A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of MK-0822 (Cathepsin K Inhibitor) in the Treatment of Postmenopausal Women With Osteoporosis
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 399
- Primary Endpoint
- Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months
Overview
Brief Summary
This is a 1-year base study with a 1-year extension to examine the effects of a new experimental medication (odanacatib [MK-0822]) on postmenopausal osteoporosis. This study will enroll approximately 375 postmenopausal women, and randomly assign them to 4 different doses of odanacatib or to placebo. Measurements performed during the study include: bone mineral density scans, spine x-rays, laboratory blood and urine tests, height measurements and optional bone biopsies (at the end of 2 years).
Detailed Description
Study Extension:
Participants who completed 12 months of the base study and 12 months of the first extension were invited to continue in three additional extensions: MK0-822-004-10, which extended the study to 36 months, MK-0822-004-20 (NCT00112437) which extended the study to 60 months, and MK-0822-004-30 (NCT00112437), which extended the study to 120 months.
- In the first extension, participants continued to receive the same treatment they received in the 12-month base study.
- In the second extension, participants were re-randomized to odanacatib 50 mg OW or placebo OW for 12 months.
- In the third extension, participants who were initially randomized to odanacatib 3 mg or placebo OW in the base study received odanacatib 50 mg weekly in Years 4 and 5; all other participants remained on the same treatment they were during Year 3.
- In the fourth extension, all participants received odanacatib weekly in Years 6-10.
Study arms for extensions include only odanacatib 50 mg and placebo for the first two extensions and odanacatib 50 mg only for the third extension.
Extension Studies:
MK-0822-004-10 (NCT00112437) Extension: Participant has participated in and completed 24 months of treatment in the base study
MK-0822-004-20 (NCT00112437) Extension: Participant participated in and completed 36 months of treatment in base and extension studies.
MK-0822-004-30 (NCT00112437) Extension: Participant participated in and completed 60 months of treatment in the base and extension studies.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 45 Years to 85 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Postmenopausal for 5 or more years, defined as no menses for at least 5 years OR at least 5 years status post bilateral oophorectomy
- •Bone mineral density T-score at the hip or spine of -2.0 or less
- •Spinal anatomy suitable for dual-energy x-ray absorptiometry (DXA). At the lumbar spine, there is no evidence of vertebral fracture in at least 3 vertebrae in the L1 to L4 region on baseline spine films. (Significant scoliosis, bony trauma, degenerative joint disease, and sequelae of orthopedic procedures that result in anatomy that is unsuitable for accurate bone densitometry must be absent from the lumbar spine.)
- •At least one hip must be evaluable by DXA (e.g., contain no hardware from orthopedic procedures)
- •In a state of general health allowing for successful completion of the trial
- •Agreement to not use any medications to treat osteoporosis during the study
Exclusion Criteria
- •History of prior osteoporotic fracture (unless declined treatment with or was ineligible for osteoporosis therapy)
- •Past treatment with osteoporosis medications, steroids, hormone replacement, as well as various other medications that affect bone may be exclusionary. (Different exclusion criteria apply to each bone active drug. For example, any prior use of intravenous (IV) bisphosphonates is not permitted. By contrast, prior use of hormone replacement for several years is permitted if it has not occurred within the past 6 months. Please ask the study doctor for details)
- •Significant clinical or laboratory abnormalities at the screening visit for the study that, in the opinion of the investigator, could complicate interpretation of the study results or pose additional risk to the patient (for example, patients who are non-ambulatory should be excluded for this reason)
Arms & Interventions
Placebo
Intervention: Vitamin D3 (Dietary Supplement)
Odanacatib 50 mg
Intervention: Odanacatib (Drug)
Placebo
Intervention: Calcium Carbonate (Dietary Supplement)
Placebo
Intervention: Placebo (Drug)
Odanacatib 3 mg
Intervention: Odanacatib (Drug)
Odanacatib 3 mg
Intervention: Vitamin D3 (Dietary Supplement)
Odanacatib 3 mg
Intervention: Calcium Carbonate (Dietary Supplement)
Odanacatib 10 mg
Intervention: Odanacatib (Drug)
Odanacatib 10 mg
Intervention: Vitamin D3 (Dietary Supplement)
Odanacatib 10 mg
Intervention: Calcium Carbonate (Dietary Supplement)
Odanacatib 25 mg
Intervention: Odanacatib (Drug)
Odanacatib 25 mg
Intervention: Vitamin D3 (Dietary Supplement)
Odanacatib 25 mg
Intervention: Calcium Carbonate (Dietary Supplement)
Odanacatib 50 mg
Intervention: Vitamin D3 (Dietary Supplement)
Odanacatib 50 mg
Intervention: Calcium Carbonate (Dietary Supplement)
Outcomes
Primary Outcomes
Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months
Time Frame: Baseline and 12 months
Percentage change in lumbar spine BMD (relative to baseline) at 12 Months.
