Clinical trial NCT01803607: Efficacy and Safety of Odanacatib in Postmenopausal Women Previously Treated With Oral Bisphosphonate (MK-0822-076)
Official title: A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Odanacatib (MK-0822) on Bone Mineral Density (BMD) and Overall Safety in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Osteoporosis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-03-04
Enrollment: 135
Sex: FEMALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess to what extent sequential treatment with odanacatib results in incremental gains in bone mineral density (BMD) over time in female participants who have received at least 3 years of bisphosphonate therapy. It was hypothesized that odanacatib treatment would increase femoral neck BMD relative to placebo after 24 months.


Eligibility criteria: Inclusion Criteria:

* Postmenopausal for ≥5 years (defined as no menses for at least 5 years or at least 5 years post bilateral oophorectomy).
* Prior or current treatment with oral bisphosphonate therapy (i.e., alendronate, risedronate, ibandronate) for postmenopausal osteoporosis for ≥3 years.
* BMD T-score at any hip site (femoral neck, trochanter, or total hip) ≤-2.5 and \>-3.5 as assessed by dual-energy X-ray absorptiometry (DXA) without a history of a prior fragility fracture. For participants with a history of a prior fragility fracture (except hip fracture), BMD T-score can be ≤-1.5 and \>-3.5 at any hip site.
* Serum 25-hydroxyvitamin D level of ≥20 and ≤60 ng/mL within 90 days of the time of randomization.

Exclusion Criteria:

* Evidence of a metabolic bone disorder other than osteopenia or osteoporosis
* History or current evidence of hip fracture.
* History of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
* Active parathyroid disease. Participant with a documented history of parathyroid disease can be considered for inclusion if she has normal parathyroid hormone (PTH) at screening.
* History of thyroid disease not adequately controlled by medication.
* Current treatment with anti-seizure medication, with indices of calcium metabolism not within normal limits.
* Prior treatment with strontium-containing products; intravenous bisphosphonates; cathepsin K inhibitors; RANK ligand inhibitors; fluoride treatment at a dose greater than 1 mg/day for more than 2 weeks.
* Use of following medications within the 6 months prior to the screening visit: activated vitamin D; estrogen, with or without progestin, at a dose high enough to have systemic effects; raloxifene or other selective estrogen receptor modulator (SERM), tibolone or any aromatase inhibitor; sub-cutaneous calcitonin (Note: use of intranasal calcitonin is allowed at any time); anabolic steroid; PTH (1-34 or 1-84); growth hormone; systemic glucocorticoids (≥5 mg/day of prednisone or equivalent) for more than 2 weeks; cyclosporine for more than 2 weeks.
* Concurrent use of cancer chemotherapy or heparin; protease inhibitors for human immunodeficiency virus (HIV) treatment; and vitamin A (excluding beta carotene) \>10,000 IU daily, unless willing to discontinue this dose during the study.
* Current treatment with cytochrome P450 3A4 (CYP3A4) inducers or treatment with CYP3A4 inducer within 4 weeks of screening.

Primary outcomes:
measure: Percent Change From Baseline to Month 12 in Femoral BMD
timeFrame: Baseline and Month 12
Secondary outcomes:
measure: Percent Change From Baseline to Month 24 in Femoral Neck BMD: Within-Group Comparison of Odanacatib
timeFrame: Baseline and Month 24
measure: Percent Change From Baseline to Month 12 in Trochanter, Total Hip, and Lumbar Spine BMD
timeFrame: Baseline and Month 12
measure: Change From Baseline in Serum C-telopeptides of Type 1 Collagen (s-CTx)
timeFrame: Baseline and Month 12
measure: Change From Baseline in Urine C-telopeptides of Type I Collagen (u-CTx)
timeFrame: Baseline and Month 12
measure: Change From Baseline in Urine N-telopeptides of Type 1 Collagen Corrected for Creatinine (u-NTx/Cr)
timeFrame: Baseline and Month 12
measure: Change From Baseline in Serum Bone Specific Alkaline Phosphatase (s-BSAP)
timeFrame: Baseline and Month 12
measure: Change From Baseline in Serum N-terminal Propeptide of Type 1 Collagen (s-P1NP)
timeFrame: Baseline and Month 12
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: