Clinical Pharmacokinetics and Pharmacodynamics Study of Different Doses of Zoledronic Acid

Peking University

Status and phase: Not yet enrolling; Phase 4

Conditions: Postmenopausal Osteoporosis

Treatments: Drug: Zoledronic Acid Injection; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04719650

M2020427

Details and patient eligibility

About

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.

Enrollment: 64 estimated patients

Sex: Female

Ages: 60 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Chinese postmenopausal women
2. Aged between 60 and 70.
3. Bone mineral density (BMD) values of less than 1 standard deviations (SD) below the normal adult mean.
4. Willing to participate in this study.

Exclusion criteria

1. Hypersensitivity to zoledronic acid or other bisphosphonate or zoledronic acid formulation (excipients).
2. Secondary osteoporosis.
3. 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.

4. 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.

5. Hyperthyroidism or hypothyroidism during screening.

6. Treatment with any investigational drug within the past 3 months.

7. Creatinine clearance < 35 mL/min.

8. 25(OH)D level< 20 ng/mL.

9. Serum calcium level < 2.0 mmol/L (8 mg/dL), or >2.8 mmol/L (11.0 mg/dL).

10. Fever, severe infections, severe injuries, or major surgical operation within 30 days.

11. ECG corrected QT interval (QTc) > 480 ms.

12. Pending invasive dental procedure or in progress.

13. History of smoking within 6 months.

14. Diabetes with fasting blood glucose ≥ 7.0 mmol/L, or glycated hemoglobin (HbA1c) >6.3%.

15. History of drug or alcohol abuse.

16. History of stroke, cerebral ischemic stroke, or cerebral hemorrhage.

17. Any physiological or medical condition which, in the opinion of the investigator, would preclude the participant from this trail.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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64 participants in 4 patient groups, including a placebo group

zoledronic acid 1mg

Experimental group

Description:

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.

Treatment:

Drug: Zoledronic Acid Injection

Drug: Zoledronic Acid Injection

Drug: Zoledronic Acid Injection

zoledronic acid 2.5mg

Experimental group

Description:

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.

Treatment:

Drug: Zoledronic Acid Injection

Drug: Zoledronic Acid Injection

Drug: Zoledronic Acid Injection

zoledronic acid 5mg

Experimental group

Description:

Infusion 100 mL of Zoledronic acid injection (100mL : 5mg) with constant speed in 20 minutes. Administration only once.

Treatment:

Drug: Zoledronic Acid Injection

Drug: Zoledronic Acid Injection

Drug: Zoledronic Acid Injection

placebo

Placebo Comparator group

Description:

Infusion 100 mL of normal saline with constant speed in 20 minutes. Administration only once.

Treatment:

Drug: Placebo