Pharmacokinetics, Pharmacodynamics and Safety of LY01005 in Patients With Prostate Cancer Compared to ZOLADEX®

May 15, 2023 updated by: Luye Pharma Group Ltd.

A Randomized, Open-label and Parallel Phase I Study to Compare Pharmacokinetics, Pharmacodynamics and Safety of Goserelin Acetate Sustained-Release Microspheres for Injection (LY01005) and ZOLADEX® Following Multiple Administration in Patients With Prostate Cancer

This is a randomized, open-label and parallel phase I study to compare pharmacokinetics (PK), pharmacodynamics (PD) and safety of goserelin acetate sustained-release microspheres for injection (LY01005) and ZOLADEX® following multiple administration in patients with prostate cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

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.

Detailed Description

This is a randomized, open-label, active-controlled phase I trial. A total of 23 patients with locally advanced or metastatic prostate cancer who were suitable for endocrine therapy were enrolled into the screening period from D-21 to D-10 (±3d) before administration. Eligible subjects were treated with bicalutamide tablets (Casodex®, 50 mg/day) from D-10 (± 3d) to the end of the trial and randomized in a 1:1 ratio to receive LY01005 3.6 mg or ZOLADEX ® 3.6 mg after completion of pretreatment. All subjects were administered once every 28 days for three doses. Blood samples were collected at the specified time points in the trial protocol to detect PK parameters of goserelin, and PD parameters (serum testosterone, LH and FSH). Safety evaluation (including vital signs, physical examination, laboratory tests, 12 ECG, adverse events, etc.) was conducted as required in the protocol. This study aimed to compare PK/PD and safety of LY01005 and ZOLADEX® in patients with locally advanced or metastatic prostate cancer.

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 (Actual)

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.
23

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 1

Contacts and Locations

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

Study Locations

  • China
      • Guangzhou, China
        • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 years or older.
  • Patients with locally advanced or metastatic prostate cancer suitable for endocrine therapy, including those who are suitable for endocrine therapy (such as patients with biochemical recurrence after adjuvant endocrine therapy and radical therapy) following radical therapy.
  • Serum testosterone level ≥ 150 ng/dL (1.50 ng/mL or 5.2 nmol/L) at the screening visit.
  • Life expectancy of at least 9 months.
  • ECOG score of ≤ 2.
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelet count ≥ 90 x 10^9/L, white blood cell count ≥ 3 x 10^9/L, hemoglobin ≥ 90 g/L, total bilirubin (TBIL) ≤ 1.5×ULN, ALT and AST ≤ 2.5×ULN (or ≤ 5.0×ULN for patients with liver metastases), and Creatinine clearance ≥50 mL/min at the screening visit.
  • Subjects of childbearing potential must agree to use a reliable method of contraception with their female sexual partners during the study period and at least 3 months after the last administration.
  • Patients who voluntarily sign an IRB-approved informed consent form before any trial-related activities, are willing to abide by the restrictions of the study, and complete the prescribed examinations.

Exclusion Criteria:

  • Patients with prostate cancer who receive previous or ongoing endocrine therapy (surgical castration or other endocrine therapy including GnRH receptor agonists, GnRH receptor antagonists, anti-androgens, estrogens, megestrol acetate, etc.), except for patients with prostate cancer undergoing prostatectomy, radiotherapy or cryotherapy who have received neoadjuvant/adjuvant endocrine therapy for no more than 6 months and discontinued the above therapy more than 6 months before screening.
  • Patients with confirmed or suspected hormone-resistant prostate cancer.
  • Patients who have received prostatic surgery within 4 weeks prior to the first dose, or plan to receive major surgical treatment during the trial.
  • Patients who have previously received hypophysectomy or adrenalectomy, or who have pituitary lesions or adrenal dysfunction.
  • History of severe asthma, anaphylaxis, or severe urticaria and/or angioedema.
  • Other cancer diseases diagnosed within 5 years before the screening visit, except for surgically removed basal or squamous cell carcinoma of the skin.
  • History of the following medical histories within 6 months prior to the screening visit: stroke, transient ischemic attack (TIA), myocardial infarction, unstable angina, coronary revascularization, New York Heart Association (NYHA) class ≥ II cardiac insufficiency, severe unstable arrhythmia.
  • Hypertensive patients with poor blood pressure control (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg at the screening visit).
  • Patients with type 1 diabetes or type 2 diabetes with poor glycemic control (glycosylated hemoglobin > 8% at the screening visit).
  • Patients who have received treatment with 5-α reductase inhibitors (finasteride, dutasteride, enalidomide, epristeride, etc.) within 4 weeks before the first dose.
  • Has previously received goserelin.
  • Is receiving coumarin anticoagulants at the screening visit.
  • Has congenital long QT syndrome or QT/QTc interval prolongation (QTc ≥ 450 ms) at the screening visit; Or has received drugs that may prolong QT/QTc interval at the screening visit.
  • Known to be allergic to the active ingredients or any excipients of GnRH agonists or bicalutamide.
  • Patients who are seropositive for hepatitis B surface antigen (HBsAg), and must meet the following 2 conditions at the same time: 1. HBV DNA level: HBeAg-positive patients, HBV DNA ≥ 20,000 IU/ml [equivalent to 10^5 copies/mL]; HBeAg-negative patients, HBV DNA ≥ 2,000 IU/ml [equivalent to 10^4 copies/mL]; 2. ALT ≥ 2 x ULN); Patients who are seropositive for human immunodeficiency virus (HIV) antibody.
  • Alcoholics or drug abusers. Alcoholics are defined as drinking more than 14 units of alcohol per week within 3 months prior to the screening visit (1 unit = 350 mL beer, or 45 mL liquor, or 150 mL wine).
  • Has participated in any clinical trials of investigational drugs or medical devices, and discontinued within 1 month or 5 half-lives of the corresponding drug before the screening visit, whichever is longer.
  • Other conditions considered unsuitable for enrollment by the investigator (such as spinal cord compression due to prostate cancer metastatic lesions of pyramid, pulmonary interstitial disease or other serious diseases).

