AzTrials
AzTrials

Postmenopausal OsteoporosisPhase 4NCT04719650

Clinical Pharmacokinetics and Pharmacodynamics Study of Different Doses of Zoledronic Acid

A Phase 4 study testing Zoledronic Acid Injection in people with Postmenopausal Osteoporosis, run by Peking University Third Hospital.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 60 to 70 years, women onlyHealthy volunteers can take part
Conditions the study is for
Postmenopausal Osteoporosis
What is being tested?
Zoledronic Acid Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
64 participants
Where
No sites listed yet
Study dates
Oct 2021to Nov 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 70 years
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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:
  • intravenous biphosphonates or denosumab. (2) oral biphosphonates, parathyroid hormone or its analogues, strontium, or fluoride within 12 months.
  • 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.
Show all 19Show fewer
  • 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 locations and contacts

No sites are listed yet.

Qi Liu, Ph. D. contact

+8615501060136

liuqicpu@hotmail.com

About this study

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

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.

Being tested
Zoledronic Acid Injection, Placebo
Keywords
zoledronic acid, pharmacokinetic, pharmacodynamic, Chinese osteoporosis
Medical subject headings
Osteoporosis, Postmenopausal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Zoledronic Acid InjectionDrug

    Also called Yigu

    Infusion 1mg zoledronic acid once.

  • Zoledronic Acid InjectionDrug

    Also called Yigu

    Infusion 2.5mg zoledronic acid once.

  • Zoledronic Acid InjectionDrug

    Also called Yigu

    Infusion 5mg zoledronic acid once.

  • PlaceboDrug

    Also called Yigu Placebo

    Infusion normal saline once.

Study groups in NCT04719650
Study groupRoleWhat they receive
zoledronic acid 1mgExperimentalAdd 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.
Receives: Drug: Zoledronic Acid Injection
zoledronic acid 2.5mgExperimentalAdd 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.
Receives: Drug: Zoledronic Acid Injection
zoledronic acid 5mgExperimentalInfusion 100 mL of Zoledronic acid injection (100mL : 5mg) with constant speed in 20 minutes. Administration only once.
Receives: Drug: Zoledronic Acid Injection
placeboPlacebo comparatorInfusion 100 mL of normal saline with constant speed in 20 minutes. Administration only once.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Concentration of Zoledronic acid

    Zoledronic acid concentration in plasma and urine.

    Measured: Predose, 30 minutes, 2 hours, 24 hours, day 7, day 29, 3 months, 6 months, 12 months, 24 months, and 36 months post dose

  2. Maximum concentration of Zoledronic acid

    The observed maximum concentration following administration (Cmax) in plasma after zoledronic acid infusion.

    Measured: 0-36 months

  3. Time to reach maximum concentration of Zoledronic acid

    The time to reach the maximum concentration after administration (Tmax) in plasma after zoledronic acid infusion.

    Measured: 0-36 months

  4. AUC of Zoledronic acid

    The area under the concentration-time curve (AUC) in plasma after zoledronic acid infusion.

    Measured: 0-36 months

  5. terminal half-life of Zoledronic acid

    The terminal half-life (t1/2) of zoledronic acid after administration.

    Measured: 0-36 months

  6. apparent clearance of Zoledronic acid

    The apparent clearance (CL/F) of zoledronic acid after administration.

    Measured: 0-36 months

  7. apparent volume of distribution of Zoledronic acid

    The apparent volume of distribution of zoledronic acid after administration.

    Measured: 0-36 months

  8. 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.

    Measured: 0-36 months

  9. Concentration of 25(OH)D and FGF23

    Concentration determination of 25(OH)D and fibroblast growth factor 23 (FGF23) with unit of ng/mL

    Measured: 0-36 months

  10. PTH concentration determination

    Assessment of the profile of parathyroid hormone (PTH)

    Measured: 0-36 months

  11. Serum sclerostin concentration determination

    Concentration-time profile of sclerostin (SOST) after zoledronic acid infusion.

    Measured: 0-36 months

  12. Pharmacodynamic of zoledronic acid

    Assessment of lipid metabolism markers, such as low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol, and triglycerides.

    Measured: 0-36 months

  13. Pharmacodynamic of zoledronic acid

    Assessment of fibroblast growth factor 19 (FGF19).

    Measured: 0-36 months

  14. Pharmacodynamic of zoledronic acid

    Assessment of total bile acid.

    Measured: 0-36 months

  15. Pharmacodynamic of zoledronic acid

    Assessment of bone mineral density at the lumbar spine, neck of femur, and total hip.

    Measured: 0-36 months

  16. Change of immune indicator

    Changes in white blood cells(WBC)

    Measured: 0-36 months

  17. Change of immune indicator

    Changes in C reaction protein (CRP)

    Measured: 0-36 months

  18. Change of immune indicator

    Changes in interferon-γ (IFN-γ)

    Measured: 0-36 months

  19. Change of immune indicator

    Changes in interleukin-6 (IL-6)

    Measured: 0-36 months

  20. Change of immune indicator

    Changes in γδT cells activation

    Measured: 0-36 months

Secondary outcomes (1)

  1. 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.

    Measured: 0-36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jan 2021
  2. Study startOct 2021 (estimated)
  3. Primary completionOct 2024 (estimated)
  4. Study completionNov 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
64 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04719650
Sponsor's protocol ID
M2020427
Status last verified
Jan 2021
First submitted
7 Jan 2021
Last updated
23 Jun 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 25182228

  • 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.

    PubMed 12730746

  • 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.

    PubMed 28960821

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Zoledronic Acid Injection in people with Postmenopausal Osteoporosis, run by Peking University Third Hospital.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 23 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Qi Liu, Ph. D. (+8615501060136, liuqicpu@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04719650, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in