Osteoporosis
Conditions
Brief summary
This is a 1-year base study with a 1-year extension to examine the effects of a new experimental medication (odanacatib \[MK-0822\]) on postmenopausal osteoporosis. This study will enroll approximately 375 postmenopausal women, and randomly assign them to 4 different doses of odanacatib or to placebo. Measurements performed during the study include: bone mineral density scans, spine x-rays, laboratory blood and urine tests, height measurements and optional bone biopsies (at the end of 2 years).
Detailed description
Study Extension: Participants who completed 12 months of the base study and 12 months of the first extension were invited to continue in three additional extensions: MK0-822-004-10, which extended the study to 36 months, MK-0822-004-20 (NCT00112437) which extended the study to 60 months, and MK-0822-004-30 (NCT00112437), which extended the study to 120 months. * In the first extension, participants continued to receive the same treatment they received in the 12-month base study. * In the second extension, participants were re-randomized to odanacatib 50 mg OW or placebo OW for 12 months. * In the third extension, participants who were initially randomized to odanacatib 3 mg or placebo OW in the base study received odanacatib 50 mg weekly in Years 4 and 5; all other participants remained on the same treatment they were during Year 3. * In the fourth extension, all participants received odanacatib weekly in Years 6-10. Study arms for extensions include only odanacatib 50 mg and placebo for the first two extensions and odanacatib 50 mg only for the third extension. Extension Studies: MK-0822-004-10 (NCT00112437) Extension: Participant has participated in and completed 24 months of treatment in the base study MK-0822-004-20 (NCT00112437) Extension: Participant participated in and completed 36 months of treatment in base and extension studies. MK-0822-004-30 (NCT00112437) Extension: Participant participated in and completed 60 months of treatment in the base and extension studies.
Interventions
DRUGOdanacatib
Odanacatib 3 mg, once weekly for 24 months
DIETARY_SUPPLEMENTVitamin D3
Vitamin D3, two 2800 IU weekly throughout the study
DIETARY_SUPPLEMENTCalcium Carbonate
Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
DRUGPlacebo
Placebo to Odanacatib 3 mg, 10 mg, 25 mg, or 50 once weekly for 24 months
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal for 5 or more years, defined as no menses for at least 5 years OR at least 5 years status post bilateral oophorectomy * Bone mineral density T-score at the hip or spine of -2.0 or less * Spinal anatomy suitable for dual-energy x-ray absorptiometry (DXA). At the lumbar spine, there is no evidence of vertebral fracture in at least 3 vertebrae in the L1 to L4 region on baseline spine films. (Significant scoliosis, bony trauma, degenerative joint disease, and sequelae of orthopedic procedures that result in anatomy that is unsuitable for accurate bone densitometry must be absent from the lumbar spine.) * At least one hip must be evaluable by DXA (e.g., contain no hardware from orthopedic procedures) * In a state of general health allowing for successful completion of the trial * Agreement to not use any medications to treat osteoporosis during the study
Exclusion criteria
* History of prior osteoporotic fracture (unless declined treatment with or was ineligible for osteoporosis therapy) * Past treatment with osteoporosis medications, steroids, hormone replacement, as well as various other medications that affect bone may be exclusionary. (Different
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | Baseline and 12 months | Percentage change in lumbar spine BMD (relative to baseline) at 12 Months. |
| Percentage Change From Baseline in Lumbar Spine BMD at 24 Months | Baseline and 24 months | Percentage change in lumbar spine BMD (relative to baseline) at 24 Months. |
| Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | Baseline and 36 months | Percentage change in lumbar spine BMD (relative to baseline) at 36 months |
| Percentage Change From Baseline in Lumbar Spine BMD at 60 Months | Baseline and Month 60 | Percentage change from baseline in lumbar spine BMD at 60 months. |
| Percentage Change From Baseline in Lumbar Spine BMD at 120 Months | Baseline and Month 120 | Percentage change from baseline in lumbar spine BMD at 120 Months. |
| Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months) | Years 6-10 (up to 60 months, up to 14 days after the last dose of study drug) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
| Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months) | Years 6-10 (up to 60 months) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months | Baseline and 12 months | Back-transformation (geometric mean) of the Least Squares Mean of the log-values percentage change from baseline in biochemical marker of bone turnover (urinary total deoxypyridinolines (u-DPyr)) (relative to baseline) at 12 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months | Baseline and 12 months | Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase (s-BSAP)), at 12 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months | Baseline and 12 months | Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change in Biochemical Marker of Bone turnover (serum N-terminal propeptide of Type 1 collagen (s-P1NP) (relative to baseline) at 12 Months |
| Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months | Baseline and 24 months | Percentage change in total hip Bone Mineral Density (relative to baseline) at 24 Months |
| Percentage Change From Baseline in Femoral Neck BMD at 24 Months | Baseline and 24 months | Percentage change in femoral neck Bone Mineral Density (relative to baseline) at 24 Months |
| Percentage Change From Baseline in Trochanter BMD at 24 Months | Baseline and 24 months | Percentage change from baseline in trochanter BMD (relative to baseline) at 24 Months |
| Percentage Change From Baseline in Total Body BMD at 24 Months | Baseline and 24 months | Percentage change in total body BMD (relative to baseline) at 24 Months |
| Percentage Change From Baseline in Distal Forearm BMD at 24 Months | Baseline and 24 months | Percentage change in distal forearm BMD (relative to baseline) at 24 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months | Baseline and 24 months | Back-transformation (geometric mean) of the Least Squares Mean of the log-values percentage change from baseline in biochemical marker of bone turnover (u-NTx) (relative to baseline) at 24 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months | Baseline and 24 months | Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum C-telopeptides of Type 1 collagen (s-CTx)) (relative to baseline) at 24 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months | Baseline and 24 months | Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary total deoxypyridinolines (u-DPyr)) (relative to baseline) at 24 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months | Baseline and 24 months | Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase (s-BSAP)) (relative to baseline) at 24 Months |
| Percentage Change From Baseline in Total Hip BMD at 12 Months | Baseline and 12 months | Percentage change in total hip BMD (relative to baseline) at 12 months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months | Baseline and 24 months | Back-transformation (geometric mean) of the least squares mean of the log-values percentage change from baseline in biochemical marker of bone turnover (s-P1NP) (relative to baseline) at 24 months |
| Percentage Change From Baseline in Total Hip BMD at 36 Months | Baseline and 36 months | Percentage change in total hip BMD (relative to baseline) at 36 months |
| Percentage Change From Baseline in Trochanter BMD at 36 Months | Baseline and 36 months | Percentage change in trochanter BMD (relative to baseline) at 36 months |
| Percentage Change From Baseline in Total Body BMD at 36 Months | Baseline and 36 months | Percentage change from baseline in total body BMD (relative to baseline) at 36 Months |
| Percentage Change From Baseline in Distal Forearm BMD at 36 Months | Baseline and 36 months | Percentage change in distal forearm BMD (relative to baseline) at 36 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | Baseline and 36 months | Percentage change from baseline in biochemical marker of bone turnover (u-NTx) at 36 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | Baseline and 36 months | Percentage change from baseline in biochemical marker of bone turnover (s-CTx) at 36 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | Baseline and 36 months | Percentage change from baseline in biochemical marker of bone turnover u-DPyr at 36 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | Baseline and 36 months | Geometric Mean Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase \[s-BSAP\]) at 36 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | Baseline and 36 months | Percentage change from baseline in biochemical marker of bone turnover (serum N-terminal propeptide of Type 1 collagen \[s-P1NP\]) at 36 months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | Baseline and 36 months | Percentage change from baseline in biochemical marker of bone turnover (serum bone tartrate-resistant acid phosphatase isoform 5b \[TRAP 5-b\]) at 36 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | Baseline and 36 months | Percentage change from baseline in biochemical marker of bone turnover (serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen \[1-CTP\]) at 36 Months |
| Percentage Change From Baseline in Femoral Neck BMD at 36 Months | Baseline and 36 months | Percentage change in femoral neck BMD (relative to baseline) at 36 Months |
| Percentage Change From Baseline in Femoral Neck BMD at 12 Months | Baseline and 12 months | Percentage change in femoral neck BMD (relative to baseline) at 12 months |
| Percentage Change From Baseline in Trochanter BMD at 12 Months | Baseline and 12 Months | Percentage change in trochanter BMD (relative to baseline) at 12 months |
| Percentage Change From Baseline in Total Body BMD at 12 Months | Baseline and 12 Months | Percentage change in total body BMD (relative to baseline) at 12 months |
| Percentage Change From Baseline in Distal Forearm BMD at 12 Months | Baseline and 12 Months | Percentage change in distal forearm BMD (relative to baseline) at 12 months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months | Baseline and 12 Months | Back-transformation (geometric mean) of the Least Squares (LS) Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary N-telopeptides of Type I collagen (u-NTx)) at 12 Months |
| Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months | Baseline and 12 Months | Back-transformation (geometric mean) of the Least Squares (LS) Mean of the log-values Percentage change from baseline in Biochemical Marker of Bone turnover (serum C-telopeptides of Type 1 collagen (s-CTx)) at 12 Months. |
Participant flow
Recruitment details
Approximately 375 participants were recruited from June 2005 to December 2005. Investigators used one or more of the following recruitment methods: Investigator Patient/Subject Database or Medical Records, Investigator's Local Recruitment/Advertising, Other Health Professional and, Physician Referral (Primary/Specialist/Family Doctor).
Pre-assignment details
Participants entered screening followed by a 3-week placebo run-in. All took vitamin D3, 5600 IU once weekly, those with average daily calcium intakes \<1000 mg took calcium 500 mg/day as calcium carbonate. Participants were excluded from the active treatment based on predetermined exclusion criteria (Bone Mineral Density and laboratory results).
Participants by arm
| Arm | Count |
|---|---|
| Placebo-Base One placebo tablet once a week | 83 |
| Odanacatib 3 Mg-Base One odanacatib 3 mg tablet once a week | 82 |
| Odanacatib 10 Mg-Base One odanacatib 10 mg tablet once a week | 77 |
| Odanacatib 25 Mg-Base One odanacatib 25 mg tablet once a week | 79 |
| Odanacatib 50 Mg-Base One odanacatib 50 mg tablet once a week | 78 |
| Total | 399 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 | FG025 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Year 1 (12-Month Base Study) | Adverse Event | 9 | 10 | 6 | 4 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 1 (12-Month Base Study) | DXA was lower by more than 8% | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 1 (12-Month Base Study) | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 1 (12-Month Base Study) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 1 (12-Month Base Study) | moved | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 1 (12-Month Base Study) | patient was unsure that they needed drug | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 1 (12-Month Base Study) | Protocol Violation | 1 | 0 | 3 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 1 (12-Month Base Study) | Withdrawal by Subject | 5 | 5 | 2 | 1 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 2 (12-Month Extension) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 6 | 1 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 2 (12-Month Extension) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 1 | 6 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 2 (12-Month Extension) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 2 (12-Month Extension) | Moved | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 2 (12-Month Extension) | Patient stopped taking medication | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 2 (12-Month Extension) | patient was out of windows | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 2 (12-Month Extension) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 2 (12-Month Extension) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 3 (12-Month Extension) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 3 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 3 (12-Month Extension) | cortisone therapy, upcoming surgery | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 3 (12-Month Extension) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 3 (12-Month Extension) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 3 (12-Month Extension) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Year 3 (12-Month Extension) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Years 4-5 (24-Month Extension) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 |
| Years 4-5 (24-Month Extension) | Discontinued for other reasons | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Years 4-5 (24-Month Extension) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 |
| Years 4-5 (24-Month Extension) | Participant moved | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Years 4-5 (24-Month Extension) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
| Years 6-10 (60-Month Extension) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 1 |
| Years 6-10 (60-Month Extension) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Years 6-10 (60-Month Extension) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Years 6-10 (60-Month Extension) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Years 6-10 (60-Month Extension) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Years 6-10 (60-Month Extension) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 6 | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo-Base | Odanacatib 3 Mg-Base | Odanacatib 10 Mg-Base | Odanacatib 25 Mg-Base | Odanacatib 50 Mg-Base | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 65.9 years STANDARD_DEVIATION 7.8 | 63.1 years STANDARD_DEVIATION 7.3 | 64.5 years STANDARD_DEVIATION 8 | 62.9 years STANDARD_DEVIATION 7.4 | 64.5 years STANDARD_DEVIATION 8.1 | 64.2 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 83 Participants | 82 Participants | 77 Participants | 79 Participants | 78 Participants | 399 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 68 / 83 | 66 / 82 | 67 / 77 | 67 / 79 | 66 / 78 | 17 / 19 | 13 / 22 | 16 / 18 | 14 / 17 | 13 / 18 | 15 / 17 | 15 / 19 | 17 / 21 | 14 / 18 | 15 / 20 | 64 / 73 | 24 / 27 | 33 / 41 | 25 / 28 | 31 / 34 | 23 / 23 | 30 / 32 |
| serious Total, serious adverse events | 8 / 83 | 12 / 82 | 10 / 77 | 9 / 79 | 14 / 78 | 2 / 19 | 2 / 22 | 3 / 18 | 2 / 17 | 1 / 18 | 1 / 17 | 2 / 19 | 3 / 21 | 2 / 18 | 1 / 20 | 16 / 73 | 2 / 27 | 8 / 41 | 8 / 28 | 14 / 34 | 6 / 23 | 12 / 32 |
Outcome results
Primary
Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Years 6-10 (up to 60 months)
Population: All participants who received at least 1 administration of the trial drug during treatment years 6-10.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-Base | Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months) | 1 Participants |
| Odanacatib 3 Mg-Base | Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months) | 2 Participants |
| Odanacatib 10 Mg-Base | Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months) | 0 Participants |
| Odanacatib 25 Mg-Base | Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months) | 1 Participants |
Primary
Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Years 6-10 (up to 60 months, up to 14 days after the last dose of study drug)
Population: All participants who received at least 1 administration of the trial drug during treatment years 6-10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-Base | Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months) | 27 Participants |
| Odanacatib 3 Mg-Base | Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months) | 34 Participants |
| Odanacatib 10 Mg-Base | Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months) | 23 Participants |
| Odanacatib 25 Mg-Base | Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months) | 32 Participants |
Primary
Percentage Change From Baseline in Lumbar Spine BMD at 120 Months
Percentage change from baseline in lumbar spine BMD at 120 Months.
Time frame: Baseline and Month 120
Population: This analysis was based on the FAS population, which included all randomized participants who took at least 1 dose of extension study drug and had the necessary extension data available for this endpoint. Missing data were not imputed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Lumbar Spine BMD at 120 Months | 16.92 Percentage Change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 120 Months | 14.56 Percentage Change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 120 Months | 17.18 Percentage Change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 120 Months | 7.71 Percentage Change |
Primary
Percentage Change From Baseline in Lumbar Spine BMD at 24 Months
Percentage change in lumbar spine BMD (relative to baseline) at 24 Months.
Time frame: Baseline and 24 months
Population: Analysis on lumbar spine BMD (g/cm2) at Month 24 used the Full-Analysis-Set Population with Last Observation Carried Forward from Month 18 to 24. No data were carried forward from the core to the extension period. Only patients who took at least one dose of extension medication were included. 17 patients were excluded from FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Lumbar Spine BMD at 24 Months | -0.19 Percentage Change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 24 Months | -1.03 Percentage Change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 24 Months | 3.20 Percentage Change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 24 Months | 4.26 Percentage Change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 24 Months | 5.48 Percentage Change |
Comparison: The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 24 months. The primary hypothesis states that odanacatib will increase lumbar spine BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [4.32, 7.02]ANCOVA
Comparison: The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 24 months. The primary hypothesis states that odanacatib will increase lumbar spine BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [3.15, 5.76]ANCOVA
Comparison: The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 24 months. The primary hypothesis states that odanacatib will increase lumbar spine BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [2.06, 4.73]ANCOVA
Comparison: The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 24 months. The primary hypothesis states that odanacatib will increase lumbar spine BMD compared to placebo over 24 months.p-value: 0.21895% CI: [-2.19, 0.51]ANCOVA
Primary
Percentage Change From Baseline in Lumbar Spine BMD at 36 Months
Percentage change in lumbar spine BMD (relative to baseline) at 36 months
Time frame: Baseline and 36 months
Population: This analysis was performed at Month 36 using the Per-protocol approach which includes patients who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from month 30 to 36.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | 0.42 Percent Change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | 2.95 Percent Change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | -1.57 Percent Change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | 4.41 Percent Change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | 2.03 Percent Change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | 6.11 Percent Change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | 0.32 Percent Change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | 7.45 Percent Change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | 1.39 Percent Change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Lumbar Spine BMD at 36 Months | 7.85 Percent Change |
Comparison: In postmenopausal women with osteoporosis assess the time course of resolution of effect on lumbar spine BMD during the 12 month extension following 24 months of treatment with odanacatib once weekly. The primary objective was to assess the resolution of effect, on lumbar spine BMD, for the participants who received odanacatib 50 mg for 3 years compared to those who received odanacatib 50 mg in the 2nd year and switched to placebo for the 3rd year extension.95% CI: [3.38, 9.53]
Primary
Percentage Change From Baseline in Lumbar Spine BMD at 60 Months
Percentage change from baseline in lumbar spine BMD at 60 months.
