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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 135
- 主要终点
- Percent Change From Baseline to Month 12 in Femoral BMD
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Odanacatib 50 mg
Participants will receive odanacatib 50 mg once weekly for 24 months. Additionally, all participants will receive weekly supplementation with 5600 international units (IU) of Vitamin D3 and, if required, will be provided with an open-label daily calcium supplement of 500 mg (sourced locally as calcium carbonate or calcium citrate) to ensure a total daily intake (from both dietary and supplemental sources) of approximately 1200 mg of elemental calcium.
干预措施: odanacatib (Drug)
Placebo
Participants will receive dose-matched placebo to odanacatib once weekly for 24 months. Additionally, all participants will receive weekly supplementation with 5600 IU Vitamin D3 and, if required, will be provided with an open-label daily calcium supplement of 500 mg (sourced locally as calcium carbonate or calcium citrate) to ensure a total daily intake (from both dietary and supplemental sources) of approximately 1200 mg of elemental calcium.
干预措施: placebo to odanacatib (Other)
结局指标
主要结局
Percent Change From Baseline to Month 12 in Femoral BMD
时间窗: Baseline and Month 12
Dual-energy X-ray absorptiometry (DXA) was used to determine the change from baseline in femoral neck BMD at Month 12.
次要结局
- Percent Change From Baseline to Month 24 in Femoral Neck BMD: Within-Group Comparison of Odanacatib(Baseline and Month 24)
- Change From Baseline in Urine C-telopeptides of Type I Collagen (u-CTx)(Baseline and Month 12)
- Percent Change From Baseline to Month 12 in Trochanter, Total Hip, and Lumbar Spine BMD(Baseline and Month 12)
- Change From Baseline in Serum C-telopeptides of Type 1 Collagen (s-CTx)(Baseline and Month 12)
- Change From Baseline in Urine N-telopeptides of Type 1 Collagen Corrected for Creatinine (u-NTx/Cr)(Baseline and Month 12)
- Change From Baseline in Serum N-terminal Propeptide of Type 1 Collagen (s-P1NP)(Baseline and Month 12)
- Change From Baseline in Serum Bone Specific Alkaline Phosphatase (s-BSAP)(Baseline and Month 12)