The Pharmacokinetics and Pharmacodynamics Study of Intravenous Zoledronic Acid in Chinese Subjects With Low Bone Mass or Osteoporosis: a Randomized Placebo-controlled Trail
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 64
- 主要终点
- Concentration of Zoledronic acid
研究概览
简要总结
The recommended dosing regimen of zoledronic acid in Chinese osteoporosis patients is completely in accordance with the one of 5 mg per year abroad that based on the dosing regimen in Paget's disease. This dosing regimen lacks the actual supportive clinical data of Chinese patients. In addition, the overall incidence of acute phase response, the main adverse event after the first infusion, in Chinese patients is higher than that in Caucasian patients population. Moreover, the results of the similar drug clinical study in the Japanese patients shown that the purpose of effective treatment for osteoporosis could be achieved with half of the dosage in Caucasian population. Thus, it could be inferred from these that the dosing regimen of zoledronic acid might be inappropriate in Chinese osteoporosis patients. Therefore, the main purpose of this clinical trail is to compare the zoledronic acid pharmacokinetic and pharmacodynamic characteristic of different doses in Chinese postmenopausal subjects with low bone mass or osteoporosis and explore the best dosing regimen in Chinese patients.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Chinese postmenopausal women
- •Aged between 60 and
- •Bone mineral density (BMD) values of less than 1 standard deviations (SD) below the normal adult mean.
- •Willing to participate in this study.
排除标准
- •Hypersensitivity to zoledronic acid or other bisphosphonate or zoledronic acid formulation (excipients).
- •Secondary osteoporosis.
- •Receiving the following drugs that affect bone metabolism prior to randomization:
- •(1) intravenous biphosphonates or denosumab. (2) oral biphosphonates, parathyroid hormone or its analogues, strontium, or fluoride within 12 months.
- •(3) glucocorticoid, steroids, immunosuppressive agents, calcitonin, calcitriol or its analogues, thiazides diuretics, long-acting estrogen/progesterone, or statins within 3 months.
- •Combine other diseases affect bone metabolism: osteogenesis imperfecta, hyperthyroidism, malignant tumors, Paget's disease, rheumatoid arthritis, osteomalacia, osteopetrosis, ankylosing spondylitis, liver failure, or renal failure.
- •Hyperthyroidism or hypothyroidism during screening.
- •Treatment with any investigational drug within the past 3 months.
- •Creatinine clearance < 35 mL/min.
- •25(OH)D level< 20 ng/mL.
- •Serum calcium level < 2.0 mmol/L (8 mg/dL), or >2.8 mmol/L (11.0 mg/dL).
- •Fever, severe infections, severe injuries, or major surgical operation within 30 days.
- •ECG corrected QT interval (QTc) > 480 ms.
- •Pending invasive dental procedure or in progress.
- •History of smoking within 6 months.
- •Diabetes with fasting blood glucose ≥ 7.0 mmol/L, or glycated hemoglobin (HbA1c) >6.3%.
- •History of drug or alcohol abuse.
- •History of stroke, cerebral ischemic stroke, or cerebral hemorrhage.
- •Any physiological or medical condition which, in the opinion of the investigator, would preclude the participant from this trail.
研究组 & 干预措施
zoledronic acid 1mg
Add 20 mL of Zoledronic acid injection (100mL : 5mg) with 80 mL of normal saline to 100 mL. Infusion 20 minutes with constant speed. Administration only once.
干预措施: Zoledronic Acid Injection (Drug)
zoledronic acid 2.5mg
Add 50 mL of Zoledronic acid injection (100mL : 5mg) with 50 mL of normal saline to 100 mL. Infusion 20 minutes with constant speed. Administration only once.
干预措施: Zoledronic Acid Injection (Drug)
zoledronic acid 5mg
Infusion 100 mL of Zoledronic acid injection (100mL : 5mg) with constant speed in 20 minutes. Administration only once.
干预措施: Zoledronic Acid Injection (Drug)
placebo
Infusion 100 mL of normal saline with constant speed in 20 minutes. Administration only once.
干预措施: Placebo (Drug)
结局指标
主要结局
Concentration of Zoledronic acid
时间窗: Predose, 30 minutes, 2 hours, 24 hours, day 7, day 29, 3 months, 6 months, 12 months, 24 months, and 36 months post dose
Zoledronic acid concentration in plasma and urine.
AUC of Zoledronic acid
时间窗: 0-36 months
The area under the concentration-time curve (AUC) in plasma after zoledronic acid infusion.
apparent clearance of Zoledronic acid
时间窗: 0-36 months
The apparent clearance (CL/F) of zoledronic acid after administration.
Maximum concentration of Zoledronic acid
时间窗: 0-36 months
The observed maximum concentration following administration (Cmax) in plasma after zoledronic acid infusion.
Time to reach maximum concentration of Zoledronic acid
时间窗: 0-36 months
The time to reach the maximum concentration after administration (Tmax) in plasma after zoledronic acid infusion.
Concentration of bone turnover markers
时间窗: 0-36 months
Concentration-time profile of procollagen type 1 N-propeptide (P1NP), bone-specific alkaline phosphatase (ALP), osteocalcin (OCN), C-telopeptide (CTx), and tartrate-resistant acid phosphatase 5b (TRACP-5b) with unit of ng/mL.
Concentration of 25(OH)D and FGF23
时间窗: 0-36 months
Concentration determination of 25(OH)D and fibroblast growth factor 23 (FGF23) with unit of ng/mL
PTH concentration determination
时间窗: 0-36 months
Assessment of the profile of parathyroid hormone (PTH)
apparent volume of distribution of Zoledronic acid
时间窗: 0-36 months
The apparent volume of distribution of zoledronic acid after administration.
terminal half-life of Zoledronic acid
时间窗: 0-36 months
The terminal half-life (t1/2) of zoledronic acid after administration.
Serum sclerostin concentration determination
时间窗: 0-36 months
Concentration-time profile of sclerostin (SOST) after zoledronic acid infusion.
Pharmacodynamic of zoledronic acid
时间窗: 0-36 months
Assessment of bone mineral density at the lumbar spine, neck of femur, and total hip.
Change of immune indicator
时间窗: 0-36 months
Changes in γδT cells activation
次要结局
- Incidence of adverse event(0-36 months)