Percentage Change From Baseline in Lumbar Spine BMD at 24 Months
Time Frame: Baseline and 24 months
Percentage change in lumbar spine BMD (relative to baseline) at 24 Months.
Percentage Change From Baseline in Lumbar Spine BMD at 36 Months
Time Frame: Baseline and 36 months
Percentage change in lumbar spine BMD (relative to baseline) at 36 months
Percentage Change From Baseline in Lumbar Spine BMD at 60 Months
Time Frame: Baseline and Month 60
Percentage change from baseline in lumbar spine BMD at 60 months.
Percentage Change From Baseline in Lumbar Spine BMD at 120 Months
Time Frame: Baseline and Month 120
Percentage change from baseline in lumbar spine BMD at 120 Months.
Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment Years 6-10 (60 Months)
Time Frame: Years 6-10 (up to 60 months, up to 14 days after the last dose of study drug)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Years 6-10 (60 Months)
Time Frame: Years 6-10 (up to 60 months)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Secondary Outcomes
- Percentage Change From Baseline in Total Hip BMD at 12 Months(Baseline and 12 months)
- Percentage Change From Baseline in Trochanter BMD at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Total Body BMD at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Femoral Neck BMD at 12 Months(Baseline and 12 months)
- Percentage Change From Baseline in Total Body BMD at 12 Months(Baseline and 12 Months)
- Percentage Change From Baseline in Trochanter BMD at 12 Months(Baseline and 12 Months)
- Percentage Change From Baseline in Distal Forearm BMD at 12 Months(Baseline and 12 Months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 12 Months(Baseline and 12 Months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 12 Months(Baseline and 12 Months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 12 Months(Baseline and 12 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 12 Months(Baseline and 12 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 12 Months(Baseline and 12 months)
- Percentage Change From Baseline in Total Hip Bone Mineral Density at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Femoral Neck BMD at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Trochanter BMD at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Total Body BMD at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Distal Forearm BMD at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-Terminal Propeptide of Type 1 Collagen [s-P1NP]) at 24 Months(Baseline and 24 months)
- Percentage Change From Baseline in Total Hip BMD at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Femoral Neck BMD at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Distal Forearm BMD at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary N-Telopeptides of Type I Collagen [u-NTx]) at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum C-Telopeptides of Type 1 Collagen [s-CTx]) at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Urinary Total Deoxypyridinolines [u-DPyr]) at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone-specific Alkaline Phosphatase [s-BSAP]) at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum N-terminal Propeptide of Type 1 Collagen [s-P1NP]) at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b [TRAP 5-b]) at 36 Months(Baseline and 36 months)
- Percentage Change From Baseline in Biochemical Marker of Bone Turnover (Serum Cross-Linked Carboxyterminal Telopeptides of Type I Collagen [1-CTP]) at 36 Months(Baseline and 36 months)