pharmacokinetics pharmacodynamics and safety of ly01022 in patients with prostate cancer compared with zoladex® 10.8mg

Conditions: Prostate Cancer

Summary: 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.


Eligibility criteria:
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).