Leuprolide Acetate 3.75 mg Depot Injection for Patients With Advanced Prostate Cancer

Inclusion criteria

• Male subjects aged above 18 years.
• Histologically or cytologically confirmed adenocarcinoma of the prostate at stage T1b-4, Nany, Many in subjects, who would benefit from a GnRH agonist.
• Baseline Testosterone of >1.50 ng/mL or >150 ng/dL.
• For subjects with radical prostatectomy, an increase of 0.2 ng/mL or 20 ng/dL in PSA from previous test on two consecutive tests. For subjects with prostate irradiation a rise of greater than or equal to 2.0 ng/mL or 200 ng/dL PSA above the nadir.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Appendix 2).
• Life expectancy of at least 6 months from screening.
• Adequate organ and immune system function
• Willing to participate and sign the informed consent as per regulatory requirements.

Exclusion criteria

• Evidence of brain metastases.
• Evidence of spinal cord compression.
• Evidence of urinary tract obstruction, where a flare in disease could put subject at significant risk in the opinion of the Investigator.
• Received prostate cancer therapies like immunotherapy (antibody therapies, tumor vaccines), external radiotherapy, brachytherapy, chemotherapy or biological response modifiers (e.g. cytokines) within two months of enrollment.
• Undergone any prostate surgery (e.g. transurethral resection of the prostate (TURP), radical prostatectomy) within two weeks of enrollment.
• Under the effects of any other hormonal therapy, including anti-androgens for treatment of prostate cancer within three months of baseline.
• Received leuprolide (leuprorelin) previously.
• Had an orchiectomy, adrenalectomy or hypophysectomy.
• Had used any investigational drug, biologic, or device within five half-lives of its physiological action or three months, whichever is longer, before enrollment.
• Anticipated to need concomitant hormonal, anti-androgen, radiotherapy, chemotherapy, immunotherapy or surgical therapy for prostate cancer throughout the duration of the study.
• Used over-the-counter (OTC) or alternative medical therapies which has an estrogenic or anti-androgenic effect (e.g., Glycyrrhiza, Dehydroepiandrosterone (DHEA), PC-SPES, saw palmetto) within three months prior to enrollment.
• Used finasteride, dutasteride, estrogens, megestrol acetate, anti-androgens (Bicalutamide, Flutamide, or Cyproterone), and ketoconazole within three months prior to baseline.
• Co-existent malignancy or a history of malignancy, with the exception of basal and/or squamous cell carcinomas of the skin.
• Uncontrolled congestive heart failure within six months before baseline.
• Experienced a myocardial infarction or a coronary vascular procedure (e.g. balloon angioplasty, coronary artery bypass graft surgery) within six months before baseline.
• Significant symptomatic cardiovascular disease within six months of baseline.
• Experienced venous thrombosis within six months of baseline.
• Uncontrolled hypertension (≥160/100 mmHg) or symptomatic hypotension within three months before baseline.
• Insulin-dependent diabetes mellitus (Type I diabetes mellitus).
• History of drug abuse within six months of baseline.
• Serious intercurrent illnesses or diseases (e.g. hematological, renal, hepatic, respiratory, endocrine, psychiatric) that might interfere with the treatment outlined in the protocol.
• Receiving anticoagulants or antiplatelet medications and not receiving a stable dose for three months before baseline. Receiving warfarin-derivative anticoagulants with International normalized ratio (INR) outside therapeutic range for the clinical indication for which the anticoagulant has been prescribed.
• Known hypersensitivity to GnRH, GnRH agonists or any excipients of Leuprolide (leuprorelin).
• Positive test for HIV, HCV, HbsAg at Screening.
• History of:

• Immunization within four weeks of baseline
• Flu shots within two weeks of baseline
• Donation or receipt of blood or blood products within two months of baseline
• Anaphylaxis
• Skin disease which would interfere with injection site evaluation
• Dermatographism (Physical urticaria).