Back to resultsClinical Pharmacokinetics and Pharmacodynamics Study of Different Doses of Zoledronic Acid
Primary Purpose
Postmenopausal Osteoporosis
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Zoledronic Acid Injection
Zoledronic Acid Injection
Zoledronic Acid Injection
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Postmenopausal Osteoporosis focused on measuring zoledronic acid, pharmacokinetic, pharmacodynamic, Chinese osteoporosis
Eligibility Criteria
Inclusion Criteria:
- Chinese postmenopausal women
- Aged between 60 and 70.
- Bone mineral density (BMD) values of less than 1 standard deviations (SD) below the normal adult mean.
- Willing to participate in this study.
Exclusion Criteria:
- 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.
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
zoledronic acid 1mg
zoledronic acid 2.5mg
zoledronic acid 5mg
placebo
Arm 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.
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.
Infusion 100 mL of Zoledronic acid injection (100mL : 5mg) with constant speed in 20 minutes. Administration only once.
Infusion 100 mL of normal saline with constant speed in 20 minutes. Administration only once.
Outcomes
Primary Outcome Measures
Concentration of Zoledronic acid
Zoledronic acid concentration in plasma and urine.
Maximum concentration of Zoledronic acid
The observed maximum concentration following administration (Cmax) in plasma after zoledronic acid infusion.
Time to reach maximum concentration of Zoledronic acid
The time to reach the maximum concentration after administration (Tmax) in plasma after zoledronic acid infusion.
AUC of Zoledronic acid
The area under the concentration-time curve (AUC) in plasma after zoledronic acid infusion.
terminal half-life of Zoledronic acid
The terminal half-life (t1/2) of zoledronic acid after administration.
apparent clearance of Zoledronic acid
The apparent clearance (CL/F) of zoledronic acid after administration.
apparent volume of distribution of Zoledronic acid
The apparent volume of distribution of zoledronic acid after administration.
Concentration of bone turnover markers
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
Concentration determination of 25(OH)D and fibroblast growth factor 23 (FGF23) with unit of ng/mL
PTH concentration determination
Assessment of the profile of parathyroid hormone (PTH)
Serum sclerostin concentration determination
Concentration-time profile of sclerostin (SOST) after zoledronic acid infusion.
Pharmacodynamic of zoledronic acid
Assessment of lipid metabolism markers, such as low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol, and triglycerides.
Pharmacodynamic of zoledronic acid
Assessment of fibroblast growth factor 19 (FGF19).
Pharmacodynamic of zoledronic acid
Assessment of total bile acid.
Pharmacodynamic of zoledronic acid
Assessment of bone mineral density at the lumbar spine, neck of femur, and total hip.
Change of immune indicator
Changes in white blood cells(WBC)
Change of immune indicator
Changes in C reaction protein (CRP)
Change of immune indicator
Changes in interferon-γ (IFN-γ)
Change of immune indicator
Changes in interleukin-6 (IL-6)
Change of immune indicator
Changes in γδT cells activation
Secondary Outcome Measures
Incidence of adverse event
The occurrence time and severity of fracture. The occurrence time and severity of acute phase response. The occurrence time and severity of other adverse event.
Full Information
NCT ID
NCT04719650
First Posted
January 7, 2021
Last Updated
June 21, 2021
Sponsor
Peking University Third Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04719650
Brief Title
Clinical Pharmacokinetics and Pharmacodynamics Study of Different Doses of Zoledronic Acid
Official Title
The Pharmacokinetics and Pharmacodynamics Study of Intravenous Zoledronic Acid in Chinese Subjects With Low Bone Mass or Osteoporosis: a Randomized Placebo-controlled Trail
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2021 (Anticipated)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University Third Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postmenopausal Osteoporosis
Keywords
zoledronic acid, pharmacokinetic, pharmacodynamic, Chinese osteoporosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
64 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
zoledronic acid 1mg
Arm Type
Experimental
Arm 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.
Arm Title
zoledronic acid 2.5mg
Arm Type
Experimental
Arm 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.
Arm Title
zoledronic acid 5mg
Arm Type
Experimental
Arm Description
Infusion 100 mL of Zoledronic acid injection (100mL : 5mg) with constant speed in 20 minutes. Administration only once.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Infusion 100 mL of normal saline with constant speed in 20 minutes. Administration only once.
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid Injection
Other Intervention Name(s)
Yigu
Intervention Description
Infusion 1mg zoledronic acid once.
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid Injection
Other Intervention Name(s)
Yigu
Intervention Description
Infusion 2.5mg zoledronic acid once.
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid Injection
Other Intervention Name(s)
Yigu
Intervention Description
Infusion 5mg zoledronic acid once.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Yigu Placebo
Intervention Description
Infusion normal saline once.
Primary Outcome Measure Information:
Title
Concentration of Zoledronic acid
Description
Zoledronic acid concentration in plasma and urine.
Time Frame
Predose, 30 minutes, 2 hours, 24 hours, day 7, day 29, 3 months, 6 months, 12 months, 24 months, and 36 months post dose
Title
Maximum concentration of Zoledronic acid
Description
The observed maximum concentration following administration (Cmax) in plasma after zoledronic acid infusion.
Time Frame
0-36 months
Title
Time to reach maximum concentration of Zoledronic acid
Description
The time to reach the maximum concentration after administration (Tmax) in plasma after zoledronic acid infusion.
Time Frame
0-36 months
Title
AUC of Zoledronic acid
Description
The area under the concentration-time curve (AUC) in plasma after zoledronic acid infusion.
Time Frame
0-36 months
Title
terminal half-life of Zoledronic acid
Description
The terminal half-life (t1/2) of zoledronic acid after administration.
Time Frame
0-36 months
Title
apparent clearance of Zoledronic acid
Description
The apparent clearance (CL/F) of zoledronic acid after administration.
Time Frame
0-36 months
Title
apparent volume of distribution of Zoledronic acid
Description
The apparent volume of distribution of zoledronic acid after administration.
Time Frame
0-36 months
Title
Concentration of bone turnover markers
Description
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.
Time Frame
0-36 months
Title
Concentration of 25(OH)D and FGF23
Description
Concentration determination of 25(OH)D and fibroblast growth factor 23 (FGF23) with unit of ng/mL
Time Frame
0-36 months
Title
PTH concentration determination
Description
Assessment of the profile of parathyroid hormone (PTH)
Time Frame
0-36 months
Title
Serum sclerostin concentration determination
Description
Concentration-time profile of sclerostin (SOST) after zoledronic acid infusion.
Time Frame
0-36 months
Title
Pharmacodynamic of zoledronic acid
Description
Assessment of lipid metabolism markers, such as low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol, and triglycerides.
Time Frame
0-36 months
Title
Pharmacodynamic of zoledronic acid
Description
Assessment of fibroblast growth factor 19 (FGF19).
Time Frame
0-36 months
Title
Pharmacodynamic of zoledronic acid
Description
Assessment of total bile acid.
Time Frame
0-36 months
Title
Pharmacodynamic of zoledronic acid
Description
Assessment of bone mineral density at the lumbar spine, neck of femur, and total hip.
Time Frame
0-36 months
Title
Change of immune indicator
Description
Changes in white blood cells(WBC)
Time Frame
0-36 months
Title
Change of immune indicator
Description
Changes in C reaction protein (CRP)
Time Frame
0-36 months
Title
Change of immune indicator
Description
Changes in interferon-γ (IFN-γ)
Time Frame
0-36 months
Title
Change of immune indicator
Description
Changes in interleukin-6 (IL-6)
Time Frame
0-36 months
Title
Change of immune indicator
Description
Changes in γδT cells activation
Time Frame
0-36 months
Secondary Outcome Measure Information:
Title
Incidence of adverse event
Description
The occurrence time and severity of fracture. The occurrence time and severity of acute phase response. The occurrence time and severity of other adverse event.
Time Frame
0-36 months
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Chinese postmenopausal women
Aged between 60 and 70.
Bone mineral density (BMD) values of less than 1 standard deviations (SD) below the normal adult mean.
Willing to participate in this study.
Exclusion Criteria:
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.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qi Liu, Ph. D.
Phone
+8615501060136
Email
liuqicpu@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chunli Song, M.D.; Ph. D.
Organizational Affiliation
Peking University Third Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25182228
Citation
Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R; National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014 Oct;25(10):2359-81. doi: 10.1007/s00198-014-2794-2. Epub 2014 Aug 15. Erratum In: Osteoporos Int. 2015 Jul;26(7):2045-7.
Results Reference
background
PubMed Identifier
12730746
Citation
Shiraki M, Fukunaga M, Kushida K, Kishimoto H, Taketani Y, Minaguchi H, Inoue T, Morita R, Morii H, Yamamoto K, Ohashi Y, Orimo H. A double-blind dose-ranging study of risedronate in Japanese patients with osteoporosis (a study by the Risedronate Late Phase II Research Group). Osteoporos Int. 2003 May;14(3):225-34. doi: 10.1007/s00198-002-1369-9. Epub 2003 Apr 10.
Results Reference
background
PubMed Identifier
28960821
Citation
Ding Y, Zeng JC, Yin F, Zhang CL, Zhang Y, Li SX, Liu X, Zhang C, Xue QY, Lin H, Pei FX. Multicenter Study on Observation of Acute-phase Responses After Infusion of Zoledronic Acid 5 mg in Chinese Women with Postmenopausal Osteoporosis. Orthop Surg. 2017 Aug;9(3):284-289. doi: 10.1111/os.12338.
Results Reference
background
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Clinical Pharmacokinetics and Pharmacodynamics Study of Different Doses of Zoledronic Acid
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