Time frame: Baseline and Month 60
Population: All participants who took at least one dose of base study medication and at least one dose of extension medication. Missing values were imputed using last observation-carried-forward principle.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Lumbar Spine BMD at 60 Months | -0.41 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Lumbar Spine BMD at 60 Months | 11.88 Percentage change |
Primary
Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months
Percentage change in lumbar spine BMD (relative to baseline) at 12 Months.
Time frame: Baseline and 12 months
Population: Analysis at Month 12 used Full-Analysis-Set Population of participants who took at least one dose of study medication and had necessary follow-up information, in their randomization treatment group, with last observation data carried forward. Seven patients had a baseline value, but no value at Month 12 for lumbar spine Bone Mineral Density.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | -0.13 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | -0.62 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | 1.50 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | 2.65 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | 3.37 Percentage change |
Comparison: The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 12 months. The primary hypothesis states that odanacatib will increase lumbar spine BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [2.54, 4.45]ANCOVA
Comparison: The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 12 months. The primary hypothesis states that odanacatib will increase lumbar spine BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [1.82, 3.73]ANCOVA
Comparison: The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 12 months. The primary hypothesis states that odanacatib will increase lumbar spine BMD compared to placebo over 12 months.p-value: 0.00395% CI: [0.68, 2.59]ANCOVA
Comparison: The primary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 12 months. The primary hypothesis states that odanacatib will increase lumbar spine BMD compared to placebo over 12 months.p-value: 0.34395% CI: [-1.44, 0.46]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase (s-BSAP)), at 12 Months
Time frame: Baseline and 12 months
Population: This analysis was a geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 12 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months | -2.77 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months | 42.08 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months | 8.95 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months | 2.66 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months | -18.35 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-BSAP) compared to placebo over 12 months.p-value: <=0.00195% CI: [-26.11, -5.04]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-BSAP) compared to placebo over 12 months.p-value: 0.64595% CI: [-6.02, 16.89]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-BSAP) compared to placebo over 12 months.95% CI: [-0.47, 23.92]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-BSAP) compared to placebo over 12 months.95% CI: [30.55, 59.16]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase (s-BSAP)) (relative to baseline) at 24 Months
Time frame: Baseline and 24 months
Population: Analysis used geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months | 3.38 Geometric LS Mean percent change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months | 40.17 Geometric LS Mean percent change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months | 2.99 Geometric LS Mean percent change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months | 10.62 Geometric LS Mean percent change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months | -13.62 Geometric LS Mean percent change |
Comparison: The secondary objective was to assess the effect of MK0822 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-BSAP) compared to placebo over 24 months.p-value: 0.00295% CI: [-28.84, -4.44]ANCOVA
Comparison: The secondary objective was to assess the effect of MK0822 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-BSAP) compared to placebo over 24 months.p-value: 0.85295% CI: [-5.73, 20.21]ANCOVA
Comparison: The secondary objective was to assess the effect of MK0822 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-BSAP) compared to placebo over 24 months.95% CI: [-13.69, 12.92]ANCOVA
Comparison: The secondary objective was to assess the effect of MK0822 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-BSAP) compared to placebo over 24 months.95% CI: [21.19, 52.38]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months
Geometric Mean Percentage change from baseline, in Biochemical Marker of Bone turnover (serum bone-specific alkaline phosphatase \[s-BSAP\]) at 36 Months
Time frame: Baseline and 36 months
Population: This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using a Per-Protocol approach where patients with important protocol deviations and major protocol violators were excluded from the analyses. The per-protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 7.73 Geometric Mean Percent Change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 10.86 Geometric Mean Percent Change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 14.26 Geometric Mean Percent Change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 9.13 Geometric Mean Percent Change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 12.95 Geometric Mean Percent Change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 8.49 Geometric Mean Percent Change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 33.74 Geometric Mean Percent Change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 11.12 Geometric Mean Percent Change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 1.30 Geometric Mean Percent Change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months | 17.90 Geometric Mean Percent Change |
95% CI: [-5.67, 38.85]
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (serum bone tartrate-resistant acid phosphatase isoform 5b \[TRAP 5-b\]) at 36 Months
Time frame: Baseline and 36 months
Population: This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 52.98 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 52.37 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 33.25 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 59.37 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 56.71 Percentage change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 82.94 Percentage change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 56.42 Percentage change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 77.90 Percentage change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 47.61 Percentage change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months | 96.70 Percentage change |
95% CI: [13.37, 84.83]
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen \[1-CTP\]) at 36 Months
Time frame: Baseline and 36 months
Population: This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 7.40 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 193.91 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 1.67 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 187.37 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 58.76 Percentage change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 188.50 Percentage change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 77.94 Percentage change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 231.93 Percentage change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 27.20 Percentage change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months | 236.64 Percentage change |
95% CI: [127.14, 291.73]
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months
Back-transformation (geometric mean) of the Least Squares (LS) Mean of the log-values Percentage change from baseline in Biochemical Marker of Bone turnover (serum C-telopeptides of Type 1 collagen (s-CTx)) at 12 Months.
