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

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00112437
Collaborator
(none)
399
Enrollment
5
Arms
126.9
Actual Duration (Months)

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
399 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of MK-0822 (Cathepsin K Inhibitor) in the Treatment of Postmenopausal Women With Osteoporosis
Actual Study Start Date :
Jun 24, 2005
Actual Primary Completion Date :
Dec 26, 2007
Actual Study Completion Date :
Jan 20, 2016

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Dietary Supplement: Vitamin D3
Vitamin D3, two 2800 IU weekly throughout the study

Dietary Supplement: Calcium Carbonate
Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.

Drug: Placebo
Placebo to Odanacatib 3 mg, 10 mg, 25 mg, or 50 once weekly for 24 months
Experimental: Odanacatib 3 mg

Drug: Odanacatib
Odanacatib 3 mg, once weekly for 24 months
Other Names:
  • MK-0822

    • Dietary Supplement: Vitamin D3
    Vitamin D3, two 2800 IU weekly throughout the study

    Dietary Supplement: Calcium Carbonate
    Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
    Experimental: Odanacatib 10 mg

    Drug: Odanacatib
    Odanacatib 10 mg, once weekly for 24 months
    Other Names:
  • MK-0822

    • Dietary Supplement: Vitamin D3
    Vitamin D3, two 2800 IU weekly throughout the study

    Dietary Supplement: Calcium Carbonate
    Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
    Experimental: Odanacatib 25 mg

    Drug: Odanacatib
    Odanacatib 25 mg, once weekly for 24 months
    Other Names:
  • MK-0822

    • Dietary Supplement: Vitamin D3
    Vitamin D3, two 2800 IU weekly throughout the study

    Dietary Supplement: Calcium Carbonate
    Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.
    Experimental: Odanacatib 50 mg

    Drug: Odanacatib
    Odanacatib 50 mg, once weekly for 24 months
    Other Names:
  • MK-0822

    • Dietary Supplement: Vitamin D3
    Vitamin D3, two 2800 IU weekly throughout the study

    Dietary Supplement: Calcium Carbonate
    Participants who have a calcium intake less than 1000 mg/day will receive daily calcium supplements providing 500 mg of elemental calcium.

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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

    4. 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.

    5. 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.

    6. 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.

    7. 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 Outcome Measures

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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

    6. 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

    7. 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.

    8. 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

    9. 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

    10. 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

    11. 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

    12. 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

    13. 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

    14. 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

    15. 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

    16. 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

    17. 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

    18. 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

    19. 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

    20. 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

    21. 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

    22. 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

    23. 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

    24. 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

    25. 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

    26. 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

    27. 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

    28. 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

    29. 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

    30. 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

    31. 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

    32. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    45 Years to 85 Years
    Sexes Eligible for Study:
    Female
    Accepts 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 exclusion criteria apply to each bone active drug. For example, any prior use of intravenous (IV) bisphosphonates is not permitted. By contrast, prior use of hormone replacement for several years is permitted if it has not occurred within the past 6 months. Please ask the study doctor for details)

    • Significant clinical or laboratory abnormalities at the screening visit for the study that, in the opinion of the investigator, could complicate interpretation of the study results or pose additional risk to the patient (for example, patients who are non-ambulatory should be excluded for this reason)

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Monitor, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00112437
    Other Study ID Numbers:
    • 0822-004
    • 2005_023
    First Posted:
    Jun 3, 2005
    Last Update Posted:
    Jan 24, 2018
    Last Verified:
    Dec 1, 2017
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Osteoporosis
    Vitamin D
    Cholecalciferol
    Calcium Carbonate
    Calcium

    Study Results

    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 Detail 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).
    Arm/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1 Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / Placebo-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2 Placebo Once Weekly-Ext 3 Odanacatib 50 mg Once Weekly-Ext 3 Group A: Odanacatib 50 mg Once Weekly-Ext 4 Group B: Odanacatib 50 mg Once Weekly-Ext 4 Group C: Odanacatib 50 mg Once Weekly-Ext 4 Group D: Odanacatib 50 mg Once Weekly-Ext 4
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 24-month extension (Years 4-5), participants in this treatment group received one placebo tablet once a week. During this 24-month extension (Years 4-5), participants in this treatment group received one odanacatib 50 mg tablet once a week. During this 60-month extension (Years 6-10), participants in this treatment group received one odanacatib 50 mg tablet one a week. Group A consisted of a combination of participants who were treated with odanacatib 25 mg for 2 years,then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 50 mg for 10 years. During this 60-month extension (Years 6-10), participants in this treatment group received one odanacatib 50 mg tablet one a week. Group B consisted of a combination participants who were treated with placebo for 2 years, then odanacatib 50 mg for 8 years; participants who were treated with odanacatib 3 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 10 mg for 2 years, then odanacatib 50 mg for 8 years. During this 60-month extension (Years 6-10), participants in this treatment group received one odanacatib 50 mg tablet one a week. Group C consisted of a combination of participants who were treated with placebo for 3 years, then odanacatib 50 mg for 7 years; and participants who were treated with odanacatib 3 mg for 2 years, then placebo for 1 year, then odanacatib 50 mg for 7 years. During this 60-month extension (Years 6-10), participants in this treatment group received one odanacatib 50 mg tablet once a week. Group D consists of a combination of participants who were treated with odanacatib 10 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; participants who were treated with odanacatib 25 mg for 5 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; and participants who were treated with odanacatib 50 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years.
    Period Title: Year 1 (12-Month Base Study)
    STARTED 83 82 77 79 78 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    COMPLETED 68 64 65 71 66 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 15 18 12 8 12 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    Period Title: Year 1 (12-Month Base Study)
    STARTED 0 0 0 0 0 63 62 63 69 63 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    COMPLETED 0 0 0 0 0 60 53 55 62 50 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 0 0 0 0 0 3 9 8 7 13 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    Period Title: Year 1 (12-Month Base Study)
    STARTED 0 0 0 0 0 0 0 0 0 0 19 22 18 17 18 17 19 21 18 20 0 0 0 0 0 0
    COMPLETED 0 0 0 0 0 0 0 0 0 0 17 17 18 16 17 13 16 20 16 19 0 0 0 0 0 0
    NOT COMPLETED 0 0 0 0 0 0 0 0 0 0 2 5 0 1 1 4 3 1 2 1 0 0 0 0 0 0
    Period Title: Year 1 (12-Month Base Study)
    STARTED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 41 100 0 0 0 0
    COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 37 92 0 0 0 0
    NOT COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 8 0 0 0 0
    Period Title: Year 1 (12-Month Base Study)
    STARTED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 28 34 23 32
    COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 23 22 22 27
    NOT COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 12 1 5

    Baseline Characteristics

    Arm/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base Total
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week Total of all reporting groups
    Overall Participants 83 82 77 79 78 399
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.9
    (7.8)
    63.1
    (7.3)
    64.5
    (8.0)
    62.9
    (7.4)
    64.5
    (8.1)
    64.2
    (7.8)
    Sex: Female, Male (Count of Participants)
    Female
    83
    100%
    82
    100%
    77
    100%
    79
    100%
    78
    100%
    399
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months
    Description Percentage change in lumbar spine BMD (relative to baseline) at 12 Months.
    Time Frame Baseline and 12 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 81 79 77 78 77
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.13
    -0.62
    1.50
    2.65
    3.37
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 3.50
    Confidence Interval (2-Sided) 95%
    2.54 to 4.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 2.78
    Confidence Interval (2-Sided) 95%
    1.82 to 3.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 1.63
    Confidence Interval (2-Sided) 95%
    0.68 to 2.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.343
    Comments Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -0.49
    Confidence Interval (2-Sided) 95%
    -1.44 to 0.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Percentage Change From Baseline in Lumbar Spine BMD at 24 Months
    Description Percentage change in lumbar spine BMD (relative to baseline) at 24 Months.
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 62 58 60 65 58
    Least Squares Mean (95% Confidence Interval) [Percentage Change]
    -0.19
    -1.03
    3.20
    4.26
    5.48
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 5.67
    Confidence Interval (2-Sided) 95%
    4.32 to 7.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 4.45
    Confidence Interval (2-Sided) 95%
    3.15 to 5.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 3.39
    Confidence Interval (2-Sided) 95%
    2.06 to 4.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.218
    Comments Significance for the primary endpoint was achieved through stepdown trend-test, the highest dose group was removed and the test was repeated until lack of significance was observed.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -0.84
    Confidence Interval () 95%
    -2.19 to 0.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage Change From Baseline in Total Hip BMD at 12 Months
    Description Percentage change in total hip BMD (relative to baseline) at 12 months
    Time Frame Baseline and 12 months

    Outcome Measure Data

    Analysis Population Description
    This analysis was performed at Month 12 using Full-Analysis-Set approach with Last Observation Carried Forward.
    Arm/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 81 79 77 78 77
    Least Squares Mean (95% Confidence Interval) [Percentage Change]
    -0.61
    -1.36
    1.05
    1.45
    1.87
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 2.49
    Confidence Interval (2-Sided) 95%
    1.62 to 3.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 2.06
    Confidence Interval (2-Sided) 95%
    1.20 to 2.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 1.67
    Confidence Interval (2-Sided) 95%
    0.80 to 2.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.135
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -0.75
    Confidence Interval (2-Sided) 95%
    -1.61 to 0.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage Change From Baseline in Femoral Neck BMD at 12 Months
    Description Percentage change in femoral neck BMD (relative to baseline) at 12 months
    Time Frame Baseline and 12 months

    Outcome Measure Data

    Analysis Population Description
    This analysis was performed at Month 12 using Full-Analysis-Set approach with Last Observation Carried Forward.
    Arm/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 81 79 77 78 77
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.13
    -0.32
    0.74
    1.76
    2.53
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 2.66
    Confidence Interval (2-Sided) 95%
    1.71 to 3.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 1.89
    Confidence Interval (2-Sided) 95%
    0.93 to 2.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.095
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 0.87
    Confidence Interval (2-Sided) 95%
    -0.09 to 1.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -1.14 to 0.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Percentage Change From Baseline in Trochanter BMD at 12 Months
    Description Percentage change in trochanter BMD (relative to baseline) at 12 months
    Time Frame Baseline and 12 Months

    Outcome Measure Data

    Analysis Population Description
    This analysis was performed at Month 12 using Full-Analysis-Set approach with Last Observation Carried Forward.
    Arm/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 81 79 77 78 77
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.73
    -1.02
    1.65
    1.91
    2.21
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 2.94
    Confidence Interval (2-Sided) 95%
    1.64 to 4.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 2.65
    Confidence Interval (2-Sided) 95%
    1.35 to 3.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 2.38
    Confidence Interval (2-Sided) 95%
    1.08 to 3.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.731
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -1.58 to 1.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Percentage Change From Baseline in Total Body BMD at 12 Months
    Description Percentage change in total body BMD (relative to baseline) at 12 months
    Time Frame Baseline and 12 Months

    Outcome Measure Data

    Analysis Population Description
    This analysis was performed at Month 12 using Full-Analysis-Set Population with Last Observation Carried Forward.
    Arm/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 72 71 70 75 70
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.42
    -1.89
    -1.06
    -0.51
    -0.13
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.112
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 0.29
    Confidence Interval (2-Sided) 95%
    -0.77 to 1.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -0.09
    Confidence Interval (2-Sided) 95%
    -1.13 to 0.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -0.63
    Confidence Interval (2-Sided) 95%
    -1.69 to 0.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -1.47
    Confidence Interval (2-Sided) 95%
    -2.53 to -0.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percentage Change From Baseline in Distal Forearm BMD at 12 Months
    Description Percentage change in distal forearm BMD (relative to baseline) at 12 months
    Time Frame Baseline and 12 Months

    Outcome Measure Data

    Analysis Population Description
    This analysis was performed at Month 12 using Full-Analysis-Set Population with Last Observation Carried Forward
    Arm/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 81 79 77 78 77
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -1.27
    -2.55
    -1.00
    -0.17
    -0.04
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 1.23
    Confidence Interval (2-Sided) 95%
    0.22 to 2.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 1.10
    Confidence Interval (2-Sided) 95%
    0.09 to 2.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.630
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 0.27
    Confidence Interval (2-Sided) 95%
    -0.74 to 1.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -1.27
    Confidence Interval (2-Sided) 95%
    -2.28 to -0.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 62 57 56 63 56
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -2.37
    8.80
    -34.21
    -48.29
    -60.23
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -57.86
    Confidence Interval (2-Sided) 95%
    -72.33 to -43.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fractions from baseline)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -45.92
    Confidence Interval (2-Sided) 95%
    -60.93 to -30.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fractions from baseline)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -31.84
    Confidence Interval (2-Sided) 95%
    -48.11 to -15.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fractions from baseline)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.249
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 11.17
    Confidence Interval (2-Sided) 95%
    -0.94 to 43.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fractions from baseline)
    9. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 62 57 56 62 55
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.58
    19.12
    -22.24
    -36.15
    -56.91
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -56.33
    Confidence Interval () 95%
    -75.86 to -36.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation from difference in log-fraction)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -35.57
    Confidence Interval () 95%
    -56.63 to -14.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation from difference in log-fraction)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.080
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -21.66
    Confidence Interval () 95%
    -44.54 to 1.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation from difference in log-fraction)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 19.70
    Confidence Interval (2-Sided) 95%
    -8.48 to 47.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation from difference in log-fraction)
    10. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 60 57 55 63 55
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -7.25
    20.91
    -8.58
    -8.50
    -25.52
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -18.28
    Confidence Interval (2-Sided) 95%
    -35.82 to -0.74
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fractions from baseline)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.344
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -1.26
    Confidence Interval (2-Sided) 95%
    -19.90 to 17.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fractions from baseline)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -1.33
    Confidence Interval (2-Sided) 95%
    -20.55 to 17.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fractions from baseline)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 28.15
    Confidence Interval (2-Sided) 95%
    5.84 to 50.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fractions from baseline)
    11. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 62 58 57 64 58
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -2.77
    42.08
    8.95
    2.66
    -18.35
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -15.57
    Confidence Interval (2-Sided) 95%
    -26.11 to -5.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation from difference in log-fraction from baseline)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.645
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 5.43
    Confidence Interval (2-Sided) 95%
    -6.02 to 16.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation from difference in log-fraction from baseline)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 11.73
    Confidence Interval (2-Sided) 95%
    -0.47 to 23.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation from difference in log-fraction from baseline)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 44.85
    Confidence Interval (2-Sided) 95%
    30.55 to 59.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation from difference in log-fraction from baseline)
    12. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Base Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 62 57 57 63 58
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    3.91
    50.81
    2.33
    2.23
    -31.83
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -35.74
    Confidence Interval (2-Sided) 95%
    -52.14 to -19.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fraction from baseline)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.161
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -1.68
    Confidence Interval (2-Sided) 95%
    -20.58 to 17.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fraction from baseline)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -1.58
    Confidence Interval (2-Sided) 95%
    -20.99 to 17.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fraction from baseline)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 46.90
    Confidence Interval (2-Sided) 95%
    22.35 to 71.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fraction from baseline)
    13. Secondary Outcome
    Title Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months
    Description Percentage change in total hip Bone Mineral Density (relative to baseline) at 24 Months
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 61 57 59 65 58
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.93
    -1.44
    1.82
    2.55
    3.16
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 4.10
    Confidence Interval (2-Sided) 95%
    2.77 to 5.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 3.48
    Confidence Interval (2-Sided) 95%
    2.20 to 4.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 2.75
    Confidence Interval (2-Sided) 95%
    1.43 to 4.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.536
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -0.51
    Confidence Interval (2-Sided) 95%
    -1.84 to 0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Percentage Change From Baseline in Femoral Neck BMD at 24 Months
    Description Percentage change in femoral neck Bone Mineral Density (relative to baseline) at 24 Months
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 61 57 59 65 58
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.85
    -1.25
    1.97
    2.73
    3.84
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 4.69
    Confidence Interval (2-Sided) 95%
    3.25 to 6.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 3.57
    Confidence Interval (2-Sided) 95%
    2.18 to 4.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 2.82
    Confidence Interval (2-Sided) 95%
    1.39 to 4.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.585
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -0.41
    Confidence Interval (2-Sided) 95%
    -1.85 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Percentage Change From Baseline in Trochanter BMD at 24 Months
    Description Percentage change from baseline in trochanter BMD (relative to baseline) at 24 Months
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 61 57 59 65 58
    Least Squares Mean (95% Confidence Interval) [Percentage Change]
    -0.81
    -0.85
    3.61
    3.75
    4.28
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 5.09
    Confidence Interval (2-Sided) 95%
    3.18 to 7.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 4.56
    Confidence Interval (2-Sided) 95%
    2.70 to 6.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 4.43
    Confidence Interval (2-Sided) 95%
    2.52 to 6.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.981
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -0.04
    Confidence Interval (2-Sided) 95%
    -1.97 to 1.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title Percentage Change From Baseline in Total Body BMD at 24 Months
    Description Percentage change in total body BMD (relative to baseline) at 24 Months
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 56 47 48 58 51
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -1.54
    -2.70
    -1.35
    -0.43
    0.19
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value 1.73
    Confidence Interval () 95%
    0.46 to 3.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.028
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value 1.11
    Confidence Interval () 95%
    -0.12 to 2.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.804
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value 0.20
    Confidence Interval () 95%
    -1.10 to 1.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value -1.15
    Confidence Interval (2-Sided) 95%
    -2.46 to 0.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    17. Secondary Outcome
    Title Percentage Change From Baseline in Distal Forearm BMD at 24 Months
    Description Percentage change in distal forearm BMD (relative to baseline) at 24 Months
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 61 58 60 65 57
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -2.75
    -5.70
    -1.22
    -0.65
    0.15
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value 2.90
    Confidence Interval (2-Sided) 95%
    1.34 to 4.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value 2.09
    Confidence Interval () 95%
    0.59 to 3.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.094
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor in the model, with 5% significance.
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value 1.53
    Confidence Interval () 95%
    -0.01 to 3.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value -2.95
    Confidence Interval () 95%
    -4.50 to -1.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    18. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Base Odanacatib 3 Mg-Base Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Base Odanacatib 50 Mg-Base
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 56 45 41 51 38
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -4.62
    12.89
    -40.57
    -38.30
    -51.83
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -47.21
    Confidence Interval () 95%
    -64.51 to -29.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -33.67
    Confidence Interval () 95%
    -51.44 to -15.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -35.94
    Confidence Interval () 95%
    -54.15 to -17.74
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.101
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handle by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 17.51
    Confidence Interval (2-Sided) 95%
    -6.78 to 41.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline)
    19. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 56 45 42 52 39
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    32.77
    54.94
    8.79
    -6.52
    -30.57
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -63.34
    Confidence Interval () 95%
    -88.32 to -38.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -39.29
    Confidence Interval (2-Sided) 95%
    -65.40 to -13.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fraction from baseline).
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.124
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure.
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -23.98
    Confidence Interval (2-Sided) 95%
    -53.04 to 5.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fraction from baseline).
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 22.18
    Confidence Interval (2-Sided) 95%
    -12.38 to 56.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fraction from baseline).
    20. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 56 45 40 51 38
    Least Squares Mean (95% Confidence Interval) [Geometric LS Mean percent change]
    -5.78
    15.96
    -7.57
    -14.30
    -22.49
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -16.71
    Confidence Interval () 95%
    -36.03 to 2.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.246
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -8.51
    Confidence Interval () 95%
    -27.31 to 10.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline).
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -1.79
    Confidence Interval () 95%
    -22.66 to 19.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline).
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 21.74
    Confidence Interval () 95%
    -1.32 to 44.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline).
    21. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 57 47 42 53 42
    Least Squares Mean (95% Confidence Interval) [Geometric LS Mean percent change]
    3.38
    40.17
    2.99
    10.62
    -13.62
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -16.64
    Confidence Interval () 95%
    -28.84 to -4.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fractions from baseline)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.852
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 7.24
    Confidence Interval () 95%
    -5.73 to 20.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fractions from baseline)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -0.39
    Confidence Interval () 95%
    -13.69 to 12.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fractions from baseline)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 36.79
    Confidence Interval () 95%
    21.19 to 52.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fractions from baseline)
    22. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo-Ext 1 Odanacatib 3 Mg-Ext 1 Odanacatib 10 Mg-Ext 1 Odanacatib 25 Mg-Ext 1 Odanacatib 50 Mg-Ext 1
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 57 47 42 53 42
    Least Squares Mean (95% Confidence Interval) [Geometric LS Mean percent change]
    1.29
    50.52
    9.07
    14.60
    -20.20
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 50 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value -21.49
    Confidence Interval (2-Sided) 95%
    -39.55 to -3.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fraction from baseline)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 25 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.618
    Comments Significance for secondary endpoints was only declared if there was also significance for the primary endpoint. Multiplicity was addressed through a stepdown trend-test approach. Multiplicity for multiple endpoints was handled by a Hochberg procedure
    Method ANCOVA
    Comments Stepwise linear trend test on ANCOVA model of log-fraction with treatment (scales 0, 1, 2, 3, 4) as covariate and center as factor, 5% significance.
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value 13.31
    Confidence Interval () 95%
    -7.10 to 33.71
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least square means (back-transformation of difference in log-fraction from baseline)
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 10 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least square means
    Estimated Value 7.77
    Confidence Interval (2-Sided) 95%
    -13.46 to 29.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Squares Means (back-transformation of difference in log-fraction from baseline)
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo-Base, Odanacatib 3 Mg-Base
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 49.23
    Confidence Interval (2-Sided) 95%
    23.86 to 74.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments Difference in Least Square Means (back-transformation of difference in log-fraction from baseline)
    23. Primary Outcome
    Title Percentage Change From Baseline in Lumbar Spine BMD at 36 Months
    Description Percentage change in lumbar spine BMD (relative to baseline) at 36 months
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / Placebo-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 16 17 13 12 10 12 18 15 17
    Least Squares Mean (95% Confidence Interval) [Percent Change]
    0.42
    2.95
    -1.57
    4.41
    2.03
    6.11
    0.32
    7.45
    1.39
    7.85
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 6.45
    Confidence Interval (2-Sided) 95%
    3.38 to 9.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    24. Secondary Outcome
    Title Percentage Change From Baseline in Total Hip BMD at 36 Months
    Description Percentage change in total hip BMD (relative to baseline) at 36 months
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 16 17 12 11 9 12 19 15 17
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.77
    1.16
    -0.63
    2.75
    0.96
    4.61
    1.64
    5.70
    -0.48
    5.83
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 6.31
    Confidence Interval (2-Sided) 95%
    3.44 to 9.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    25. Secondary Outcome
    Title Percentage Change From Baseline in Femoral Neck BMD at 36 Months
    Description Percentage change in femoral neck BMD (relative to baseline) at 36 Months
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 16 17 12 11 9 12 19 15 17
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.52
    1.03
    -1.04
    2.26
    -0.14
    5.06
    0.80
    7.23
    2.26
    4.97
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 2.71
    Confidence Interval (2-Sided) 95%
    -0.16 to 5.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    26. Secondary Outcome
    Title Percentage Change From Baseline in Trochanter BMD at 36 Months
    Description Percentage change in trochanter BMD (relative to baseline) at 36 months
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 16 17 12 11 9 12 19 15 17
    Least Squares Mean (95% Confidence Interval) [Percentage Change]
    -0.46
    2.32
    -1.04
    4.53
    0.66
    8.21
    1.14
    7.97
    -0.69
    7.44
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 8.13
    Confidence Interval (2-Sided) 95%
    3.80 to 12.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    27. Secondary Outcome
    Title Percentage Change From Baseline in Total Body BMD at 36 Months
    Description Percentage change from baseline in total body BMD (relative to baseline) at 36 Months
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 14 16 13 12 9 12 18 15 17
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    0.13
    -2.20
    -3.63
    0.28
    -2.28
    -1.22
    -0.85
    0.56
    -1.84
    -0.38
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 1.46
    Confidence Interval (2-Sided) 95%
    -1.54 to 4.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    28. Secondary Outcome
    Title Percentage Change From Baseline in Distal Forearm BMD at 36 Months
    Description Percentage change in distal forearm BMD (relative to baseline) at 36 Months
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 15 16 13 12 10 12 18 14 17
    Least Squares Mean (95% Confidence Interval) [Percentage Change]
    -2.08
    -4.04
    -6.59
    -6.34
    -1.74
    -3.74
    -2.39
    0.53
    -2.73
    -0.26
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 2.47
    Confidence Interval (2-Sided) 95%
    -0.93 to 5.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    29. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months
    Description Percentage change from baseline in biochemical marker of bone turnover (u-NTx) at 36 Months
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 15 13 16 13 11 10 18 14 17
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -17.43
    -55.12
    -11.90
    -57.17
    -12.15
    -49.10
    14.26
    -52.11
    27.55
    -50.51
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -78.06
    Confidence Interval (2-Sided) 95%
    -119.20 to -36.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    30. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months
    Description Percentage change from baseline in biochemical marker of bone turnover (s-CTx) at 36 Months
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 15 13 16 13 11 9 18 14 17
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -0.09
    -41.30
    -4.69
    -44.62
    18.24
    -26.26
    61.14
    -36.71
    10.32
    -23.93
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -34.25
    Confidence Interval (2-Sided) 95%
    -78.70 to 10.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    31. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months
    Description Percentage change from baseline in biochemical marker of bone turnover u-DPyr at 36 Months
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 15 13 14 13 11 10 18 14 17
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -18.69
    -14.95
    -7.82
    -26.27
    -4.69
    0.43
    -9.16
    -16.41
    22.41
    -16.84
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -39.25
    Confidence Interval (2-Sided) 95%
    -87.17 to 8.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    32. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 16 14 16 13 11 12 18 14 17
    Least Squares Mean (95% Confidence Interval) [Geometric Mean Percent Change]
    7.73
    10.86
    14.26
    9.13
    12.95
    8.49
    33.74
    11.12
    1.30
    17.90
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 16.59
    Confidence Interval (2-Sided) 95%
    -5.67 to 38.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    33. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 16 14 15 13 11 12 18 14 17
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    -20.79
    -18.79
    -13.11
    -21.08
    8.58
    12.44
    22.57
    -8.14
    -0.77
    -6.20
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value -5.43
    Confidence Interval (2-Sided) 95%
    -42.04 to 31.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    34. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 25 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 10 11 10 12 10 9 10 15 10 15
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    52.98
    52.37
    33.25
    59.37
    56.71
    82.94
    56.42
    77.90
    47.61
    96.70
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square Means
    Estimated Value 49.10
    Confidence Interval (2-Sided) 95%
    13.37 to 84.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    35. Secondary Outcome
    Title Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo / Placebo-Ext 2 Placebo / Odanacatib 50 Mg-Ext 2 Odanacatib 3 mg / Placebo-Ext 2 Odanacatib 3 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 10 mg / Placebo-Ext 2 Odanacatib 10 mg / Odanacatib 50 Mg-Ext 2 Odanacatib 25 mg / Placebo 50 Mg-Ext 2 Odanacatib 25 mg / 50 Mg-Ext 2 Odanacatib 50 mg / Placebo-Ext 2 Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Arm/Group Description During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. 12 Month Extension (Year 3) During this 12 month extension patients in this treatment group took one placebo tablet once a week. Patients in this treatment group took one 25 mg tablet of MK0822 once a week during 2 years and one placebo tablet once a week during the 3rd year. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years.
    Measure Participants 14 13 14 16 12 11 11 19 15 18
    Least Squares Mean (95% Confidence Interval) [Percentage change]
    7.40
    193.91
    1.67
    187.37
    58.76
    188.50
    77.94
    231.93
    27.20
    236.64
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Odanacatib 50 mg / Placebo-Ext 2, Odanacatib 50 mg / Odanacatib 50 Mg-Ext 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares Means
    Estimated Value 209.44
    Confidence Interval (2-Sided) 95%
    127.14 to 291.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    36. Primary Outcome
    Title Percentage Change From Baseline in Lumbar Spine BMD at 60 Months
    Description Percentage change from baseline in lumbar spine BMD at 60 months.
    Time Frame Baseline and Month 60

