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A Study of MK-0822 in Postmenopausal Women With Osteoporosis to Assess Fracture Risk (MK-0822-018)

Primary Purpose

Postmenopausal Osteoporosis

Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Odanacatib
Placebo for Odanacatib
Vitamin D3
Calcium carbonate
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postmenopausal Osteoporosis

Eligibility Criteria

65 Years - undefined (Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Postmenopausal women (for at least 5 years) who are ≥65 years of age and have low bone mineral density
  • Ambulatory (able to walk)

Exclusion Criteria:

  • Must not be taking osteoporosis therapy or have a metabolic bone disorder other than osteoporosis
  • Has or has had a hip fracture
  • Currently participating in another drug study

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Odanacatib

    Placebo

    Arm Description

    Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly for 5 years. Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly for 5 years. Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.

    Outcomes

    Primary Outcome Measures

    Base Study: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
    Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant semiquantitative [SQ] Grade 1-3) (T4 to L4) were confirmed by quantitative morphometric (QM) and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).
    Base Study: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)
    Osteoporotic clinical hip fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Base Study: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)
    Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Base Study + First Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
    Morphometric vertebral fractures were confirmed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant SQ Grade 1-3) (T4 to L4) were confirmed by QM and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).
    Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)
    Osteoporotic clinical hip fractures was confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)
    Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur and shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Base Study + First Extension: Rate of Adverse Events
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 person-years of follow-up) is provided.
    Base Study + First Extension: Rate of Discontinuations From Study Treatment Due to an Adverse Event
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 person-years of follow-up) is provided.
    Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip
    BMD was measured by dual-energy x-ray absorptiometry (DXA) at the total hip starting at screening, and at yearly intervals until the end of the study (second extension study) for all participants who entered the second extension study. Least squares (LS) means percent change in BMD from original baseline are provided through Month 108 (Year 9). At Months 96 (Year 8) and 108 (Year 9), approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study.
    Second Extension: Number of Participants Who Experienced an Adverse Event
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
    Second Extension: Number of Participants Discontinuing Study Treatment Due to an Adverse Event
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
    Imaging Substudy PN032-Base: Percent Change From Baseline in Volumetric Bone Mineral Density (vBMD) at the Lumbar Spine Using Quantitative Computed Tomography
    Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 24 (base study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in vBMD at the Lumbar Spine Using Quantitative Computed Tomography
    Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Sarcopenia Substudy PN035: Change From Baseline in Appendicular Lean Body Mass (aLBM)
    Sarcopenia is the age-related loss of skeletal muscle mass and associated loss of strength. Progression of sarcopenia was assessed using aLBM as measured by total body DXA. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Sarcopenia Substudy PN035: Change From Baseline in Short Physical Performance Battery (SPPB) Score
    The Short Physical Performance Battery (SPPB) Score is used to assess physical function in older persons. The SPPB consists of 3 types of physical activities: standing balance, gait speed, and chair rise. Component activities are timed and then reduced to a categorical 0 to 4 scale based on time achieved. A higher composite score (range 0 to 12) indicates an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Sarcopenia Substudy PN035: Change From Baseline in Gait Speed
    Gait speed is a component of the Short Physical Performance Battery (SPPB) Score. Participants are asked to walk a distance of 4 meters at their normal pace. The test is performed 2 times, and the walk done in the shortest time is used for scoring. The activity is timed and then reduced to a categorical 0 to 4 scale based on time achieved. Higher scores indicate an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

    Secondary Outcome Measures

    Base Study: Rate of Adverse Events
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 person-years of follow-up) is provided.
    Base Study: Rate of Discontinuation From Study Treatment Due to an Adverse Event
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 person-years of follow-up) is provided.
    Base Study: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Base Study: Yearly Rate of Height Loss
    Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study.
    Base Study: Number of Participants With Height Loss of > 1 cm
    Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study.
    Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip
    BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study).
    Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine
    BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. at
    Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck
    BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study).
    Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter
    BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study).
    Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm
    BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study) in an approximate 10% random subset of participants at selected sites.
    Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants
    BMD was measured by DXA in bisphosphonate-intolerant participants at the lumbar spine at randomization, and at yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants
    BMD was measured by DXA in bisphosphonate-intolerant participants at the total hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants
    BMD was measured by DXA in bisphosphonate-intolerant participants at the femoral neck-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants
    BMD was measured by DXA in bisphosphonate-intolerant participants at the trochanter-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants
    BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study) in an approximate 10% random subset of bisphosphonate-intolerant participants at selected sites. Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation
    s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation
    u-NTx, a biochemical marker of bone resorption, was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. Urine NTx measurements (in bone collagen equivalents [BCE]) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) and the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation
    BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation
    P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Base Study: Time to First 3-Point Major Adverse Cardiac Event (MACE) Confirmed by Thrombolysis in Myocardial Infarction Study Group (TIMI) Adjudication
    The time to first TIMI-adjudicated 3-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, or 3. non-fatal definite stroke) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First 4-Point MACE Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated 4-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, 3. non-fatal definite stroke, or 4. hospitalization for unstable angina) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated hospitalization for unstable angina was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated any reported episode of atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were included and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First All-Cause Death Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated all-cause death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First Cardiovascular Death Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated cardiovascular death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated fatal or non-fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated fatal or non-fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study: Time to First Fatal Stroke Confirmed by TIMI Adjudication
    The time to first TIMI-adjudicated fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck
    BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp).
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm
    BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study + first extension-dbp) in an approximate 10% random subset of participants at selected sites.
    Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Fracture (Adjudicated)
    Osteoporotic clinical fractures (combining vertebral and non-vertebral) were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Total Hip
    BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp).
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Trochanter
    BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp).
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine
    BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses.
    Base Study + First Extension + Second Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
    Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline (base study) and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant semiquantitative [SQ] Grade 1-3) (T4 to L4) were confirmed by quantitative morphometric (QM) and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).
    Base Study + First Extension + Second Extension: Change in Height From Baseline Stature
    Height was measured by wall-mounted stadiometer at randomization and at yearly intervals across the base study and the two extension studies.
    Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine
    BMD was measured by DXA at the lumbar spine starting at randomization, and at yearly intervals until the end of the study (2nd extension study) for all participants who entered the 2nd extension study. Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. At Months 96 and 108, approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study. A longitudinal model with terms for treatment, stratum, region & interaction between treatment and time as fixed effects (LS means weighted for region & stratum size) was used for analysis.
    Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck
    BMD was measured by DXA at the femoral neck starting at screening, and at yearly intervals until the end of the study (2nd extension study) for all participants who entered the 2nd extension study. LS means percent change in BMD from original baseline are provided through Month 108. At Months 96 and 108, approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study. A longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size) was used for analysis.
    Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter
    BMD was measured by DXA at the trochanter starting at screening, and at yearly intervals until the end of the study (2nd extension study) for all participants who entered the 2nd extension study. LS means percent change in BMD from original baseline are provided through Month 108. At Months 96 and 108, approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study. A longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size) was used for analysis.
    Second Extension: Incidence of Osteoporotic Clinical Lumbar Vertebral Fracture (Adjudicated)
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all lumbar vertebral levels (L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second extension study with osteoporotic vertebral clinical fractures is provided. Due to early termination of the study, the cumulative incidence using a time-to-event methodology was not assessed across base and extension studies.
    Second Extension: Incidence of Osteoporotic Clinical Thoracic Vertebral Fracture (Adjudicated)
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all thoracic vertebral levels (T1 to T12). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second extension study with osteoporotic vertebral clinical fractures is provided. Due to early termination of the study, the cumulative incidence using a time-to-event methodology was not assessed across base and extension studies.
    Second Extension: Time From Baseline to First Osteoporotic Clinical Fracture of Any Type (Adjudicated)
    Osteoporotic clinical fractures of any type were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist; Vertebral fractures assessed across all vertebral levels (C7, T1 to T12, L1 to L5) were included in the analysis. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence proportion (cumulative incidence) of participants in the second extension study with at least one osteoporotic clinical fracture of any type is provided.
    Imaging Substudy PN032-Base: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography
    Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 24 was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base: Percent Change From Baseline in Areal BMD (aBMD) of the Lumbar Spine Using DXA
    aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 24 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA
    aBMD was measured at the femoral neck at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Total Hip Using DXA
    aBMD was measured at the total hip at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Trochanter Using DXA
    aBMD was measured at the trochanter at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base: Percent Change From Baseline in s-CTx After Log-Transformation
    s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Imaging Substudy PN032-Base: Percent Change From Baseline in P1NP After Log-Transformation
    P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction change from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Distal-Third Forearm Using DXA
    aBMD was measured at the the distal one-third radius at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base: Percent Change From Baseline in BSAP After Log-Transformation
    BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Imaging Substudy PN032-Base: Percent Change From Baseline in u-NTx/Cr Ratio After Log-Transformation
    u-NTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. Urine NTx measurements (in BCE) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) and the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography
    Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Lumbar Spine Using DXA
    aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 60 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Total Hip Using DXA
    aBMD was measured at the total hip at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA
    aBMD was measured at the femoral neck at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Trochanter Using DXA
    aBMD was measured at the trochanter at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).

    Full Information

    First Posted
    September 12, 2007
    Last Updated
    October 23, 2019
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00529373
    Brief Title
    A Study of MK-0822 in Postmenopausal Women With Osteoporosis to Assess Fracture Risk (MK-0822-018)
    Official Title
    A Phase III Randomized, Placebo-Controlled Clinical Trial to Assess the Safety and Efficacy of Odanacatib (MK-0822) to Reduce the Risk of Fracture in Osteoporotic Postmenopausal Women Treated With Vitamin D and Calcium
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2019
    Overall Recruitment Status
    Terminated
    Study Start Date
    September 13, 2007 (Actual)
    Primary Completion Date
    November 14, 2012 (Actual)
    Study Completion Date
    February 1, 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of the event-driven base study is to determine the safety and efficacy, especially fracture risk reduction, of odanacatib in postmenopausal women diagnosed with osteoporosis. In a placebo-controlled extension of the base study, participants continued to receive the same blinded study medication for a total of up to 5 years of blinded study medication combined between the base study and the extension. After participants received 5 years of blinded study medication, they received open-label odanacatib through the end of the first extension. Participants were then invited to enroll in a second extension study in which they received open-label odanacatib for an additional 5 years. Two imaging substudies (PN032-Base/Extension and PN035) were conducted for participants in the MK-0822-018 Study. Additional safety information was collected for participants who discontinued from the base study or the blinded first extension in an observational follow-up study, MK-0822-083 (EudraCT number: 2007-002693-66) .