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: None (Open Label)

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: LY01005 3.6 mg
Intramuscular injections of LY01005 3.6 mg every 28 days for a maximum of 3 consecutive doses.
Drug: LY01005
LY01005 was administered as 3 intramuscular (IM) injections, 28 days apart. As concomitant medications, Casodex® (50 mg/day) was orally administered during the whole study period.
Other Names:
  • Goserelin Acetate Sustained-Release Microspheres for Injection
Active Comparator: ZOLADEX® 3.6 mg
Subcutaneous injections of ZOLADEX® 3.6 mg every 28 days for a maximum of 3 consecutive doses.
Drug: ZOLADEX® 3.6 mg
ZOLADEX® was administered as 3 Subcutaneous (SC) injections, 28 days apart. As concomitant medications, Casodex® (50 mg/day) was orally administered during the whole study period.
Other Names:
  • Goserelin Acetate Implant 3.6 mg

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
Time Frame
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Plasma concentration of goserelin over time.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Cmax.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Ctrough.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: AUC0-t.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: AUC0-∞.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Tmax.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: T1/2.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Vz/F.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Cl/F.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: MRT0-∞.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: accumulation of goserelin.
Time Frame: from baseline to Day 85
from baseline to Day 85

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
The percentage of subjects with serum testosterone ≤50 ng/dL (1.735 nmol/L) on Day 29 after the first dose.
Time Frame: Day 29 after the first dose
Day 29 after the first dose
The cumulative percentage of subjects with the maintenance of serum testosterone ≤50 ng/dL (1.735 nmol/L) from Day 29 to Day 85.
Time Frame: from Day 29 to Day 85
from Day 29 to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: AUEC of serum testosterone.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: Emax of serum testosterone.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: TEmax of serum testosterone.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: AUEC of serum LH.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: Emax of serum LH.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: TEmax of serum LH.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: AUEC of serum FSH.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: Emax of serum FSH.
Time Frame: from baseline to Day 85
from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: TEmax of serum FSH.
Time Frame: from baseline to Day 85
from baseline to Day 85
Significant Castration Rate.
Time Frame: from Day 29 to Day 85
The percentage of subjects with serum testosterone ≤20 ng/dL (0.7 nmol/L) on Day 29 after the first dose, and the cumulative percentage of subjects with the maintenance of serum testosterone ≤20 ng/dL (0.7 nmol/L) from Day 29 to Day 85.
from Day 29 to Day 85
The percentage of subjects with serum testosterone > 50 ng/dL on 1 hour, 4 hours, Day 3 and Day 7 after the second dose and the third dose.
Time Frame: 1 hour, 4 hours, Day 3 and Day 7 after the second dose and the third dose
1 hour, 4 hours, Day 3 and Day 7 after the second dose and the third dose
Percentage changes compared to baseline in serum FSH level after each administration.
Time Frame: Day 29, Day 57 and Day 85
Day 29, Day 57 and Day 85
Percentage changes compared to baseline in serum LH level after each administration.
Time Frame: Day 29, Day 57 and Day 85
Day 29, Day 57 and Day 85
Adverse events throughout the study.
Time Frame: up to Day 85
up to Day 85

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.
Luye Pharma Group Ltd.

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 (Actual)

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.
February 4, 2021

Primary Completion (Actual)

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.
September 15, 2021

Study Completion (Actual)

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 26, 2021

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).
November 3, 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.
November 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.
December 1, 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.
May 16, 2023

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.
May 15, 2023

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.
May 1, 2023

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.
  • LY01005/CT-CHN-104

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings