Clinical Pharmacokinetics and Pharmacodynamics Study of Different Doses of Zoledronic Acid

June 21, 2021 updated by: Peking University Third Hospital

The Pharmacokinetics and Pharmacodynamics Study of Intravenous Zoledronic Acid in Chinese Subjects With Low Bone Mass or Osteoporosis: a Randomized Placebo-controlled Trail

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
64

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Zoledronic Acid Injection
Infusion 1mg zoledronic acid once.
Other Names:
  • Yigu
Drug: Zoledronic Acid Injection
Infusion 2.5mg zoledronic acid once.
Other Names:
  • Yigu
Drug: Zoledronic Acid Injection
Infusion 5mg zoledronic acid once.
Other Names:
  • Yigu
Experimental: 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.
Drug: Zoledronic Acid Injection
Infusion 1mg zoledronic acid once.
Other Names:
  • Yigu
Drug: Zoledronic Acid Injection
Infusion 2.5mg zoledronic acid once.
Other Names:
  • Yigu
Drug: Zoledronic Acid Injection
Infusion 5mg zoledronic acid once.
Other Names:
  • Yigu
Experimental: zoledronic acid 5mg
Infusion 100 mL of Zoledronic acid injection (100mL : 5mg) with constant speed in 20 minutes. Administration only once.
Drug: Zoledronic Acid Injection
Infusion 1mg zoledronic acid once.
Other Names:
  • Yigu
Drug: Zoledronic Acid Injection
Infusion 2.5mg zoledronic acid once.
Other Names:
  • Yigu
Drug: Zoledronic Acid Injection
Infusion 5mg zoledronic acid once.
Other Names:
  • Yigu
Placebo Comparator: placebo
Infusion 100 mL of normal saline with constant speed in 20 minutes. Administration only once.
Drug: Placebo
Infusion normal saline once.
Other Names:
  • Yigu Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Concentration of Zoledronic acid
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
Zoledronic acid concentration in plasma and urine.
Predose, 30 minutes, 2 hours, 24 hours, day 7, day 29, 3 months, 6 months, 12 months, 24 months, and 36 months post dose
Maximum concentration of Zoledronic acid
Time Frame: 0-36 months
The observed maximum concentration following administration (Cmax) in plasma after zoledronic acid infusion.
0-36 months
Time to reach maximum concentration of Zoledronic acid
Time Frame: 0-36 months
The time to reach the maximum concentration after administration (Tmax) in plasma after zoledronic acid infusion.
0-36 months
AUC of Zoledronic acid
Time Frame: 0-36 months
The area under the concentration-time curve (AUC) in plasma after zoledronic acid infusion.
0-36 months
terminal half-life of Zoledronic acid
Time Frame: 0-36 months
The terminal half-life (t1/2) of zoledronic acid after administration.
0-36 months
apparent clearance of Zoledronic acid
Time Frame: 0-36 months
The apparent clearance (CL/F) of zoledronic acid after administration.
0-36 months
apparent volume of distribution of Zoledronic acid
Time Frame: 0-36 months
The apparent volume of distribution of zoledronic acid after administration.
0-36 months
Concentration of bone turnover markers
Time Frame: 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.
0-36 months
Concentration of 25(OH)D and FGF23
Time Frame: 0-36 months
Concentration determination of 25(OH)D and fibroblast growth factor 23 (FGF23) with unit of ng/mL
0-36 months
PTH concentration determination
Time Frame: 0-36 months
Assessment of the profile of parathyroid hormone (PTH)
0-36 months
Serum sclerostin concentration determination
Time Frame: 0-36 months
Concentration-time profile of sclerostin (SOST) after zoledronic acid infusion.
0-36 months
Pharmacodynamic of zoledronic acid
Time Frame: 0-36 months
Assessment of lipid metabolism markers, such as low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol, and triglycerides.
0-36 months
Pharmacodynamic of zoledronic acid
Time Frame: 0-36 months
Assessment of fibroblast growth factor 19 (FGF19).
0-36 months
Pharmacodynamic of zoledronic acid
Time Frame: 0-36 months
Assessment of total bile acid.
0-36 months
Pharmacodynamic of zoledronic acid
Time Frame: 0-36 months
Assessment of bone mineral density at the lumbar spine, neck of femur, and total hip.
0-36 months
Change of immune indicator
Time Frame: 0-36 months
Changes in white blood cells(WBC)
0-36 months
Change of immune indicator
Time Frame: 0-36 months
Changes in C reaction protein (CRP)
0-36 months
Change of immune indicator
Time Frame: 0-36 months
Changes in interferon-γ (IFN-γ)
0-36 months
Change of immune indicator
Time Frame: 0-36 months
Changes in interleukin-6 (IL-6)
0-36 months
Change of immune indicator
Time Frame: 0-36 months
Changes in γδT cells activation
0-36 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of adverse event
Time Frame: 0-36 months
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.
0-36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking University Third Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 7, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 22, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 23, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 21, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • M2020427

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Drug Interventions

Conditions

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Drug Interventions

Dietary Supplements

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Locations

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