-distal, femur-shaft) fractures in the base study + first extension were adjudicated against both ASBMR 2010 & 2013 criteria. All 5 major features (ie, location along femoral shaft, no/minimal trauma, transverse/short oblique fracture, non-comminuted, complete/incomplete fracture) were required for ASBMR 2010 AFF case definition; while 4 of 5 major features (ie, no/minimal trauma, substantially transverse orientation at cortical origin with possible oblique orientation medially, non-comminuted/minimally comminuted, complete/incomplete fracture, localized periosteal reaction of lateral cortex) with requirement for location along femoral shaft were required for ASBMR 2013 AFF case definition.
|
||||||||||||
End point type |
Post-hoc
|
||||||||||||
End point timeframe |
Up to 4 years (Data cutoff April 2016)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Odanacatib 50 mg OW - Placebo | ||||||||||||
Comparison groups |
Odanacatib 50 mg OW v Placebo
|
||||||||||||
Number of subjects included in analysis |
16071
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
Miettinen & Nurminen | ||||||||||||
Parameter type |
Difference in rates | ||||||||||||
Point estimate |
0.03
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.02 | ||||||||||||
upper limit |
0.06 |
|
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Adverse events information
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Timeframe for reporting adverse events |
Up to 10 years
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Adverse event reporting additional description |
The All-Participants-as-Treated population including all randomized patients who took at least one dose of study medication was used for analysis (base study + first extension; second extension).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.1
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Reporting groups
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Reporting group title |
Base Study + First Extension: Odanacatib 50 mg OW
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Reporting group description |
Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total). Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Base Study + First Extension: Placebo
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Reporting group description |
Participants receive blinded placebo to 10 mg of odanacatib weekly over the course of the base study and first extension study (5 years total). Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Second Extension: Odanacatib 50 mg OW
|
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Reporting group description |
Participants receive 50 mg of open-label odanacatib weekly for 5 years in the second extension study after having previously received 50 mg of blinded odanacatib weekly in the base study and first extension study (5 years total). Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Second Extension: Odanacatib 50 mg OW (Placebo)
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Reporting group description |
Participants receive 50 mg of open-label odanacatib weekly for 5 years in the second extension study after having previously received blinded placebo to 50 mg of odanacatib weekly in the base study and first extension study (5 years total). Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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03 Aug 2008 |
Amendment 1; applicable to MK-0822-018 Base Study. |
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06 Aug 2009 |
Amendment 1: applicable to MK-0822-032 Imaging Substudy-Base |
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14 Sep 2009 |
Amendment 1: applicable to MK-0822-035 Imaging Substudy |
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27 Apr 2010 |
Amendment 2: applicable to MK-0822-018 Base Study. |
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25 Apr 2011 |
Amendment 10: defined Extension 1 to MK-0822-018 Base Study. |
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11 Oct 2011 |
Amendment 3: applicable to MK-0822-018 Base Study. |
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11 Oct 2011 |
Amendment 10: defined Extension to MK-0822-032 Imaging Substudy-Base. |
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07 Mar 2012 |
Amendment 4: applicable to MK-0822-018 Base Study. |
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08 Jan 2013 |
Amendment 5: applicable to MK-0822-018 Base Study. |
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09 Jan 2013 |
Amendment 20: defined Extension 2 to MK-0822-018 Base + Extension 1 Study. |
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24 Jun 2013 |
Amendment 6: applicable to MK-0822-018 Base Study. |
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22 Nov 2013 |
Amendment 11: applicable to MK-0822-032 Imaging Substudy-Extension. |
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22 Jul 2014 |
Amendment 21: applicable to MK-0822-018 Extension 2 Study. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |