Clinical trial NCT00529373: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Postmenopausal Osteoporosis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-09-14
Enrollment: 16071
Sex: FEMALE
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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) .


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

Primary outcomes:
measure: Base Study: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)
timeFrame: Up to approximately 60 months of observation
measure: Base Study + First Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Hip Fracture (Adjudicated)
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Non-Vertebral Fracture (Adjudicated)
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Rate of Adverse Events
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Rate of Discontinuations From Study Treatment Due to an Adverse Event
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension + Second Extension: Percent Change From Baseline in Bone Mineral Density (BMD) Measurements of the Total Hip
timeFrame: Baseline and once yearly, up to approximately 108 months of observation
measure: Second Extension: Number of Participants Who Experienced an Adverse Event
timeFrame: Up to approximately 34 months of observation
measure: Second Extension: Number of Participants Discontinuing Study Treatment Due to an Adverse Event
timeFrame: Up to approximately 34 months of observation
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in Volumetric Bone Mineral Density (vBMD) at the Lumbar Spine Using Quantitative Computed Tomography
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in vBMD at the Lumbar Spine Using Quantitative Computed Tomography
timeFrame: Baseline, Month 60
measure: Sarcopenia Substudy PN035: Change From Baseline in Appendicular Lean Body Mass (aLBM)
timeFrame: Baseline and once yearly up to 4 years
measure: Sarcopenia Substudy PN035: Change From Baseline in Short Physical Performance Battery (SPPB) Score
timeFrame: Baseline and once yearly up to 4 years
measure: Sarcopenia Substudy PN035: Change From Baseline in Gait Speed
timeFrame: Baseline and once yearly up to 4 years.
Secondary outcomes:
measure: Base Study: Rate of Adverse Events
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Rate of Discontinuation From Study Treatment Due to an Adverse Event
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Yearly Rate of Height Loss
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Number of Participants With Height Loss of > 1 cm
timeFrame: Baseline and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip
timeFrame: Baseline, Month 6, and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine
timeFrame: Baseline, Month 6, and once yearly, approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck
timeFrame: Baseline, Month 6, and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter
timeFrame: Baseline, Month 6, and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm
timeFrame: Baseline and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Lumbar Spine in Bisphosphonate-Intolerant Participants
timeFrame: Baseline, Month 6, and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Total Hip in Bisphosphonate-Intolerant Participants
timeFrame: Baseline, Month 6, and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Femoral Neck in Bisphosphonate-Intolerant Participants
timeFrame: Baseline, Month 6, and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Trochanter in Bisphosphonate-Intolerant Participants
timeFrame: Baseline, Month 6, and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm in Bisphosphonate-Intolerant Participants
timeFrame: Baseline and once yearly, up to approximately 60 months of observation
measure: Base Study: Percent Change From Baseline in Serum C-Telopeptides of Type I Collagen (s-CTx) After Log-Transformation
timeFrame: Baseline, Month 6, and once yearly up to 4 years
measure: Base Study: Percent Change From Baseline in Urinary N-Telopeptides of Type I Collagen/Creatinine (u-NTx/Cr) Ratio After Log-Transformation
timeFrame: Baseline, Month 6, and once yearly up to 4 years
measure: Base Study: Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) After Log-Transformation
timeFrame: Baseline, Month 6, and once yearly up to 4 years
measure: Base Study: Percent Change From Baseline in N-Terminal Propeptide of Type 1 Collagen (P1NP) After Log-Transformation
timeFrame: Baseline, Month 6, and once yearly up to 4 years
measure: Base Study: Time to First 3-Point Major Adverse Cardiac Event (MACE) Confirmed by Thrombolysis in Myocardial Infarction Study Group (TIMI) Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First 4-Point MACE Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First All-Cause Death Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First Cardiovascular Death Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study: Time to First Fatal Stroke Confirmed by TIMI Adjudication
timeFrame: Up to approximately 60 months of observation
measure: Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck
timeFrame: Baseline, Month 6, and once yearly, up to approximately 74 months of observation
measure: Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Distal-Third Forearm
timeFrame: Baseline and once yearly, up to approximately 74 months of observation
measure: Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Vertebral Fracture (Adjudicated)
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time From Baseline to First Osteoporotic Clinical Fracture (Adjudicated)
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Total Hip
timeFrame: Baseline, Month 6, and once yearly, up to approximately 74 months of observation
measure: Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Trochanter
timeFrame: Baseline, Month 6, and once yearly, up to approximately 74 months of observation
measure: Base Study + First Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine
timeFrame: Baseline, Month 6, and once yearly, up to approximately 74 months of observation
measure: Base Study + First Extension + Second Extension: Time From Baseline to First Morphometrically-Assessed Vertebral Fracture
timeFrame: Up to approximately 108 months of observation
measure: Base Study + First Extension + Second Extension: Change in Height From Baseline Stature
timeFrame: Baseline and once yearly, up to approximately 108 months of observation
measure: Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Lumbar Spine
timeFrame: Baseline and once yearly, up to approximately 108 months of observation
measure: Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Femoral Neck
timeFrame: Baseline and once yearly, up to approximately 108 months of observation
measure: Base Study + First Extension + Second Extension: Percent Change From Baseline in BMD Measurements of the Trochanter
timeFrame: Baseline and once yearly, up to approximately 108 months of observation
measure: Second Extension: Incidence of Osteoporotic Clinical Lumbar Vertebral Fracture (Adjudicated)
timeFrame: Up to approximately 34 months of observation
measure: Second Extension: Incidence of Osteoporotic Clinical Thoracic Vertebral Fracture (Adjudicated)
timeFrame: Up to approximately 34 months of observation
measure: Second Extension: Time From Baseline to First Osteoporotic Clinical Fracture of Any Type (Adjudicated)
timeFrame: Up to approximately 34 months of observation
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in Areal BMD (aBMD) of the Lumbar Spine Using DXA
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Total Hip Using DXA
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Trochanter Using DXA
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in s-CTx After Log-Transformation
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in P1NP After Log-Transformation
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in aBMD of the Distal-Third Forearm Using DXA
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in BSAP After Log-Transformation
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base: Percent Change From Baseline in u-NTx/Cr Ratio After Log-Transformation
timeFrame: Baseline, Month 24
measure: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in Cortical vBMD of the Total Hip Using Quantitative Computed Tomography
timeFrame: Baseline, Month 60
measure: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Lumbar Spine Using DXA
timeFrame: Baseline, Month 60
measure: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Total Hip Using DXA
timeFrame: Baseline, Month 60
measure: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Femoral Neck Using DXA
timeFrame: Baseline, Month 60
measure: Imaging Substudy PN032-Base + Extension: Percent Change From Baseline in aBMD of the Trochanter Using DXA
timeFrame: Baseline, Month 60
Other outcomes:
measure: Base Study + First Extension: Time to First Hospitalization for Unstable Angina Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First Cardiovascular Death Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First Fatal Myocardial Infarction Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First 3-Point MACE Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First All-Cause Death Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First New Onset ECG-Confirmed Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First Fatal or Non-Fatal Myocardial Infarction Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First Fatal or Non-Fatal Stroke Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First Any Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First Fatal Stroke Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First 4-Point MACE Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
measure: Base Study + First Extension: Time to First New Onset Atrial Fibrillation or Atrial Flutter Confirmed by TIMI Adjudication
timeFrame: Up to approximately 74 months of observation
Locations:
Study officials:
References:
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.
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.
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.
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.
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.