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

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

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.

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).