Time frame: Baseline and 12 Months
Population: This analysis was a geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 12 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months | -0.58 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months | 19.12 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months | -22.24 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months | -36.15 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months | -56.91 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 12 months.p-value: <=0.00195% CI: [-75.86, -36.81]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 12 months.p-value: <=0.00195% CI: [-56.63, -14.51]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 12 months.p-value: 0.0895% CI: [-44.54, 1.23]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 12 months.95% CI: [-8.48, 47.88]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (serum C-telopeptides of Type 1 collagen (s-CTx)) (relative to baseline) at 24 Months
Time frame: Baseline and 24 months
Population: Analysis used geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The per-protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months | 32.77 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months | 54.94 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months | 8.79 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months | -6.52 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months | -30.57 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 24 months.p-value: <=0.00195% CI: [-88.32, -38.36]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 24 months.p-value: <=0.00195% CI: [-65.4, -13.18]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 24 months.p-value: 0.12495% CI: [-53.04, 5.09]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (s-CTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (s-CTx) over 24 months.95% CI: [-12.38, 56.73]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (s-CTx) at 36 Months
Time frame: Baseline and 36 months
Population: This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | -0.09 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | -41.30 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | -4.69 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | -44.62 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | 18.24 Percentage change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | -26.26 Percentage change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | 61.14 Percentage change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | -36.71 Percentage change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | 10.32 Percentage change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months | -23.93 Percentage change |
95% CI: [-78.7, 10.2]
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change in Biochemical Marker of Bone turnover (serum N-terminal propeptide of Type 1 collagen (s-P1NP) (relative to baseline) at 12 Months
Time frame: Baseline and 12 months
Population: This analysis was a geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 12 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months | 3.91 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months | 50.81 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months | 2.33 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months | 2.23 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months | -31.83 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-P1NP) compared to placebo over 12 months.p-value: <=0.00195% CI: [-52.14, -19.33]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-P1NP) compared to placebo over 12 months.p-value: 0.16195% CI: [-20.58, 17.23]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-P1NP) compared to placebo over 12 months.95% CI: [-20.99, 17.82]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-P1NP) compared to placebo over 12 months.95% CI: [22.35, 71.44]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months
Back-transformation (geometric mean) of the least squares mean of the log-values percentage change from baseline in biochemical marker of bone turnover (s-P1NP) (relative to baseline) at 24 months
Time frame: Baseline and 24 months
Population: Analysis used geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months | 1.29 Geometric LS Mean percent change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months | 50.52 Geometric LS Mean percent change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months | 9.07 Geometric LS Mean percent change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months | 14.60 Geometric LS Mean percent change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months | -20.20 Geometric LS Mean percent change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-P1NP) compared to placebo over 24 months.p-value: 0.01195% CI: [-39.55, -3.43]ANCOVA
Comparison: The secondary objective was to assess the effect of MK0822 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-P1NP) compared to placebo over 24 months.p-value: 0.61895% CI: [-7.1, 33.71]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-P1NP) compared to placebo over 24 months.95% CI: [-13.46, 29.01]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone formation (s-P1NP) compared to placebo over 24 months.95% CI: [23.86, 74.59]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (serum N-terminal propeptide of Type 1 collagen \[s-P1NP\]) at 36 months
Time frame: Baseline and 36 months
Population: This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | -20.79 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | -18.79 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | -13.11 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | -21.08 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | 8.58 Percentage change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | 12.44 Percentage change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | 22.57 Percentage change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | -8.14 Percentage change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | -0.77 Percentage change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months | -6.20 Percentage change |
95% CI: [-42.04, 31.18]
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months
Back-transformation (geometric mean) of the Least Squares (LS) Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary N-telopeptides of Type I collagen (u-NTx)) at 12 Months
Time frame: Baseline and 12 Months
Population: This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 12 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The per-protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months | -2.37 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months | 8.80 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months | -34.21 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months | -48.29 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months | -60.23 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 12 months.p-value: <=0.00195% CI: [-72.33, -43.38]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 12 months.p-value: <=0.00195% CI: [-60.93, -30.91]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 12 months.p-value: <=0.00195% CI: [-48.11, -15.58]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 12 months.p-value: 0.24995% CI: [-0.94, 43.24]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values percentage change from baseline in biochemical marker of bone turnover (u-NTx) (relative to baseline) at 24 Months
Time frame: Baseline and 24 months
Population: Analysis used a geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months | -4.62 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months | 12.89 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months | -40.57 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months | -38.30 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months | -51.83 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 24 months.p-value: <=0.00195% CI: [-64.51, -29.9]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 24 months.p-value: <=0.00195% CI: [-51.44, -15.91]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 24 months.p-value: <=0.00195% CI: [-54.15, -17.74]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-NTx) compared to placebo over 24 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-NTx) over 24 months.p-value: 0.10195% CI: [-6.78, 41.8]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover (u-NTx) at 36 Months
Time frame: Baseline and 36 months
Population: This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | -17.43 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | -55.12 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | -11.90 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | -57.17 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | -12.15 Percentage change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | -49.10 Percentage change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | 14.26 Percentage change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | -52.11 Percentage change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | 27.55 Percentage change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months | -50.51 Percentage change |
95% CI: [-119.2, -36.92]
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values percentage change from baseline in biochemical marker of bone turnover (urinary total deoxypyridinolines (u-DPyr)) (relative to baseline) at 12 Months
Time frame: Baseline and 12 months
Population: This analysis was a geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 12 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The per-protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months | -7.25 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months | 20.91 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months | -8.58 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months | -8.50 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months | -25.52 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-DPyr) over 12 months.p-value: 0.00495% CI: [-35.82, -0.74]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-DPyr) over 12 months.p-value: 0.34495% CI: [-19.9, 17.39]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-DPyr) over 12 months.95% CI: [-20.55, 17.89]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 12 months. The secondary hypothesis states that odanacatib will decrease biochemical indices of bone resorption (u-DPyr) over 12 months.95% CI: [5.84, 50.46]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months
Back-transformation (geometric mean) of the Least Squares Mean of the log-values Percentage change from baseline, in Biochemical Marker of Bone turnover (urinary total deoxypyridinolines (u-DPyr)) (relative to baseline) at 24 Months
Time frame: Baseline and 24 months
Population: Analysis used geometric mean percent change from baseline (back-transformation of a log-transformed fraction from baseline) at Month 24 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months | -5.78 Geometric LS Mean percent change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months | 15.96 Geometric LS Mean percent change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months | -7.57 Geometric LS Mean percent change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months | -14.30 Geometric LS Mean percent change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months | -22.49 Geometric LS Mean percent change |
Comparison: The secondary objective was to assess the effect of MK0822 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 24 months. The secondary hypothesis states that MK0822 will decrease biochemical indices of bone resorption (u-DPyr) over 24 months.p-value: 0.01595% CI: [-36.03, 2.61]ANCOVA
Comparison: The secondary objective was to assess the effect of MK0822 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 24 months. The secondary hypothesis states that MK0822 will decrease biochemical indices of bone resorption (u-DPyr) over 24 months.p-value: 0.24695% CI: [-27.31, 10.29]ANCOVA
Comparison: The secondary objective was to assess the effect of MK0822 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 24 months. The secondary hypothesis states that MK0822 will decrease biochemical indices of bone resorption (u-DPyr) over 24 months.95% CI: [-22.66, 19.08]ANCOVA
Comparison: The secondary objective was to assess the effect of MK0822 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on biochemical indices of bone resorption (u-DPyr) compared to placebo over 24 months. The secondary hypothesis states that MK0822 will decrease biochemical indices of bone resorption (u-DPyr) over 24 months.95% CI: [-1.32, 44.81]ANCOVA
Secondary
Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months
Percentage change from baseline in biochemical marker of bone turnover u-DPyr at 36 Months
Time frame: Baseline and 36 months
Population: This analysis was geometric mean percent change from baseline (which is a back-transformation of a log-transformed fraction from baseline) at Month 36 using a Per-Protocol approach. Participants with important protocol deviations and major protocol violators were excluded from the analyses. The Per-Protocol approach did not estimate missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | -18.69 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | -14.95 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | -7.82 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | -26.27 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | -4.69 Percentage change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | 0.43 Percentage change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | -9.16 Percentage change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | -16.41 Percentage change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | 22.41 Percentage change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months | -16.84 Percentage change |
95% CI: [-87.17, 8.68]
Secondary
Percentage Change From Baseline in Distal Forearm BMD at 12 Months
Percentage change in distal forearm BMD (relative to baseline) at 12 months
Time frame: Baseline and 12 Months
Population: This analysis was performed at Month 12 using Full-Analysis-Set Population with Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Distal Forearm BMD at 12 Months | -1.27 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 12 Months | -2.55 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 12 Months | -1.00 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 12 Months | -0.17 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 12 Months | -0.04 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on distal forearm BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase distal forearm BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [0.22, 2.24]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on distal forearm BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase distal forearm BMD compared to placebo over 12 months.p-value: 0.00595% CI: [0.09, 2.11]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on distal forearm BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase distal forearm BMD compared to placebo over 12 months.p-value: 0.6395% CI: [-0.74, 1.29]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on distal forearm BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase distal forearm BMD compared to placebo over 12 months.95% CI: [-2.28, -0.27]ANCOVA
Secondary
Percentage Change From Baseline in Distal Forearm BMD at 24 Months
Percentage change in distal forearm BMD (relative to baseline) at 24 Months
Time frame: Baseline and 24 months
Population: This analysis was performed at Month 24 using Full-Analysis-Set Population with Last Observation Carried Forward (from extension data). No data was carried forward from the core to the extension period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Distal Forearm BMD at 24 Months | -2.75 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 24 Months | -5.70 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 24 Months | -1.22 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 24 Months | -0.65 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 24 Months | 0.15 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Distal Forearm BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Distal Forearm BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [1.34, 4.46]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Distal Forearm BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Distal Forearm BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [0.59, 3.6]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Distal Forearm BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Distal Forearm BMD compared to placebo over 24 months.p-value: 0.09495% CI: [-0.01, 3.07]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Distal Forearm BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Distal Forearm BMD compared to placebo over 24 months.95% CI: [-4.5, -1.4]ANCOVA
Secondary
Percentage Change From Baseline in Distal Forearm BMD at 36 Months
Percentage change in distal forearm BMD (relative to baseline) at 36 Months
Time frame: Baseline and 36 months
Population: This analysis was performed at Month 36 using the Per-protocol approach which includes participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from month 30 to 36.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | -2.08 Percentage Change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | -4.04 Percentage Change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | -6.59 Percentage Change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | -6.34 Percentage Change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | -1.74 Percentage Change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | -3.74 Percentage Change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | -2.39 Percentage Change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | 0.53 Percentage Change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | -2.73 Percentage Change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Distal Forearm BMD at 36 Months | -0.26 Percentage Change |
95% CI: [-0.93, 5.88]
Secondary
Percentage Change From Baseline in Femoral Neck BMD at 12 Months
Percentage change in femoral neck BMD (relative to baseline) at 12 months
Time frame: Baseline and 12 months
Population: This analysis was performed at Month 12 using Full-Analysis-Set approach with Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Femoral Neck BMD at 12 Months | -0.13 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 12 Months | -0.32 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 12 Months | 0.74 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 12 Months | 1.76 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 12 Months | 2.53 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on femoral neck BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase femoral neck BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [1.71, 3.61]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on femoral neck BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase femoral neck BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [0.93, 2.84]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on femoral neck BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase femoral neck BMD compared to placebo over 12 months.p-value: 0.09595% CI: [-0.09, 1.82]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on femoral neck BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase femoral neck BMD compared to placebo over 12 months.95% CI: [-1.14, 0.75]ANCOVA
Secondary
Percentage Change From Baseline in Femoral Neck BMD at 24 Months
Percentage change in femoral neck Bone Mineral Density (relative to baseline) at 24 Months
Time frame: Baseline and 24 months
Population: This analysis was performed at Month 24 using Full-Analysis-Set Population with Last Observation Carried Forward (from extension data). No data was carried forward from the core to the extension period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Femoral Neck BMD at 24 Months | -0.85 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 24 Months | -1.25 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 24 Months | 1.97 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 24 Months | 2.73 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 24 Months | 3.84 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on femoral neck BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase femoral neck BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [3.25, 6.12]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on femoral neck BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase femoral neck BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [2.18, 4.97]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on femoral neck BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase femoral neck BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [1.39, 4.25]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on femoral neck BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase femoral neck BMD compared to placebo over 24 months.p-value: 0.58595% CI: [-1.85, 1.04]ANCOVA
Secondary
Percentage Change From Baseline in Femoral Neck BMD at 36 Months
Percentage change in femoral neck BMD (relative to baseline) at 36 Months
Time frame: Baseline and 36 months
Population: This analysis was performed at Month 36 using the Per-Protocol approach which includes participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from month 30 to 36.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | -0.52 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | 1.03 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | -1.04 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | 2.26 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | -0.14 Percentage change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | 5.06 Percentage change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | 0.80 Percentage change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | 7.23 Percentage change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | 2.26 Percentage change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Femoral Neck BMD at 36 Months | 4.97 Percentage change |
95% CI: [-0.16, 5.57]
Secondary
Percentage Change From Baseline in Total Body BMD at 12 Months
Percentage change in total body BMD (relative to baseline) at 12 months
Time frame: Baseline and 12 Months
Population: This analysis was performed at Month 12 using Full-Analysis-Set Population with Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Total Body BMD at 12 Months | -0.42 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Total Body BMD at 12 Months | -1.89 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Total Body BMD at 12 Months | -1.06 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Total Body BMD at 12 Months | -0.51 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Total Body BMD at 12 Months | -0.13 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total body BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase total body BMD compared to placebo over 12 months.p-value: 0.11295% CI: [-0.77, 1.35]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total body BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase total body BMD compared to placebo over 12 months.95% CI: [-1.13, 0.95]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total body BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase total body BMD compared to placebo over 12 months.95% CI: [-1.69, 0.42]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total body BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase total body BMD compared to placebo over 12 months.95% CI: [-2.53, -0.42]ANCOVA
Secondary
Percentage Change From Baseline in Total Body BMD at 24 Months
Percentage change in total body BMD (relative to baseline) at 24 Months
Time frame: Baseline and 24 months
Population: This analysis was performed at Month 24 using Full-Analysis-Set Population with Last Observation Carried Forward. No data was carried forward from the core to the extension period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Total Body BMD at 24 Months | -1.54 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Total Body BMD at 24 Months | -2.70 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Total Body BMD at 24 Months | -1.35 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Total Body BMD at 24 Months | -0.43 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Total Body BMD at 24 Months | 0.19 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Total Body BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Total Body BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [0.46, 3.01]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Total Body BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Total Body BMD compared to placebo over 24 months.p-value: 0.02895% CI: [-0.12, 2.34]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Total Body BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Total Body BMD compared to placebo over 24 months.p-value: 0.80495% CI: [-1.1, 1.49]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on Total Body BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase Total Body BMD compared to placebo over 24 months.95% CI: [-2.46, 0.15]ANCOVA
Secondary
Percentage Change From Baseline in Total Body BMD at 36 Months
Percentage change from baseline in total body BMD (relative to baseline) at 36 Months
Time frame: Baseline and 36 months
Population: This analysis was performed at Month 36 using the Per-Protocol approach which includes participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from month 30 to 36.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Total Body BMD at 36 Months | 0.13 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Total Body BMD at 36 Months | -2.20 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Total Body BMD at 36 Months | -3.63 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Total Body BMD at 36 Months | 0.28 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Total Body BMD at 36 Months | -2.28 Percentage change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Total Body BMD at 36 Months | -1.22 Percentage change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Total Body BMD at 36 Months | -0.85 Percentage change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Total Body BMD at 36 Months | 0.56 Percentage change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Total Body BMD at 36 Months | -1.84 Percentage change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Total Body BMD at 36 Months | -0.38 Percentage change |
95% CI: [-1.54, 4.46]
Secondary
Percentage Change From Baseline in Total Hip BMD at 12 Months
Percentage change in total hip BMD (relative to baseline) at 12 months
Time frame: Baseline and 12 months
Population: This analysis was performed at Month 12 using Full-Analysis-Set approach with Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Total Hip BMD at 12 Months | -0.61 Percentage Change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Total Hip BMD at 12 Months | -1.36 Percentage Change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Total Hip BMD at 12 Months | 1.05 Percentage Change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Total Hip BMD at 12 Months | 1.45 Percentage Change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Total Hip BMD at 12 Months | 1.87 Percentage Change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total hip BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase total hip BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [1.62, 3.35]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total hip BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase total hip BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [1.2, 2.93]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total hip BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase total hip BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [0.8, 2.53]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total hip BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase total hip BMD compared to placebo over 12 months.p-value: 0.13595% CI: [-1.61, 0.11]ANCOVA
Secondary
Percentage Change From Baseline in Total Hip BMD at 36 Months
Percentage change in total hip BMD (relative to baseline) at 36 months
Time frame: Baseline and 36 months
Population: This analysis was performed at Month 36 using the Per-Protocol approach which includes participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from month 30 to 36.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Total Hip BMD at 36 Months | -0.77 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Total Hip BMD at 36 Months | 1.16 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Total Hip BMD at 36 Months | -0.63 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Total Hip BMD at 36 Months | 2.75 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Total Hip BMD at 36 Months | 0.96 Percentage change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Total Hip BMD at 36 Months | 4.61 Percentage change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Total Hip BMD at 36 Months | 1.64 Percentage change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Total Hip BMD at 36 Months | 5.70 Percentage change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Total Hip BMD at 36 Months | -0.48 Percentage change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Total Hip BMD at 36 Months | 5.83 Percentage change |
95% CI: [3.44, 9.17]
Secondary
Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months
Percentage change in total hip Bone Mineral Density (relative to baseline) at 24 Months
Time frame: Baseline and 24 months
Population: This analysis was performed at Month 24 using Full-Analysis-Set Population with Last Observation Carried Forward (from extension data). No data was carried forward from the core to the extension period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months | -0.93 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months | -1.44 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months | 1.82 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months | 2.55 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months | 3.16 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total hip BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase total hip BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [2.77, 5.42]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total hip BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase total hip BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [2.2, 4.77]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total hip BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase total hip BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [1.43, 4.07]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on total hip BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase total hip BMD compared to placebo over 24 months.p-value: 0.53695% CI: [-1.84, 0.83]ANCOVA
Secondary
Percentage Change From Baseline in Trochanter BMD at 12 Months
Percentage change in trochanter BMD (relative to baseline) at 12 months
Time frame: Baseline and 12 Months
Population: This analysis was performed at Month 12 using Full-Analysis-Set approach with Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Trochanter BMD at 12 Months | -0.73 Percentage change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 12 Months | -1.02 Percentage change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 12 Months | 1.65 Percentage change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 12 Months | 1.91 Percentage change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 12 Months | 2.21 Percentage change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on trochanter BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase trochanter BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [1.64, 4.24]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on trochanter BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase trochanter BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [1.35, 3.94]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on trochanter BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase trochanter BMD compared to placebo over 12 months.p-value: <=0.00195% CI: [1.08, 3.69]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on trochanter BMD compared to placebo over 12 months. The secondary hypothesis states that odanacatib will increase trochanter BMD compared to placebo over 12 months.p-value: 0.73195% CI: [-1.58, 1]ANCOVA
Secondary
Percentage Change From Baseline in Trochanter BMD at 24 Months
Percentage change from baseline in trochanter BMD (relative to baseline) at 24 Months
Time frame: Baseline and 24 months
Population: This analysis was performed at Month 24 using Full-Analysis-Set Population with Last Observation Carried Forward (from extension data). No data was carried forward from the core to the extension period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Trochanter BMD at 24 Months | -0.81 Percentage Change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 24 Months | -0.85 Percentage Change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 24 Months | 3.61 Percentage Change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 24 Months | 3.75 Percentage Change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 24 Months | 4.28 Percentage Change |
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on trochanter BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase trochanter BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [3.18, 7.01]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on trochanter BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase trochanter BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [2.7, 6.42]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on trochanter BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase trochanter BMD compared to placebo over 24 months.p-value: <=0.00195% CI: [2.52, 6.33]ANCOVA
Comparison: The secondary objective was to assess the effect of odanacatib 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on trochanter BMD compared to placebo over 24 months. The secondary hypothesis states that odanacatib will increase trochanter BMD compared to placebo over 24 months.p-value: 0.98195% CI: [-1.97, 1.89]ANCOVA
Secondary
Percentage Change From Baseline in Trochanter BMD at 36 Months
Percentage change in trochanter BMD (relative to baseline) at 36 months
Time frame: Baseline and 36 months
Population: This analysis was performed at Month 36 using the Per-Protocol approach which includes participants who took at least one dose of extension study medication and had the necessary follow-up information. Missing values were not imputed. No data were carried forward from month 30 to 36.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo-Base | Percentage Change From Baseline in Trochanter BMD at 36 Months | -0.46 Percentage Change |
| Odanacatib 3 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 36 Months | 2.32 Percentage Change |
| Odanacatib 10 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 36 Months | -1.04 Percentage Change |
| Odanacatib 25 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 36 Months | 4.53 Percentage Change |
| Odanacatib 50 Mg-Base | Percentage Change From Baseline in Trochanter BMD at 36 Months | 0.66 Percentage Change |
| Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Trochanter BMD at 36 Months | 8.21 Percentage Change |
| Odanacatib 25 mg / Placebo-Ext 2 | Percentage Change From Baseline in Trochanter BMD at 36 Months | 1.14 Percentage Change |
| Odanacatib 25 mg / 50 Mg-Ext 2 | Percentage Change From Baseline in Trochanter BMD at 36 Months | 7.97 Percentage Change |
| Odanacatib 50 mg / Placebo-Ext 2 | Percentage Change From Baseline in Trochanter BMD at 36 Months | -0.69 Percentage Change |
| Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 | Percentage Change From Baseline in Trochanter BMD at 36 Months | 7.44 Percentage Change |
95% CI: [3.8, 12.46]