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Placebo Once Weekly Odanacatib 50 mg Once Weekly
    Arm/Group Description One placebo tablet once a week One odanacatib 50 mg tablet once a week
    Measure Participants 14 13
    Mean (95% Confidence Interval) [Percentage change]
    -0.41
    11.88
    37. Primary Outcome
    Title Percentage Change From Baseline in Lumbar Spine BMD at 120 Months
    Description Percentage change from baseline in lumbar spine BMD at 120 Months.
    Time Frame Baseline and Month 120

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Group A: Odanacatib 50 mg Once Weekly Group B: Odanacatib 50 mg Once Weekly Group C: Odanacatib 50 mg Once Weekly Group D: Odanacatib 50 mg Once Weekly
    Arm/Group Description Group A consists of a combination of participants who were treated with odanacatib 25 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 50 mg for 10 years. Group B consists of a combination participants who were treated with placebo for 2 years, then odanacatib 50 mg for 8 years; participants who were treated with odanacatib 3 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 10 mg for 2 years, then odanacatib 50 mg for 8 years. Group C consists of a combination of participants who were treated with placebo for 3 years, then odanacatib 50 mg for 7 years; and participants who were treated with odanacatib 3 mg for 2 years, then placebo for 1 year, then odanacatib 50 mg for 7 years. Group D consists of a combination of participants who were treated with odanacatib 10 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; participants who were treated with odanacatib 25 mg for 5 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; and participants who were treated with odanacatib 50 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years.
    Measure Participants 20 16 17 21
    Mean (95% Confidence Interval) [Percentage Change]
    16.92
    14.56
    17.18
    7.71
    38. Primary Outcome
    Title Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 administration of the trial drug during treatment years 6-10
    Arm/Group Title Group A: Odanacatib 50 mg Once Weekly Group B: Odanacatib 50 mg Once Weekly Group C: Odanacatib 50 mg Once Weekly Group D: Odanacatib 50 mg Once Weekly
    Arm/Group Description Group A consists of a combination of participants who were treated with odanacatib 25 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 50 mg for 10 years. Group B consists of a combination participants who were treated with placebo for 2 years, then odanacatib 50 mg for 8 years; participants who were treated with odanacatib 3 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 10 mg for 2 years, then odanacatib 50 mg for 8 years. Group C consists of a combination of participants who were treated with placebo for 3 years, then odanacatib 50 mg for 7 years; and participants who were treated with odanacatib 3 mg for 2 years, then placebo for 1 year, then odanacatib 50 mg for 7 years. Group D consists of a combination of participants who were treated with odanacatib 10 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; participants who were treated with odanacatib 25 mg for 5 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; and participants who were treated with odanacatib 50 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years.
    Measure Participants 28 34 23 32
    Number [Participants]
    27
    32.5%
    34
    41.5%
    23
    29.9%
    32
    40.5%
    39. Primary Outcome
    Title Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 administration of the trial drug during treatment years 6-10.
    Arm/Group Title Group A: Odanacatib 50 mg Once Weekly Group B: Odanacatib 50 mg Once Weekly Group C: Odanacatib 50 mg Once Weekly Group D: Odanacatib 50 mg Once Weekly
    Arm/Group Description Group A consists of a combination of participants who were treated with odanacatib 25 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 50 mg for 10 years. Group B consists of a combination participants who were treated with placebo for 2 years, then odanacatib 50 mg for 8 years; participants who were treated with odanacatib 3 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 10 mg for 2 years, then odanacatib 50 mg for 8 years Group C consists of a combination of participants who were treated with placebo for 3 years, then odanacatib 50 mg for 7 years; and participants who were treated with odanacatib 3 mg for 2 years, then placebo for 1 year, then odanacatib 50 mg for 7 years. Group D consists of a combination of participants who were treated with odanacatib 10 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; participants who were treated with odanacatib 25 mg for 5 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; and participants who were treated with odanacatib 50 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years.
    Measure Participants 28 34 23 32
    Number [Participants]
    1
    1.2%
    2
    2.4%
    0
    0%
    1
    1.3%

    Adverse Events

    Time Frame Adverse Events data were collected up to 120 months (from start of study medication, up to 14 days after the last dose).
    Adverse Event Reporting Description The Safety Analysis was based on the All Participants as Treated (APaT) population, which included all participants who took at least one dose of study medication.
    Arm/Group Title Years 1-2 Placebo/Placebo-Ext 1 Years 1-2 Odanacatib 3 mg/Odanacatib 3 Mg-Ext 1 Years 1-2 Odanacatib 10 mg/Odanacatib 10 Mg-Ext 1 Years 1-2 Odanacatib 25 mg/Odanacatib 25 Mg-Ext 1 Years 1-2 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 1 Year 3 Placebo/Placebo-Ext 2 Year 3 Placebo/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 3 mg/Placebo-Ext 2 Year 3 Odanacatib 3 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 10 mg/Placebo-Ext 2 Year 3 Odanacatib 10 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 25 mg/Placebo-Ext 2 Year 3 Odanacatib 25 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 50 mg/Placebo-Ext 2 Year 3 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 2 Years 4-5 Combined Group A.1: Odanacatib 50 mg Years 4-5 Combined Group A.2: Odanacatib 50 mg Years 4-5 Combined Group A.3: Placebo Years 6-10 Group A: Odanacatib 50 mg Once Weekly Years 6-10 Group B: Odanacatib 50 mg Once Weekly Years 6-10 Group C: Odanacatib 50 mg Once Weekly Years 6-10 Group D: Odanacatib 50 mg Once Weekly
    Arm/Group Description One placebo tablet once a week One odanacatib 3 mg tablet once a week One odanacatib 10 mg tablet once a week One odanacatib 25 mg tablet once a week One odanacatib 50 mg tablet once a week During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one placebo tablet once a week for 2 years. During this 12-month extension (Year 3), participants took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 3 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants took one placebo tablet once a week. Before entering this extension, participants had taken one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group took one 10 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 25 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants in this treatment group took one placebo tablet once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. During this 12-month extension (Year 3), participants took one 50 mg tablet of odanacatib once a week. Before entering this extension, participants in this treatment group had taken one 50 mg tablet of odanacatib once a week for 2 years. Combined Group A.1 consists of participants who received odanacatib 50 mg once a week during Year 3. During this 24-month extension (Years 4-5), these participants continued to receive odanacatib 50 mg once a week. Combined Group A.2 consists of participants who received placebo or odanacatib 3 mg in Years 1, 2 and 3. During this 24-month extension (Years 4-5), these participants received odanacatib 50 mg once a week. Combined Group A.3 consists of participants who, during this 24-month extension (Years 4-5), received placebo once a week. Group A consists of a combination of participants who were treated with odanacatib 25 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 50 mg for 10 years. Group B consists of a combination participants who were treated with placebo for 2 years, then odanacatib 50 mg for 8 years; participants who were treated with odanacatib 3 mg for 2 years, then odanacatib 50 mg for 8 years; and participants who were treated with odanacatib 10 mg for 2 years, then odanacatib 50 mg for 8 years. Group C consists of a combination of participants who were treated with placebo for 3 years, then odanacatib 50 mg for 7 years; and participants who were treated with odanacatib 3 mg for 2 years, then placebo for 1 year, then odanacatib 50 mg for 7 years Group D consists of a combination of participants who were treated with odanacatib 10 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; participants who were treated with odanacatib 25 mg for 5 years, then placebo for 3 years, then odanacatib 50 mg for 5 years; and participants who were treated with odanacatib 50 mg for 2 years, then placebo for 3 years, then odanacatib 50 mg for 5 years.
    All Cause Mortality
    Years 1-2 Placebo/Placebo-Ext 1 Years 1-2 Odanacatib 3 mg/Odanacatib 3 Mg-Ext 1 Years 1-2 Odanacatib 10 mg/Odanacatib 10 Mg-Ext 1 Years 1-2 Odanacatib 25 mg/Odanacatib 25 Mg-Ext 1 Years 1-2 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 1 Year 3 Placebo/Placebo-Ext 2 Year 3 Placebo/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 3 mg/Placebo-Ext 2 Year 3 Odanacatib 3 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 10 mg/Placebo-Ext 2 Year 3 Odanacatib 10 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 25 mg/Placebo-Ext 2 Year 3 Odanacatib 25 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 50 mg/Placebo-Ext 2 Year 3 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 2 Years 4-5 Combined Group A.1: Odanacatib 50 mg Years 4-5 Combined Group A.2: Odanacatib 50 mg Years 4-5 Combined Group A.3: Placebo Years 6-10 Group A: Odanacatib 50 mg Once Weekly Years 6-10 Group B: Odanacatib 50 mg Once Weekly Years 6-10 Group C: Odanacatib 50 mg Once Weekly Years 6-10 Group D: Odanacatib 50 mg Once Weekly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Years 1-2 Placebo/Placebo-Ext 1 Years 1-2 Odanacatib 3 mg/Odanacatib 3 Mg-Ext 1 Years 1-2 Odanacatib 10 mg/Odanacatib 10 Mg-Ext 1 Years 1-2 Odanacatib 25 mg/Odanacatib 25 Mg-Ext 1 Years 1-2 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 1 Year 3 Placebo/Placebo-Ext 2 Year 3 Placebo/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 3 mg/Placebo-Ext 2 Year 3 Odanacatib 3 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 10 mg/Placebo-Ext 2 Year 3 Odanacatib 10 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 25 mg/Placebo-Ext 2 Year 3 Odanacatib 25 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 50 mg/Placebo-Ext 2 Year 3 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 2 Years 4-5 Combined Group A.1: Odanacatib 50 mg Years 4-5 Combined Group A.2: Odanacatib 50 mg Years 4-5 Combined Group A.3: Placebo Years 6-10 Group A: Odanacatib 50 mg Once Weekly Years 6-10 Group B: Odanacatib 50 mg Once Weekly Years 6-10 Group C: Odanacatib 50 mg Once Weekly Years 6-10 Group D: Odanacatib 50 mg Once Weekly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/83 (9.6%) 12/82 (14.6%) 10/77 (13%) 9/79 (11.4%) 14/78 (17.9%) 2/19 (10.5%) 2/22 (9.1%) 3/18 (16.7%) 2/17 (11.8%) 1/18 (5.6%) 1/17 (5.9%) 2/19 (10.5%) 3/21 (14.3%) 2/18 (11.1%) 1/20 (5%) 16/73 (21.9%) 2/27 (7.4%) 8/41 (19.5%) 8/28 (28.6%) 14/34 (41.2%) 6/23 (26.1%) 12/32 (37.5%)
    Blood and lymphatic system disorders
    Immune thrombocytopenic purpura 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Cardiac disorders
    Arteriospasm Coronary 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Cardiac Failure Congestive 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 4 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Coronary Artery Occlusion 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Myocardial Infarction 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Atrial Fibrillation 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 2/34 (5.9%) 2 0/23 (0%) 0 0/32 (0%) 0
    Cardiac Failure 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Coronary Artery Disease 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Tachycardia 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Palpitations 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Vertigo positional 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Endocrine disorders
    Hypoparathyroidism secondary 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Eye disorders
    Macular Hole 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Retinal Detachment 1/83 (1.2%) 2 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Cataract 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 2 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Gastrointestinal disorders
    Anal Fistula 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Colitis 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Gastritis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Hiatus Hernia 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Oesophagitis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pancreatitis 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Peritonitis 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Stomatitis 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Abdominal Pain 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Abdominal Pain Lower 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Anal Sphincter Atony 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Flatulence 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Gastrooesophageal Reflux Disease 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Inguinal Hernia 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Gastric ulcer haemorrhage 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Nausea 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Vomiting 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    General disorders
    Chest Pain 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Non-cardiac chest pain 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Cholelithiasis 0/83 (0%) 0 0/82 (0%) 0 2/77 (2.6%) 2 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Infections and infestations
    Bronchitis 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Cellulitis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 3 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Diverticulitis 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Ear Infection 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pneumonia 1/83 (1.2%) 1 1/82 (1.2%) 1 1/77 (1.3%) 1 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pneumonia Streptococcal 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Viral Infection 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Respiratory Tract Infection 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Urinary Tract Infection 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Wound Infection 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Gastroenteritis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pyelonephritis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Sialoadenitis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Arthritis bacterial 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Bacterial sepsis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Diverticulitis intestinal haemorrhagic 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Infective exacerbation of chronic obstructive airways disease 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Injury, poisoning and procedural complications
    Hip Fracture 0/83 (0%) 0 1/82 (1.2%) 1 1/77 (1.3%) 1 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Joint Dislocation 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Lumbar Vertebral Fracture 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Post Procedural Bile Leak 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Head Injury 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Wrist Fracture 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Ankle Fracture 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Fall 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Rib Fracture 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Femur fracture 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 2 1/23 (4.3%) 1 0/32 (0%) 0
    Incarcerated incisional hernia 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Scar 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Urinary retention postoperative 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Investigations
    Electrocardiogram ST-T Change 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Weight Decreased 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Musculoskeletal and connective tissue disorders
    Foot Deformity 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Musculoskeletal Pain 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Osteoarthritis 1/83 (1.2%) 1 1/82 (1.2%) 1 1/77 (1.3%) 1 0/79 (0%) 0 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 4/73 (5.5%) 4 0/27 (0%) 0 1/41 (2.4%) 1 1/28 (3.6%) 1 1/34 (2.9%) 1 0/23 (0%) 0 1/32 (3.1%) 1
    Osteoporotic Fracture 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Intervertebral Disc Degeneration 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Musculoskeletal Chest Pain 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Trigger Finger 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Back Pain 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Lumbar Spinal Stenosis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Bursitis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Rotator cuff syndrome 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Spinal pain 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anal Cancer 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Basal Cell Carcinoma 1/83 (1.2%) 1 1/82 (1.2%) 2 1/77 (1.3%) 1 1/79 (1.3%) 2 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 2 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 3/41 (7.3%) 4 2/28 (7.1%) 5 1/34 (2.9%) 1 0/23 (0%) 0 1/32 (3.1%) 1
    Breast Cancer 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Breast Cancer In Situ 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Non-Hodgkin's Lymphoma 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Papillary Thyroid Cancer 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Sarcoma 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Squamous Cell Carcinoma 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Colon Cancer Metastatic 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Ovarian Neoplasm 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Colon Adenoma 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Neurilemmoma Benign 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Bowen's disease 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 1/32 (3.1%) 1
    Gastric cancer 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Invasive breast carcinoma 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Invasive ductal breast carcinoma 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Malignant melanoma 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 1/32 (3.1%) 1
    Malignant melanoma in situ 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Ovarian cancer 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Pancreatic carcinoma metastatic 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Squamous cell carcinoma of skin 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Nervous system disorders
    Reversible Ischaemic Neurological Deficit 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Syncope 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    VIIth Nerve Paralysis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Sciatica 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Cerebral infarction 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Cerebrovascular accident 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Dementia Alzheimer's type 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Headache 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Nerve root compression 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Paraesthesia 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Presyncope 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Renal and urinary disorders
    Nephrolithiasis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Chronic Kidney Disease 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Reproductive system and breast disorders
    Genital Prolapse 2/83 (2.4%) 2 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Ovarian cyst 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Ovarian cyst torsion 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Uterine prolapse 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Vaginal prolapse 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Chronic Obstructive Pulmonary Disease 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pneumothorax 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pulmonary embolism 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Skin and subcutaneous tissue disorders
    Erythema Nodosum 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Vascular disorders
    Hypertension 0/83 (0%) 0 0/82 (0%) 0 2/77 (2.6%) 2 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Orthostatic Hypotension 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Hypotension 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Other (Not Including Serious) Adverse Events
    Years 1-2 Placebo/Placebo-Ext 1 Years 1-2 Odanacatib 3 mg/Odanacatib 3 Mg-Ext 1 Years 1-2 Odanacatib 10 mg/Odanacatib 10 Mg-Ext 1 Years 1-2 Odanacatib 25 mg/Odanacatib 25 Mg-Ext 1 Years 1-2 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 1 Year 3 Placebo/Placebo-Ext 2 Year 3 Placebo/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 3 mg/Placebo-Ext 2 Year 3 Odanacatib 3 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 10 mg/Placebo-Ext 2 Year 3 Odanacatib 10 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 25 mg/Placebo-Ext 2 Year 3 Odanacatib 25 mg/Odanacatib 50 Mg-Ext 2 Year 3 Odanacatib 50 mg/Placebo-Ext 2 Year 3 Odanacatib 50 mg/Odanacatib 50 Mg-Ext 2 Years 4-5 Combined Group A.1: Odanacatib 50 mg Years 4-5 Combined Group A.2: Odanacatib 50 mg Years 4-5 Combined Group A.3: Placebo Years 6-10 Group A: Odanacatib 50 mg Once Weekly Years 6-10 Group B: Odanacatib 50 mg Once Weekly Years 6-10 Group C: Odanacatib 50 mg Once Weekly Years 6-10 Group D: Odanacatib 50 mg Once Weekly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 68/83 (81.9%) 66/82 (80.5%) 67/77 (87%) 67/79 (84.8%) 66/78 (84.6%) 17/19 (89.5%) 13/22 (59.1%) 16/18 (88.9%) 14/17 (82.4%) 13/18 (72.2%) 15/17 (88.2%) 15/19 (78.9%) 17/21 (81%) 14/18 (77.8%) 15/20 (75%) 64/73 (87.7%) 24/27 (88.9%) 33/41 (80.5%) 25/28 (89.3%) 31/34 (91.2%) 23/23 (100%) 30/32 (93.8%)
    Cardiac disorders
    Palpitations 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 2 5/78 (6.4%) 5 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 1/18 (5.6%) 1 0/20 (0%) 0 1/73 (1.4%) 1 1/27 (3.7%) 1 1/41 (2.4%) 1 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Arrhythmia 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Atrial Flutter 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Mitral Valve Prolapse 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Tachycardia 1/83 (1.2%) 1 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Ear and labyrinth disorders
    Deafness 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Tinnitus 2/83 (2.4%) 2 1/82 (1.2%) 1 2/77 (2.6%) 2 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 0/28 (0%) 0 2/34 (5.9%) 3 2/23 (8.7%) 2 0/32 (0%) 0
    Tympanosclerosis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Vertigo 4/83 (4.8%) 5 0/82 (0%) 0 3/77 (3.9%) 3 1/79 (1.3%) 1 3/78 (3.8%) 3 1/19 (5.3%) 1 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 2/18 (11.1%) 2 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 5/34 (14.7%) 7 1/23 (4.3%) 1 1/32 (3.1%) 1
    Vertigo Positional 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Endocrine disorders
    Hypothyroidism 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Thyroiditis Chronic 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Eye disorders
    Cataract 2/83 (2.4%) 2 2/82 (2.4%) 2 4/77 (5.2%) 4 0/79 (0%) 0 2/78 (2.6%) 3 0/19 (0%) 0 1/22 (4.5%) 1 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 2/19 (10.5%) 3 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 2/73 (2.7%) 2 2/27 (7.4%) 4 3/41 (7.3%) 3 0/28 (0%) 0 6/34 (17.6%) 9 6/23 (26.1%) 10 1/32 (3.1%) 1
    Conjunctivitis Allergic 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Eye Pruritus 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Macular Degeneration 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Eyelid Ptosis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Gastrointestinal disorders
    Abdominal Pain Upper 2/83 (2.4%) 2 5/82 (6.1%) 5 5/77 (6.5%) 5 0/79 (0%) 0 5/78 (6.4%) 7 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 2/27 (7.4%) 2 0/41 (0%) 0 1/28 (3.6%) 1 1/34 (2.9%) 1 1/23 (4.3%) 1 3/32 (9.4%) 4
    Constipation 3/83 (3.6%) 3 8/82 (9.8%) 8 6/77 (7.8%) 7 3/79 (3.8%) 3 1/78 (1.3%) 1 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 3/73 (4.1%) 4 1/27 (3.7%) 1 0/41 (0%) 0 2/28 (7.1%) 3 2/34 (5.9%) 2 1/23 (4.3%) 2 1/32 (3.1%) 1
    Diarrhoea 7/83 (8.4%) 7 4/82 (4.9%) 5 8/77 (10.4%) 8 3/79 (3.8%) 3 7/78 (9%) 10 1/19 (5.3%) 1 2/22 (9.1%) 2 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 3/20 (15%) 3 2/73 (2.7%) 3 3/27 (11.1%) 3 0/41 (0%) 0 2/28 (7.1%) 2 2/34 (5.9%) 3 4/23 (17.4%) 5 2/32 (6.3%) 2
    Dyspepsia 4/83 (4.8%) 6 2/82 (2.4%) 3 3/77 (3.9%) 4 3/79 (3.8%) 3 5/78 (6.4%) 5 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 3/73 (4.1%) 4 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 4/23 (17.4%) 4 3/32 (9.4%) 3
    Gastrooesophageal Reflux Disease 1/83 (1.2%) 1 3/82 (3.7%) 3 4/77 (5.2%) 4 5/79 (6.3%) 7 3/78 (3.8%) 3 2/19 (10.5%) 2 2/22 (9.1%) 2 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 2/21 (9.5%) 2 0/18 (0%) 0 1/20 (5%) 1 3/73 (4.1%) 3 2/27 (7.4%) 2 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 2/23 (8.7%) 2 2/32 (6.3%) 2
    Nausea 8/83 (9.6%) 8 4/82 (4.9%) 6 6/77 (7.8%) 7 6/79 (7.6%) 7 5/78 (6.4%) 7 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 2/27 (7.4%) 2 1/41 (2.4%) 1 1/28 (3.6%) 1 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Toothache 4/83 (4.8%) 7 3/82 (3.7%) 4 4/77 (5.2%) 6 2/79 (2.5%) 2 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 4/73 (5.5%) 4 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Abdominal Pain 1/83 (1.2%) 1 0/82 (0%) 0 2/77 (2.6%) 2 2/79 (2.5%) 4 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 2/17 (11.8%) 2 0/19 (0%) 0 2/21 (9.5%) 2 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 2/41 (4.9%) 3 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 2/32 (6.3%) 3
    Anal Fissure 1/83 (1.2%) 1 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Aphthous Ulcer 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 4 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Dry Mouth 0/83 (0%) 0 2/82 (2.4%) 2 2/77 (2.6%) 2 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 1/41 (2.4%) 1 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Duodenal Ulcer 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Faecal Incontinence 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Flatulence 1/83 (1.2%) 1 0/82 (0%) 0 1/77 (1.3%) 1 2/79 (2.5%) 2 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Gastric Disorder 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Gastric Polyps 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Gastric Ulcer 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Gastritis 0/83 (0%) 0 3/82 (3.7%) 3 0/77 (0%) 0 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 2/20 (10%) 2 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 1/28 (3.6%) 1 2/34 (5.9%) 2 1/23 (4.3%) 1 0/32 (0%) 0
    Gingival Swelling 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Inguinal Hernia 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 2 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Irritable Bowel Syndrome 1/83 (1.2%) 1 0/82 (0%) 0 3/77 (3.9%) 3 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 1/18 (5.6%) 1 1/17 (5.9%) 3 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Mouth Ulceration 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Oesophagitis 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 2 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 2 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 3/34 (8.8%) 3 0/23 (0%) 0 0/32 (0%) 0
    Rectal Haemorrhage 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 2/79 (2.5%) 4 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 1/73 (1.4%) 2 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Upper Gastrointestinal Haemorrhage 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Vomiting 1/83 (1.2%) 1 1/82 (1.2%) 1 3/77 (3.9%) 3 4/79 (5.1%) 4 1/78 (1.3%) 1 1/19 (5.3%) 1 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 2/73 (2.7%) 2 1/27 (3.7%) 1 1/41 (2.4%) 1 0/28 (0%) 0 1/34 (2.9%) 1 1/23 (4.3%) 1 0/32 (0%) 0
    General disorders
    Fatigue 6/83 (7.2%) 6 2/82 (2.4%) 2 2/77 (2.6%) 2 1/79 (1.3%) 1 3/78 (3.8%) 3 1/19 (5.3%) 1 1/22 (4.5%) 2 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 2/73 (2.7%) 3 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Influenza Like Illness 3/83 (3.6%) 3 1/82 (1.2%) 1 3/77 (3.9%) 5 2/79 (2.5%) 2 6/78 (7.7%) 7 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 1/73 (1.4%) 2 1/27 (3.7%) 1 0/41 (0%) 0 1/28 (3.6%) 1 1/34 (2.9%) 1 1/23 (4.3%) 1 0/32 (0%) 0
    Calcinosis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Chest Discomfort 1/83 (1.2%) 1 2/82 (2.4%) 3 0/77 (0%) 0 2/79 (2.5%) 2 2/78 (2.6%) 2 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Chest Pain 4/83 (4.8%) 8 1/82 (1.2%) 1 1/77 (1.3%) 1 2/79 (2.5%) 2 3/78 (3.8%) 3 2/19 (10.5%) 2 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 0/18 (0%) 0 1/20 (5%) 1 1/73 (1.4%) 1 1/27 (3.7%) 1 1/41 (2.4%) 1 2/28 (7.1%) 3 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Oedema Peripheral 3/83 (3.6%) 3 1/82 (1.2%) 1 1/77 (1.3%) 1 2/79 (2.5%) 2 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 1/17 (5.9%) 1 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 3/20 (15%) 3 2/73 (2.7%) 2 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 2 2/34 (5.9%) 2 2/23 (8.7%) 3 0/32 (0%) 0
    Immune system disorders
    Allergy To Arthropod Sting 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Infections and infestations
    Bronchitis 2/83 (2.4%) 5 4/82 (4.9%) 6 4/77 (5.2%) 5 2/79 (2.5%) 2 1/78 (1.3%) 2 1/19 (5.3%) 1 2/22 (9.1%) 3 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 3 1/19 (5.3%) 1 1/21 (4.8%) 1 1/18 (5.6%) 1 0/20 (0%) 0 4/73 (5.5%) 7 4/27 (14.8%) 4 4/41 (9.8%) 4 3/28 (10.7%) 4 5/34 (14.7%) 6 5/23 (21.7%) 9 5/32 (15.6%) 5
    Cystitis 1/83 (1.2%) 3 6/82 (7.3%) 6 3/77 (3.9%) 3 1/79 (1.3%) 2 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 1/21 (4.8%) 1 0/18 (0%) 0 2/20 (10%) 2 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 1/28 (3.6%) 1 0/34 (0%) 0 2/23 (8.7%) 2 0/32 (0%) 0
    Gastroenteritis 3/83 (3.6%) 4 2/82 (2.4%) 3 1/77 (1.3%) 1 4/79 (5.1%) 4 1/78 (1.3%) 1 1/19 (5.3%) 1 1/22 (4.5%) 1 2/18 (11.1%) 2 0/17 (0%) 0 1/18 (5.6%) 1 1/17 (5.9%) 1 0/19 (0%) 0 1/21 (4.8%) 1 1/18 (5.6%) 1 0/20 (0%) 0 2/73 (2.7%) 2 2/27 (7.4%) 2 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 1/23 (4.3%) 1 1/32 (3.1%) 1
    Pharyngitis 4/83 (4.8%) 4 2/82 (2.4%) 2 4/77 (5.2%) 4 2/79 (2.5%) 2 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 2/19 (10.5%) 2 1/21 (4.8%) 1 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 2 1/32 (3.1%) 1
    Sinusitis 4/83 (4.8%) 4 4/82 (4.9%) 4 5/77 (6.5%) 6 4/79 (5.1%) 5 5/78 (6.4%) 6 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 2 1/17 (5.9%) 1 2/18 (11.1%) 2 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 3/73 (4.1%) 3 3/27 (11.1%) 5 2/41 (4.9%) 2 1/28 (3.6%) 1 1/34 (2.9%) 2 4/23 (17.4%) 4 0/32 (0%) 0
    Upper Respiratory Tract Infection 9/83 (10.8%) 11 10/82 (12.2%) 12 7/77 (9.1%) 9 7/79 (8.9%) 11 10/78 (12.8%) 14 1/19 (5.3%) 1 0/22 (0%) 0 3/18 (16.7%) 4 2/17 (11.8%) 2 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 2/21 (9.5%) 3 0/18 (0%) 0 0/20 (0%) 0 3/73 (4.1%) 4 0/27 (0%) 0 1/41 (2.4%) 1 2/28 (7.1%) 7 3/34 (8.8%) 5 2/23 (8.7%) 2 2/32 (6.3%) 2
    Urinary Tract Infection 11/83 (13.3%) 17 6/82 (7.3%) 7 7/77 (9.1%) 7 8/79 (10.1%) 10 12/78 (15.4%) 15 1/19 (5.3%) 1 2/22 (9.1%) 3 1/18 (5.6%) 1 2/17 (11.8%) 2 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 3/21 (14.3%) 3 0/18 (0%) 0 2/20 (10%) 3 10/73 (13.7%) 12 4/27 (14.8%) 4 2/41 (4.9%) 3 9/28 (32.1%) 15 9/34 (26.5%) 19 6/23 (26.1%) 20 7/32 (21.9%) 15
    Bacterial Infection 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Cellulitis 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Chronic Sinusitis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Ear Infection 0/83 (0%) 0 2/82 (2.4%) 4 1/77 (1.3%) 1 1/79 (1.3%) 1 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 1/21 (4.8%) 1 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 1/41 (2.4%) 1 1/28 (3.6%) 1 2/34 (5.9%) 2 0/23 (0%) 0 1/32 (3.1%) 1
    Eye Infection 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 2/79 (2.5%) 2 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 2/32 (6.3%) 2
    Fungal Infection 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Furuncle 1/83 (1.2%) 1 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Herpes Zoster 1/83 (1.2%) 1 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 2/34 (5.9%) 2 1/23 (4.3%) 1 0/32 (0%) 0
    Influenza 1/83 (1.2%) 1 3/82 (3.7%) 3 1/77 (1.3%) 1 2/79 (2.5%) 2 3/78 (3.8%) 3 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 2/21 (9.5%) 2 0/18 (0%) 0 0/20 (0%) 0 4/73 (5.5%) 4 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 4/34 (11.8%) 4 0/23 (0%) 0 5/32 (15.6%) 7
    Nasal Abscess 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 2 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Nasopharyngitis 14/83 (16.9%) 20 9/82 (11%) 13 16/77 (20.8%) 20 8/79 (10.1%) 10 14/78 (17.9%) 23 1/19 (5.3%) 1 4/22 (18.2%) 5 2/18 (11.1%) 3 2/17 (11.8%) 2 3/18 (16.7%) 3 0/17 (0%) 0 2/19 (10.5%) 2 3/21 (14.3%) 3 1/18 (5.6%) 1 1/20 (5%) 2 13/73 (17.8%) 16 6/27 (22.2%) 13 10/41 (24.4%) 13 7/28 (25%) 9 8/34 (23.5%) 15 5/23 (21.7%) 9 9/32 (28.1%) 20
    Onychomycosis 0/83 (0%) 0 1/82 (1.2%) 1 1/77 (1.3%) 1 0/79 (0%) 0 1/78 (1.3%) 1 1/19 (5.3%) 2 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 2/73 (2.7%) 2 1/27 (3.7%) 1 0/41 (0%) 0 0/28 (0%) 0 2/34 (5.9%) 3 3/23 (13%) 4 1/32 (3.1%) 2
    Oral Candidiasis 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 1/79 (1.3%) 2 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 1/32 (3.1%) 1
    Oral Herpes 1/83 (1.2%) 1 2/82 (2.4%) 2 0/77 (0%) 0 2/79 (2.5%) 2 2/78 (2.6%) 5 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 1/20 (5%) 1 2/73 (2.7%) 2 0/27 (0%) 0 0/41 (0%) 0 2/28 (7.1%) 2 1/34 (2.9%) 1 0/23 (0%) 0 1/32 (3.1%) 2
    Otitis Media Acute 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Pharyngitis Streptococcal 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pneumonia 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 1/27 (3.7%) 1 2/41 (4.9%) 3 0/28 (0%) 0 1/34 (2.9%) 3 1/23 (4.3%) 1 3/32 (9.4%) 4
    Pyoderma 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Respiratory Tract Infection 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 2 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 1/23 (4.3%) 2 0/32 (0%) 0
    Respiratory Tract Infection Viral 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 0/79 (0%) 0 1/78 (1.3%) 1 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Rhinitis 1/83 (1.2%) 1 3/82 (3.7%) 3 1/77 (1.3%) 1 1/79 (1.3%) 1 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 2/28 (7.1%) 2 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Tooth Abscess 1/83 (1.2%) 1 0/82 (0%) 0 2/77 (2.6%) 2 2/79 (2.5%) 2 3/78 (3.8%) 3 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Tooth Infection 0/83 (0%) 0 0/82 (0%) 0 2/77 (2.6%) 2 3/79 (3.8%) 3 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Viral Infection 1/83 (1.2%) 2 0/82 (0%) 0 0/77 (0%) 0 4/79 (5.1%) 4 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 2/73 (2.7%) 2 1/27 (3.7%) 1 0/41 (0%) 0 1/28 (3.6%) 1 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Viral Upper Respiratory Tract Infection 1/83 (1.2%) 2 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 5/83 (6%) 5 2/82 (2.4%) 4 5/77 (6.5%) 8 2/79 (2.5%) 3 3/78 (3.8%) 3 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 2 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 4/73 (5.5%) 6 0/27 (0%) 0 2/41 (4.9%) 2 3/28 (10.7%) 3 0/34 (0%) 0 1/23 (4.3%) 2 3/32 (9.4%) 7
    Arthropod Bite 0/83 (0%) 0 3/82 (3.7%) 3 2/77 (2.6%) 2 1/79 (1.3%) 2 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 2 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Arthropod Sting 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 1/41 (2.4%) 2 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Epicondylitis 1/83 (1.2%) 1 2/82 (2.4%) 2 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 2/28 (7.1%) 2 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Fall 2/83 (2.4%) 3 2/82 (2.4%) 2 1/77 (1.3%) 1 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 2/18 (11.1%) 2 0/20 (0%) 0 3/73 (4.1%) 4 0/27 (0%) 0 2/41 (4.9%) 2 3/28 (10.7%) 13 4/34 (11.8%) 8 5/23 (21.7%) 6 4/32 (12.5%) 9
    Humerus Fracture 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 2 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Ligament Sprain 4/83 (4.8%) 4 1/82 (1.2%) 1 2/77 (2.6%) 2 3/79 (3.8%) 3 3/78 (3.8%) 5 0/19 (0%) 0 2/22 (9.1%) 2 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Limb Injury 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 1/18 (5.6%) 2 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 1/23 (4.3%) 1 0/32 (0%) 0
    Muscle Strain 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 4/79 (5.1%) 5 1/78 (1.3%) 2 1/19 (5.3%) 1 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 2/41 (4.9%) 2 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Wound 0/83 (0%) 0 2/82 (2.4%) 2 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Procedural Pain 1/83 (1.2%) 1 2/82 (2.4%) 2 2/77 (2.6%) 3 0/79 (0%) 0 2/78 (2.6%) 3 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 2 0/19 (0%) 0 1/21 (4.8%) 2 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Radius Fracture 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 2/27 (7.4%) 2 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Laceration 0/83 (0%) 0 0/82 (0%) 0 2/77 (2.6%) 2 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 2/22 (9.1%) 2 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Skull Fractured Base 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Spinal Compression Fracture 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Spinal Fracture 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Subdural Haematoma 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Thoracic Vertebral Fracture 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Tooth Fracture 1/83 (1.2%) 1 1/82 (1.2%) 1 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 2 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Wrist Fracture 2/83 (2.4%) 2 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 1/21 (4.8%) 1 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Investigations
    Alanine Aminotransferase Increased 1/83 (1.2%) 1 3/82 (3.7%) 4 0/77 (0%) 0 5/79 (6.3%) 7 2/78 (2.6%) 3 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 4/23 (17.4%) 4 3/32 (9.4%) 3
    Aspartate Aminotransferase Increased 1/83 (1.2%) 1 3/82 (3.7%) 5 2/77 (2.6%) 2 4/79 (5.1%) 6 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 1/27 (3.7%) 1 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 4/23 (17.4%) 4 2/32 (6.3%) 2
    Weight Decreased 2/83 (2.4%) 2 1/82 (1.2%) 1 2/77 (2.6%) 2 1/79 (1.3%) 1 4/78 (5.1%) 4 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 1/73 (1.4%) 1 1/27 (3.7%) 1 1/41 (2.4%) 1 0/28 (0%) 0 2/34 (5.9%) 3 2/23 (8.7%) 2 2/32 (6.3%) 2
    Weight Increased 4/83 (4.8%) 4 2/82 (2.4%) 2 3/77 (3.9%) 3 5/79 (6.3%) 6 3/78 (3.8%) 3 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Blood 1,25-Dihydroxycholecalciferol Increased 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 1/19 (5.3%) 2 0/22 (0%) 0 1/18 (5.6%) 1 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Blood Cholesterol Increased 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 2/17 (11.8%) 2 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 2/73 (2.7%) 2 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Blood Glucose Increased 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 2/79 (2.5%) 3 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 0
    Blood Parathyroid Hormone Increased 0/83 (0%) 0 1/82 (1.2%) 1 1/77 (1.3%) 1 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 2 1/22 (4.5%) 1 1/18 (5.6%) 1 1/17 (5.9%) 1 0/18 (0%) 0 1/17 (5.9%) 5 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 5/73 (6.8%) 13 3/27 (11.1%) 5 2/41 (4.9%) 3 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Blood Pressure Increased 0/83 (0%) 0 2/82 (2.4%) 2 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 2/21 (9.5%) 2 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Blood Triglycerides Increased 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 2/41 (4.9%) 2 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Carotid Bruit 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Glucose Urine Present 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    High Density Lipoprotein Decreased 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Lymphocyte Count Decreased 1/83 (1.2%) 1 0/82 (0%) 0 2/77 (2.6%) 2 1/79 (1.3%) 1 2/78 (2.6%) 3 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 3/18 (16.7%) 3 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    White Blood Cells Urine Positive 0/83 (0%) 0 2/82 (2.4%) 3 2/77 (2.6%) 2 0/79 (0%) 0 2/78 (2.6%) 2 1/19 (5.3%) 1 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Metabolism and nutrition disorders
    Dyslipidaemia 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 1/28 (3.6%) 1 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Hypercholesterolaemia 1/83 (1.2%) 1 3/82 (3.7%) 3 1/77 (1.3%) 1 3/79 (3.8%) 3 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 2/18 (11.1%) 2 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 0/18 (0%) 0 0/20 (0%) 0 2/73 (2.7%) 2 2/27 (7.4%) 2 0/41 (0%) 0 3/28 (10.7%) 3 1/34 (2.9%) 1 1/23 (4.3%) 1 4/32 (12.5%) 4
    Hyperlipidaemia 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 13/83 (15.7%) 24 12/82 (14.6%) 16 12/77 (15.6%) 13 14/79 (17.7%) 17 12/78 (15.4%) 14 3/19 (15.8%) 4 1/22 (4.5%) 1 1/18 (5.6%) 1 1/17 (5.9%) 1 1/18 (5.6%) 1 1/17 (5.9%) 2 2/19 (10.5%) 2 3/21 (14.3%) 4 0/18 (0%) 0 3/20 (15%) 4 9/73 (12.3%) 13 4/27 (14.8%) 4 6/41 (14.6%) 8 5/28 (17.9%) 10 4/34 (11.8%) 4 8/23 (34.8%) 8 3/32 (9.4%) 3
    Muscle Spasms 4/83 (4.8%) 4 7/82 (8.5%) 7 7/77 (9.1%) 7 3/79 (3.8%) 3 13/78 (16.7%) 16 1/19 (5.3%) 1 2/22 (9.1%) 3 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 1/18 (5.6%) 1 2/20 (10%) 2 3/73 (4.1%) 3 1/27 (3.7%) 1 1/41 (2.4%) 1 1/28 (3.6%) 1 1/34 (2.9%) 1 2/23 (8.7%) 2 1/32 (3.1%) 1
    Musculoskeletal Pain 5/83 (6%) 5 3/82 (3.7%) 3 5/77 (6.5%) 5 10/79 (12.7%) 11 4/78 (5.1%) 4 2/19 (10.5%) 2 1/22 (4.5%) 1 1/18 (5.6%) 1 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 3/21 (14.3%) 3 2/18 (11.1%) 2 0/20 (0%) 0 4/73 (5.5%) 5 1/27 (3.7%) 1 6/41 (14.6%) 6 3/28 (10.7%) 6 4/34 (11.8%) 4 5/23 (21.7%) 6 4/32 (12.5%) 4
    Myalgia 3/83 (3.6%) 3 2/82 (2.4%) 2 4/77 (5.2%) 4 3/79 (3.8%) 4 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 2/73 (2.7%) 2 1/27 (3.7%) 1 0/41 (0%) 0 1/28 (3.6%) 1 2/34 (5.9%) 2 2/23 (8.7%) 2 0/32 (0%) 0
    Neck Pain 3/83 (3.6%) 3 0/82 (0%) 0 2/77 (2.6%) 2 5/79 (6.3%) 5 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 2/21 (9.5%) 2 0/18 (0%) 0 4/20 (20%) 4 3/73 (4.1%) 3 2/27 (7.4%) 2 1/41 (2.4%) 1 0/28 (0%) 0 3/34 (8.8%) 4 3/23 (13%) 4 1/32 (3.1%) 1
    Osteoarthritis 2/83 (2.4%) 2 5/82 (6.1%) 5 4/77 (5.2%) 5 4/79 (5.1%) 4 5/78 (6.4%) 5 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 2/18 (11.1%) 2 1/17 (5.9%) 1 0/19 (0%) 0 3/21 (14.3%) 3 1/18 (5.6%) 2 1/20 (5%) 1 6/73 (8.2%) 7 2/27 (7.4%) 3 1/41 (2.4%) 2 3/28 (10.7%) 3 5/34 (14.7%) 6 2/23 (8.7%) 2 2/32 (6.3%) 2
    Tendonitis 1/83 (1.2%) 1 6/82 (7.3%) 6 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 1/73 (1.4%) 1 0/27 (0%) 0 1/41 (2.4%) 1 2/28 (7.1%) 2 3/34 (8.8%) 3 2/23 (8.7%) 2 2/32 (6.3%) 2
    Back Pain 10/83 (12%) 12 17/82 (20.7%) 19 9/77 (11.7%) 11 14/79 (17.7%) 19 11/78 (14.1%) 13 2/19 (10.5%) 2 5/22 (22.7%) 5 1/18 (5.6%) 1 2/17 (11.8%) 2 1/18 (5.6%) 1 1/17 (5.9%) 1 4/19 (21.1%) 5 2/21 (9.5%) 2 0/18 (0%) 0 0/20 (0%) 0 8/73 (11%) 11 5/27 (18.5%) 7 1/41 (2.4%) 1 6/28 (21.4%) 6 7/34 (20.6%) 9 5/23 (21.7%) 7 2/32 (6.3%) 2
    Bone Pain 1/83 (1.2%) 1 1/82 (1.2%) 1 2/77 (2.6%) 2 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 1/27 (3.7%) 1 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Bursitis 2/83 (2.4%) 2 2/82 (2.4%) 2 3/77 (3.9%) 3 3/79 (3.8%) 3 2/78 (2.6%) 2 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 2/17 (11.8%) 3 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 0/18 (0%) 0 1/20 (5%) 1 2/73 (2.7%) 2 2/27 (7.4%) 2 1/41 (2.4%) 1 1/28 (3.6%) 1 1/34 (2.9%) 1 1/23 (4.3%) 1 2/32 (6.3%) 2
    Costochondritis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Dupuytren's Contracture 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Foot Deformity 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 2/18 (11.1%) 2 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Joint Stiffness 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Monarthritis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Muscle Contracture 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Muscular Weakness 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 1/22 (4.5%) 2 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 2/34 (5.9%) 2 1/23 (4.3%) 1 0/32 (0%) 0
    Musculoskeletal Chest Pain 0/83 (0%) 0 0/82 (0%) 0 2/77 (2.6%) 2 3/79 (3.8%) 3 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 1/20 (5%) 1 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 3/32 (9.4%) 3
    Musculoskeletal Discomfort 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Musculoskeletal Stiffness 0/83 (0%) 0 0/82 (0%) 0 1/77 (1.3%) 1 1/79 (1.3%) 1 1/78 (1.3%) 1 1/19 (5.3%) 1 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 2 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Osteochondritis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Osteosclerosis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 2 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pain In Extremity 10/83 (12%) 13 8/82 (9.8%) 10 8/77 (10.4%) 8 11/79 (13.9%) 11 3/78 (3.8%) 5 1/19 (5.3%) 1 3/22 (13.6%) 4 1/18 (5.6%) 1 2/17 (11.8%) 2 3/18 (16.7%) 3 1/17 (5.9%) 1 3/19 (15.8%) 4 2/21 (9.5%) 2 1/18 (5.6%) 1 0/20 (0%) 0 12/73 (16.4%) 15 4/27 (14.8%) 5 2/41 (4.9%) 2 6/28 (21.4%) 6 1/34 (2.9%) 1 2/23 (8.7%) 3 7/32 (21.9%) 9
    Polyarthritis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Rotator Cuff Syndrome 1/83 (1.2%) 1 0/82 (0%) 0 3/77 (3.9%) 5 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 2/73 (2.7%) 2 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Sacroiliitis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Synovial Cyst 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 1/32 (3.1%) 1
    Torticollis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lipoma 0/83 (0%) 0 1/82 (1.2%) 1 1/77 (1.3%) 1 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Ovarian Neoplasm 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Nervous system disorders
    Dizziness 4/83 (4.8%) 5 7/82 (8.5%) 9 8/77 (10.4%) 10 3/79 (3.8%) 3 4/78 (5.1%) 4 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 1/17 (5.9%) 1 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 2/18 (11.1%) 3 1/20 (5%) 1 2/73 (2.7%) 3 0/27 (0%) 0 0/41 (0%) 0 2/28 (7.1%) 2 3/34 (8.8%) 3 2/23 (8.7%) 2 2/32 (6.3%) 2
    Headache 11/83 (13.3%) 13 9/82 (11%) 9 10/77 (13%) 10 9/79 (11.4%) 10 9/78 (11.5%) 12 0/19 (0%) 0 2/22 (9.1%) 2 1/18 (5.6%) 1 3/17 (17.6%) 3 1/18 (5.6%) 1 1/17 (5.9%) 1 1/19 (5.3%) 1 1/21 (4.8%) 1 1/18 (5.6%) 1 1/20 (5%) 1 2/73 (2.7%) 2 2/27 (7.4%) 2 1/41 (2.4%) 2 1/28 (3.6%) 1 2/34 (5.9%) 3 3/23 (13%) 4 3/32 (9.4%) 4
    Memory Impairment 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Migraine 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 2/73 (2.7%) 2 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 1/32 (3.1%) 1
    Paraesthesia 2/83 (2.4%) 2 0/82 (0%) 0 2/77 (2.6%) 2 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 1/21 (4.8%) 1 0/18 (0%) 0 1/20 (5%) 1 3/73 (4.1%) 3 1/27 (3.7%) 1 2/41 (4.9%) 3 1/28 (3.6%) 1 2/34 (5.9%) 2 1/23 (4.3%) 1 0/32 (0%) 0
    Sciatica 2/83 (2.4%) 2 2/82 (2.4%) 4 0/77 (0%) 0 1/79 (1.3%) 1 1/78 (1.3%) 1 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 1/17 (5.9%) 2 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 2/73 (2.7%) 3 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 1/32 (3.1%) 1
    Somnolence 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Tension Headache 0/83 (0%) 0 1/82 (1.2%) 1 1/77 (1.3%) 1 1/79 (1.3%) 1 0/78 (0%) 0 1/19 (5.3%) 1 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Tremor 1/83 (1.2%) 1 0/82 (0%) 0 1/77 (1.3%) 2 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 2/17 (11.8%) 2 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Trigeminal Neuralgia 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Psychiatric disorders
    Depression 5/83 (6%) 5 4/82 (4.9%) 4 5/77 (6.5%) 5 3/79 (3.8%) 3 3/78 (3.8%) 3 0/19 (0%) 0 2/22 (9.1%) 2 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 3/27 (11.1%) 3 1/41 (2.4%) 1 3/28 (10.7%) 3 4/34 (11.8%) 5 2/23 (8.7%) 4 2/32 (6.3%) 2
    Insomnia 7/83 (8.4%) 7 3/82 (3.7%) 4 4/77 (5.2%) 4 3/79 (3.8%) 3 6/78 (7.7%) 6 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 2/73 (2.7%) 2 0/27 (0%) 0 2/41 (4.9%) 2 2/28 (7.1%) 2 1/34 (2.9%) 1 1/23 (4.3%) 1 1/32 (3.1%) 1
    Alcoholism 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Anxiety 0/83 (0%) 0 0/82 (0%) 0 3/77 (3.9%) 3 1/79 (1.3%) 1 0/78 (0%) 0 2/19 (10.5%) 2 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 1/34 (2.9%) 1 1/23 (4.3%) 1 1/32 (3.1%) 1
    Dysthymic Disorder 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Stress 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 1/23 (4.3%) 1 0/32 (0%) 0
    Reproductive system and breast disorders
    Breast Mass 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Fibrocystic Breast Disease 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pelvic Pain 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Vulvovaginal Discomfort 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal Pain 2/83 (2.4%) 2 3/82 (3.7%) 3 3/77 (3.9%) 3 5/79 (6.3%) 5 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 3/73 (4.1%) 4 1/27 (3.7%) 1 2/41 (4.9%) 2 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 1/32 (3.1%) 2
    Asthma 0/83 (0%) 0 0/82 (0%) 0 2/77 (2.6%) 2 2/79 (2.5%) 2 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 3
    Cough 2/83 (2.4%) 4 2/82 (2.4%) 2 2/77 (2.6%) 5 3/79 (3.8%) 4 3/78 (3.8%) 3 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 2/17 (11.8%) 2 0/19 (0%) 0 1/21 (4.8%) 1 1/18 (5.6%) 1 1/20 (5%) 1 4/73 (5.5%) 4 0/27 (0%) 0 3/41 (7.3%) 3 0/28 (0%) 0 2/34 (5.9%) 2 0/23 (0%) 0 1/32 (3.1%) 1
    Dyspnoea 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 0/28 (0%) 0 3/34 (8.8%) 3 1/23 (4.3%) 1 0/32 (0%) 0
    Dyspnoea Exertional 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 1/41 (2.4%) 1 1/28 (3.6%) 1 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Emphysema 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 1/78 (1.3%) 1 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Haemoptysis 1/83 (1.2%) 2 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash 7/83 (8.4%) 10 4/82 (4.9%) 4 5/77 (6.5%) 6 2/79 (2.5%) 2 3/78 (3.8%) 3 2/19 (10.5%) 2 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 2/18 (11.1%) 2 1/20 (5%) 3 1/73 (1.4%) 2 1/27 (3.7%) 1 1/41 (2.4%) 1 0/28 (0%) 0 2/34 (5.9%) 2 2/23 (8.7%) 2 0/32 (0%) 0
    Actinic Keratosis 0/83 (0%) 0 1/82 (1.2%) 1 2/77 (2.6%) 2 2/79 (2.5%) 2 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 1 1/28 (3.6%) 1 2/34 (5.9%) 2 0/23 (0%) 0 3/32 (9.4%) 4
    Dermatitis Atopic 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 2/23 (8.7%) 3 1/32 (3.1%) 1
    Ecchymosis 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Granuloma Annulare 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Hyperkeratosis 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 0/41 (0%) 0 1/28 (3.6%) 1 0/34 (0%) 0 0/23 (0%) 0 1/32 (3.1%) 1
    Hypertrichosis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Lichen Planus 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Neurodermatitis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Pruritus 1/83 (1.2%) 1 0/82 (0%) 0 2/77 (2.6%) 2 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 1/73 (1.4%) 2 1/27 (3.7%) 1 1/41 (2.4%) 1 2/28 (7.1%) 2 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Psoriasis 1/83 (1.2%) 3 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 0/32 (0%) 0
    Rash Erythematous 1/83 (1.2%) 1 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 1/18 (5.6%) 1 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Rash Papular 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Sebaceous Hyperplasia 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 1/19 (5.3%) 1 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Skin Irritation 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Skin Lesion 1/83 (1.2%) 1 0/82 (0%) 0 3/77 (3.9%) 3 2/79 (2.5%) 3 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 1/27 (3.7%) 1 1/41 (2.4%) 2 0/28 (0%) 0 1/34 (2.9%) 1 0/23 (0%) 0 1/32 (3.1%) 1
    Urticaria 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 2/79 (2.5%) 2 0/78 (0%) 0 1/19 (5.3%) 3 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 1/41 (2.4%) 2 0/28 (0%) 0 1/34 (2.9%) 1 1/23 (4.3%) 2 0/32 (0%) 0
    Vascular disorders
    Hypertension 4/83 (4.8%) 4 7/82 (8.5%) 7 3/77 (3.9%) 3 8/79 (10.1%) 8 4/78 (5.1%) 4 0/19 (0%) 0 1/22 (4.5%) 1 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 2/19 (10.5%) 2 0/21 (0%) 0 2/18 (11.1%) 2 0/20 (0%) 0 5/73 (6.8%) 6 2/27 (7.4%) 2 2/41 (4.9%) 2 3/28 (10.7%) 3 6/34 (17.6%) 7 5/23 (21.7%) 5 3/32 (9.4%) 3
    Flushing 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 1 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Haematoma 0/83 (0%) 0 1/82 (1.2%) 1 0/77 (0%) 0 1/79 (1.3%) 1 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 1/17 (5.9%) 2 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 1/21 (4.8%) 1 0/18 (0%) 0 0/20 (0%) 0 2/73 (2.7%) 3 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 0/32 (0%) 0
    Phlebitis 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 0/79 (0%) 0 0/78 (0%) 0 0/19 (0%) 0 0/22 (0%) 0 1/18 (5.6%) 1 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 0/73 (0%) 0 0/27 (0%) 0 0/41 (0%) 0 0/28 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/32 (0%) 0
    Varicose Vein 0/83 (0%) 0 0/82 (0%) 0 0/77 (0%) 0 1/79 (1.3%) 2 0/78 (0%) 0 1/19 (5.3%) 1 0/22 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/18 (0%) 0 0/17 (0%) 0 0/19 (0%) 0 0/21 (0%) 0 0/18 (0%) 0 0/20 (0%) 0 1/73 (1.4%) 1 0/27 (0%) 0 2/41 (4.9%) 2 0/28 (0%) 0 0/34 (0%) 0 1/23 (4.3%) 1 1/32 (3.1%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00112437
    Other Study ID Numbers:
    • 0822-004
    • 2005_023
    First Posted:
    Jun 3, 2005
    Last Update Posted:
    Jan 24, 2018
    Last Verified:
    Dec 1, 2017