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Postmenopausal Osteoporosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    16071 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Odanacatib
    Arm Type
    Experimental
    Arm Description
    Participants receive 50 mg of blinded odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly for 5 years. Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants receive blinded placebo to 50 mg of odanacatib weekly over the course of the base study and first extension study (5 years total), followed by 50 mg of open-label odanacatib weekly for 5 years. Participants also receive Vitamin D3 and open-label supplemental calcium so that total daily calcium intake (from both dietary and supplemental sources) is approximately 1200 mg.
    Intervention Type
    Drug
    Intervention Name(s)
    Odanacatib
    Other Intervention Name(s)
    MK-0822
    Intervention Description
    50 mg tablet orally once weekly (OW)
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo for Odanacatib
    Intervention Description
    50 mg tablet orally OW
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Vitamin D3
    Intervention Description
    5600 IU orally OW
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Calcium carbonate
    Other Intervention Name(s)
    Calcium supplements
    Intervention Description
    If needed. Total daily calcium intake (from both dietary and supplemental sources) will be approximately 1200 mg but not to exceed 1600 mg
    Primary Outcome Measure Information:
    Title
    Base Study: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
    Description
    Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant semiquantitative [SQ] Grade 1-3) (T4 to L4) were confirmed by quantitative morphometric (QM) and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)
    Description
    Osteoporotic clinical hip fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)
    Description
    Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study + First Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
    Description
    Morphometric vertebral fractures were confirmed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant SQ Grade 1-3) (T4 to L4) were confirmed by QM and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)
    Description
    Osteoporotic clinical hip fractures was confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Hip fractures were fractures of the proximal femur confirmed as being located in the hip (i.e., sub-region not specified; cervical, and intertrochanteric). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)
    Description
    Osteoporotic non-vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur and shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Rate of Adverse Events
    Description
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Rate of Discontinuations From Study Treatment Due to an Adverse Event
    Description
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip
    Description
    BMD was measured by dual-energy x-ray absorptiometry (DXA) at the total hip starting at screening, and at yearly intervals until the end of the study (second extension study) for all participants who entered the second extension study. Least squares (LS) means percent change in BMD from original baseline are provided through Month 108 (Year 9). At Months 96 (Year 8) and 108 (Year 9), approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study.
    Time Frame
    Baseline and once yearly, up to approximately 108 months of observation
    Title
    Second Extension: Number of Participants Who Experienced an Adverse Event
    Description
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
    Time Frame
    Up to approximately 34 months of observation
    Title
    Second Extension: Number of Participants Discontinuing Study Treatment Due to an Adverse Event
    Description
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
    Time Frame
    Up to approximately 34 months of observation
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in Volumetric Bone Mineral Density (vBMD) at the Lumbar Spine Using Quantitative Computed Tomography
    Description
    Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 24 (base study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in vBMD at the Lumbar Spine Using Quantitative Computed Tomography
    Description
    Compartment-specific effects of osteoporosis were assessed by measuring trabecular vBMD at the lumbar spine (L1 total vertebral body) using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 60
    Title
    Sarcopenia Substudy PN035: Change From Baseline in Appendicular Lean Body Mass (aLBM)
    Description
    Sarcopenia is the age-related loss of skeletal muscle mass and associated loss of strength. Progression of sarcopenia was assessed using aLBM as measured by total body DXA. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline and once yearly up to 4 years
    Title
    Sarcopenia Substudy PN035: Change From Baseline in Short Physical Performance Battery (SPPB) Score
    Description
    The Short Physical Performance Battery (SPPB) Score is used to assess physical function in older persons. The SPPB consists of 3 types of physical activities: standing balance, gait speed, and chair rise. Component activities are timed and then reduced to a categorical 0 to 4 scale based on time achieved. A higher composite score (range 0 to 12) indicates an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline and once yearly up to 4 years
    Title
    Sarcopenia Substudy PN035: Change From Baseline in Gait Speed
    Description
    Gait speed is a component of the Short Physical Performance Battery (SPPB) Score. Participants are asked to walk a distance of 4 meters at their normal pace. The test is performed 2 times, and the walk done in the shortest time is used for scoring. The activity is timed and then reduced to a categorical 0 to 4 scale based on time achieved. Higher scores indicate an improved function level. The change from baseline at yearly intervals was then assessed using a longitudinal data analysis model with terms for treatment, stratum (sarcopenia, non-sarcopenia), time and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline and once yearly up to 4 years.
    Secondary Outcome Measure Information:
    Title
    Base Study: Rate of Adverse Events
    Description
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participants with adverse events (number of participants with an event per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Rate of Discontinuation From Study Treatment Due to an Adverse Event
    Description
    An adverse event is defined as any untoward medical occurrence in a person or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The incidence rate of participant discontinuations from treatment due to adverse events (number of participants with an event per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)
    Description
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Yearly Rate of Height Loss
    Description
    Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Number of Participants With Height Loss of > 1 cm
    Description
    Height was measured by wall-mounted stadiometer at randomization and at yearly intervals in the base study.
    Time Frame
    Baseline and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip
    Description
    BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study).
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine
    Description
    BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. at
    Time Frame
    Baseline, Month 6, and once yearly, approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck
    Description
    BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study).
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter
    Description
    BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study).
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm
    Description
    BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study) in an approximate 10% random subset of participants at selected sites.
    Time Frame
    Baseline and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants
    Description
    BMD was measured by DXA in bisphosphonate-intolerant participants at the lumbar spine at randomization, and at yearly intervals until the end of the study (base study). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants
    Description
    BMD was measured by DXA in bisphosphonate-intolerant participants at the total hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants
    Description
    BMD was measured by DXA in bisphosphonate-intolerant participants at the femoral neck-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants
    Description
    BMD was measured by DXA in bisphosphonate-intolerant participants at the trochanter-hip at screening, and at yearly intervals until the end of the study (base study). Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants
    Description
    BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study) in an approximate 10% random subset of bisphosphonate-intolerant participants at selected sites. Bisphosphonates are anti-resorptive agents used in the treatment of osteoporosis. Bisphosphonate-intolerance was defined by contraindication or history of intolerance to bisphosphonates, or physician's determination of unsuitability for bisphosphonate treatment.
    Time Frame
    Baseline and once yearly, up to approximately 60 months of observation
    Title
    Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation
    Description
    s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Time Frame
    Baseline, Month 6, and once yearly up to 4 years
    Title
    Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation
    Description
    u-NTx, a biochemical marker of bone resorption, was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. Urine NTx measurements (in bone collagen equivalents [BCE]) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) and the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Time Frame
    Baseline, Month 6, and once yearly up to 4 years
    Title
    Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation
    Description
    BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Time Frame
    Baseline, Month 6, and once yearly up to 4 years
    Title
    Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation
    Description
    P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at randomization, Month 6, and at yearly intervals until the end of the study (base study) in an approximate 10% random subset participants at selected sites. The log-transformed fraction from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Time Frame
    Baseline, Month 6, and once yearly up to 4 years
    Title
    Base Study: Time to First 3-Point Major Adverse Cardiac Event (MACE) Confirmed by Thrombolysis in Myocardial Infarction Study Group (TIMI) Adjudication
    Description
    The time to first TIMI-adjudicated 3-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, or 3. non-fatal definite stroke) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First 4-Point MACE Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated 4-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, 3. non-fatal definite stroke, or 4. hospitalization for unstable angina) was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated hospitalization for unstable angina was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated any reported episode of atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were included and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First All-Cause Death Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated all-cause death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First Cardiovascular Death Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated cardiovascular death was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated fatal or non-fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated fatal definite myocardial infarction was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated fatal or non-fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study: Time to First Fatal Stroke Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated fatal definite stroke was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 60 months of observation
    Title
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck
    Description
    BMD was measured by DXA for all participants at the femoral neck-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp).
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 74 months of observation
    Title
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm
    Description
    BMD was measured by DXA at the distal one-third radius at randomization and at yearly intervals until the end of the study (base study + first extension-dbp) in an approximate 10% random subset of participants at selected sites.
    Time Frame
    Baseline and once yearly, up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)
    Description
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Fracture (Adjudicated)
    Description
    Osteoporotic clinical fractures (combining vertebral and non-vertebral) were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all vertebral levels (C7, T1 to T12, L1 to L5). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence rate of participants with fracture (number of participants with a fracture per 100 person-years of follow-up) is provided.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Total Hip
    Description
    BMD was measured by DXA for all participants at the total hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp).
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 74 months of observation
    Title
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Trochanter
    Description
    BMD was measured by DXA for all participants at the trochanter-hip at screening, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp).
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 74 months of observation
    Title
    Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine
    Description
    BMD was measured by DXA for all participants at the lumbar spine at randomization, Months 6, 12, and subsequent yearly intervals until the end of the study (base study + first extension-dbp). Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses.
    Time Frame
    Baseline, Month 6, and once yearly, up to approximately 74 months of observation
    Title
    Base Study + First Extension + Second Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
    Description
    Morphometric vertebral fractures were assessed by central adjudication on lumbar and thoracic spinal radiographs acquired at baseline (base study) and at Months 6, 12, and subsequent yearly time points. Incident fractures (i.e., occurring after baseline) in previously normal vertebral bodies and/or those occurring after baseline in previously fractured vertebral bodies (Genant semiquantitative [SQ] Grade 1-3) (T4 to L4) were confirmed by quantitative morphometric (QM) and either SQ or binary SQ (yes/no) methodologies. A time-to-event methodology was used to evaluate results: life-table estimates of the incidence proportion (cumulative incidence) of participants with at least one morphometric vertebral fracture were assessed at Months 6, 12, and subsequent yearly intervals; an interval-censored approach was then used to determine incidence rate (number of participants with a morphometric fracture per 100 person-years of follow-up).
    Time Frame
    Up to approximately 108 months of observation
    Title
    Base Study + First Extension + Second Extension: Change in Height From Baseline Stature
    Description
    Height was measured by wall-mounted stadiometer at randomization and at yearly intervals across the base study and the two extension studies.
    Time Frame
    Baseline and once yearly, up to approximately 108 months of observation
    Title
    Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine
    Description
    BMD was measured by DXA at the lumbar spine starting at randomization, and at yearly intervals until the end of the study (2nd extension study) for all participants who entered the 2nd extension study. Measurements were made on at least 3 vertebrae for all time points; vertebrae with fractures were excluded from analyses. At Months 96 and 108, approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study. A longitudinal model with terms for treatment, stratum, region & interaction between treatment and time as fixed effects (LS means weighted for region & stratum size) was used for analysis.
    Time Frame
    Baseline and once yearly, up to approximately 108 months of observation
    Title
    Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck
    Description
    BMD was measured by DXA at the femoral neck starting at screening, and at yearly intervals until the end of the study (2nd extension study) for all participants who entered the 2nd extension study. LS means percent change in BMD from original baseline are provided through Month 108. At Months 96 and 108, approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study. A longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size) was used for analysis.
    Time Frame
    Baseline and once yearly, up to approximately 108 months of observation
    Title
    Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter
    Description
    BMD was measured by DXA at the trochanter starting at screening, and at yearly intervals until the end of the study (2nd extension study) for all participants who entered the 2nd extension study. LS means percent change in BMD from original baseline are provided through Month 108. At Months 96 and 108, approximately 3% or fewer participants in each treatment group had BMD data, and results at those time points should be viewed with caution. NOTE: The mean percent change in BMD from baseline in participants originally randomized to placebo includes BMD results obtained after those participants were switched to open-label odanacatib, which occurred at different times relative to their start of blinded study medication in the base study. A longitudinal model with terms for treatment, stratum, region and interaction between treatment and time as fixed effects (LS means weighted for region and stratum size) was used for analysis.
    Time Frame
    Baseline and once yearly, up to approximately 108 months of observation
    Title
    Second Extension: Incidence of Osteoporotic Clinical Lumbar Vertebral Fracture (Adjudicated)
    Description
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all lumbar vertebral levels (L1 to L5). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second extension study with osteoporotic vertebral clinical fractures is provided. Due to early termination of the study, the cumulative incidence using a time-to-event methodology was not assessed across base and extension studies.
    Time Frame
    Up to approximately 34 months of observation
    Title
    Second Extension: Incidence of Osteoporotic Clinical Thoracic Vertebral Fracture (Adjudicated)
    Description
    Osteoporotic vertebral clinical fractures were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Vertebral fractures were assessed for all thoracic vertebral levels (T1 to T12). Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence of participants in the second extension study with osteoporotic vertebral clinical fractures is provided. Due to early termination of the study, the cumulative incidence using a time-to-event methodology was not assessed across base and extension studies.
    Time Frame
    Up to approximately 34 months of observation
    Title
    Second Extension: Time From Baseline to First Osteoporotic Clinical Fracture of Any Type (Adjudicated)
    Description
    Osteoporotic clinical fractures of any type were confirmed by central adjudication using radiographic evidence on all symptomatic fractures reported as adverse experiences (excluding fractures of the fingers, toes, face, and skull). Non-vertebral fractures were assessed across multiple anatomical sites including clavicle, distal femur or shaft, fibula, hip, humerus, pelvis, radius, ribs, sacrum, tibia, ulna, and wrist; Vertebral fractures assessed across all vertebral levels (C7, T1 to T12, L1 to L5) were included in the analysis. Osteoporotic (fragility) fractures did not include fractures with traumatic or pathological etiologies. A clinical fracture was defined as a fracture with clinical fracture-related symptoms (e.g., pain). A time-to-event methodology was used to evaluate results: the incidence proportion (cumulative incidence) of participants in the second extension study with at least one osteoporotic clinical fracture of any type is provided.
    Time Frame
    Up to approximately 34 months of observation
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography
    Description
    Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 24 was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in Areal BMD (aBMD) of the Lumbar Spine Using DXA
    Description
    aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 24 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA
    Description
    aBMD was measured at the femoral neck at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Total Hip Using DXA
    Description
    aBMD was measured at the total hip at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Trochanter Using DXA
    Description
    aBMD was measured at the trochanter at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in s-CTx After Log-Transformation
    Description
    s-CTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in s-CTx was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in P1NP After Log-Transformation
    Description
    P1NP is a cleavage fragment produced during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum P1NP was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction change from baseline in P1NP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Distal-Third Forearm Using DXA
    Description
    aBMD was measured at the the distal one-third radius at baseline and Month 24 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in BSAP After Log-Transformation
    Description
    BSAP is an enzyme produced by matrix-synthesizing osteoblasts during the synthesis of collagenous bone matrix (type 1 collagen) used as a biochemical marker of bone formation. Serum BSAP was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. The log-transformed fraction from baseline in BSAP was determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base: Percent Change From Baseline in u-NTx/Cr Ratio After Log-Transformation
    Description
    u-NTx, a biochemical marker of bone resorption by osteoclasts reflecting collagen breakdown products, was assessed at baseline and Month 24 in an approximate 10% random subset participants at selected sites in the P018 base study who were additionally included in the imaging substudy PN032-base study. Urine NTx measurements (in BCE) were normalized to urine Cr concentration (i.e., u-NTx/Cr ratio) and the log-transformed fraction from baseline in u-NTx/Cr ratio was then determined using a longitudinal model with terms for treatment, stratum, and interaction between treatment and time as fixed effects (LS means weighted for stratum size). Back-transformed weighted geometric LS means values for percent change from baseline are provided.
    Time Frame
    Baseline, Month 24
    Title
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography
    Description
    Compartment-specific effects of osteoporosis were assessed by measuring cortical vBMD at the total hip using quantitative computed tomography. The percent change from baseline at Month 60 (base study + extension study) was then assessed using a longitudinal data analysis model including terms for treatment, stratum (prior vertebral fracture [yes/no]) and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 60
    Title
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Lumbar Spine Using DXA
    Description
    aBMD was measured at the lumbar spine (L1 to L4) at baseline and Month 60 using DXA . If a vertebra was fractured at baseline or became fractured during the study, its BMD measurement was excluded from analysis. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 60
    Title
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Total Hip Using DXA
    Description
    aBMD was measured at the total hip at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 60
    Title
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA
    Description
    aBMD was measured at the femoral neck at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 60
    Title
    Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Trochanter Using DXA
    Description
    aBMD was measured at the trochanter at baseline and Month 60 using DXA. The percent change from baseline was assessed using a longitudinal data analysis model including terms for treatment, stratum and interaction between treatment and time as fixed effects (LS means weighted for stratum size).
    Time Frame
    Baseline, Month 60
    Other Pre-specified Outcome Measures:
    Title
    Base Study + First Extension: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated hospitalization for unstable angina was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First Cardiovascular Death Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated cardiovascular death was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated fatal definite myocardial infarction was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First 3-Point MACE Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated 3-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, or 3. non-fatal definite stroke) was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First All-Cause Death Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated all-cause death was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. The analysis includes data obtained from vital status data collections of participants no longer followed in the base study. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated fatal or non-fatal definite myocardial infarction was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated fatal or non-fatal definite stroke was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated any reported episode of atrial fibrillation or atrial flutter was determined for the base study using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were included and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First Fatal Stroke Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated fatal definite stroke was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First 4-Point MACE Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated 4-point MACE (a composite outcome measure of 1. cardiovascular death, 2. non-fatal definite MI, 3. non-fatal definite stroke, or 4. hospitalization for unstable angina) was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation
    Title
    Base Study + First Extension: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
    Description
    The time to first TIMI-adjudicated new or presumed new onset atrial fibrillation or atrial flutter was determined for the base study + first extension using a Cox proportional hazards model with terms for treatment, stratum and geographic region. Participants with known history of atrial fibrillation or atrial flutter were excluded and electrocardiogram confirmation was not required. Results are expressed as number of participants with an event per 100 person-years of follow-up. Results from MK-0822-083, a follow up study to the MK-088-018 base study and the double-blind period of the first extension study for participants who discontinued prior to 5 years follow-up, are not included.
    Time Frame
    Up to approximately 74 months of observation

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Postmenopausal women (for at least 5 years) who are ≥65 years of age and have low bone mineral density Ambulatory (able to walk) Exclusion Criteria: Must not be taking osteoporosis therapy or have a metabolic bone disorder other than osteoporosis Has or has had a hip fracture Currently participating in another drug study

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    25432773
    Citation
    Bone HG, Dempster DW, Eisman JA, Greenspan SL, McClung MR, Nakamura T, Papapoulos S, Shih WJ, Rybak-Feiglin A, Santora AC, Verbruggen N, Leung AT, Lombardi A. Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the Long-Term Odanacatib Fracture Trial. Osteoporos Int. 2015 Feb;26(2):699-712. doi: 10.1007/s00198-014-2944-6. Epub 2014 Nov 29. Erratum In: Osteoporos Int. 2015 Nov;26(11):2721.
    Results Reference
    background
    PubMed Identifier
    35711006
    Citation
    Duong LT, Clark S, Pickarski M, Giezek H, Cohn D, Massaad R, Stoch SA. Effects of odanacatib on bone-turnover markers in osteoporotic postmenopausal women: a post hoc analysis of the LOFT study. Osteoporos Int. 2022 Oct;33(10):2165-2175. doi: 10.1007/s00198-022-06406-x. Epub 2022 Jun 17.
    Results Reference
    derived
    PubMed Identifier
    33724542
    Citation
    Papapoulos S, Bone H, Cosman F, Dempster DW, McClung MR, Nakamura T, Restrepo JFM, Bouxsein ML, Cohn D, de Papp A, Massaad R, Santora A. Incidence of Hip and Subtrochanteric/Femoral Shaft Fractures in Postmenopausal Women With Osteoporosis in the Phase 3 Long-Term Odanacatib Fracture Trial. J Bone Miner Res. 2021 Jul;36(7):1225-1234. doi: 10.1002/jbmr.4284. Epub 2021 Apr 27.
    Results Reference
    derived
    PubMed Identifier
    32119749
    Citation
    Recker R, Dempster D, Langdahl B, Giezek H, Clark S, Ellis G, de Villiers T, Valter I, Zerbini CA, Cohn D, Santora A, Duong LT. Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women With Osteoporosis: 5-Year Data From the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT) and its Extension. J Bone Miner Res. 2020 Jul;35(7):1289-1299. doi: 10.1002/jbmr.3994. Epub 2020 May 5.
    Results Reference
    derived
    PubMed Identifier
    31676222
    Citation
    McClung MR, O'Donoghue ML, Papapoulos SE, Bone H, Langdahl B, Saag KG, Reid IR, Kiel DP, Cavallari I, Bonaca MP, Wiviott SD, de Villiers T, Ling X, Lippuner K, Nakamura T, Reginster JY, Rodriguez-Portales JA, Roux C, Zanchetta J, Zerbini CAF, Park JG, Im K, Cange A, Grip LT, Heyden N, DaSilva C, Cohn D, Massaad R, Scott BB, Verbruggen N, Gurner D, Miller DL, Blair ML, Polis AB, Stoch SA, Santora A, Lombardi A, Leung AT, Kaufman KD, Sabatine MS; LOFT Investigators. Odanacatib for the treatment of postmenopausal osteoporosis: results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study. Lancet Diabetes Endocrinol. 2019 Dec;7(12):899-911. doi: 10.1016/S2213-8587(19)30346-8. Epub 2019 Oct 31.
    Results Reference
    derived

    Learn more about this trial

    A Study of MK-0822 in Postmenopausal Women With Osteoporosis to Assess Fracture Risk (MK-0822-018)

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