Pharmacokinetics Pharmacodynamics and Safety of LY01022 in Patients With Prostate Cancer Compared With Zoladex® 10.8mg

Study Overview
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Brief Summary
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This is a randomized, open-label, Parallel, active-controlled phase I study. A total of 20-24 patients with locally advanced or metastatic prostate cancer will be randomized in a 1:1 ratio to receive a single injection of LY01022 10.8mg or Zoladex® 10.8mg. Blood samples will be collected to evaluate PK and PD profiles, and safety evaluation will be conducted as required in the protocol.

Official Title
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A Randomized, Open-label, Parallel, Active-controlled Phase 1 Study to Compare Pharmacokinetics Pharmacodynamics and Safety of Goserelin Acetate Sustained-Release Microspheres for Injection (LY01022) With Zoladex® 10.8mg Following Single Administration in Patients With Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Goserelin Acetate Sustained-Release Microspheres for Injection
* Drug: Zoladex 10.8 MG Drug Implant


Participation Criteria
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Eligibility Criteria
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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 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 ≤ 3×ULN (or ≤ 5.0×ULN for patients with liver metastases). 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 6 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. Patients who are receiving coumarin anticoagulants at the screening visit. Have 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 HIV antibody or HCV 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). Have participated in any clinical trials of investigational drugs or medical devices, and discontinued within 1 month before the screening visit. 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY01022<br> | Drug: Goserelin Acetate Sustained-Release Microspheres for Injection<br>* 10.8mg, Single dose, subcutaneously（SC）<br>* Other names: LY01022;|
| Active Comparator: Zoladex®<br> | Drug: Zoladex 10.8 MG Drug Implant<br>* 10.8mg, Single dose, subcutaneously（SC）<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma goserelin concentration after administration of LY01022 or Zoladex® |  | from baseline to Day 99 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum testosterone concentration after administration of LY01022 or Zoladex® |  | from baseline to Day 99 | 
| Changes in serum luteinizing hormone (LH) concentration after administration of LY01022 or Zoladex® |  | from baseline to Day 99 | 
| Changes in serum follicle stimulating hormone (FSH) concentration after administration of LY01022 or Zoladex® |  | from baseline to Day 99 | 
| Adverse events throughout the study |  | from baseline to Day 99 |