Leuprolide Acetate 3.75 mg Depot to Treat Prostate Cancer

Inclusion Criteria:

• Males >/= 18 years of age, with histologically proven carcinoma of the prostate, who might benefit from medical androgen deprivation therapy
• Life expectancy of at least 1 year
• World Health Organization/Eastern Cooperative Oncology Group (WHO/ECOG) performance status of 0, 1, or 2
• Adequate renal function at screening as defined by serum creatinine </= 1.6 times the ULN (upper limit of normal) for the clinical laboratory
• Adequate and stable hepatic function as defined by bilirubin </= 1.5 times the ULN and transaminases (i.e. SGOT, SGPT) </= 2.5 times the ULN for the clinical laboratory at screening
• Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study
• Signed written informed consent prior to inclusion in the study

Exclusion Criteria:

• Evidence of brain metastases, in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms
• Evidence of spinal cord compression, in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms
• Evidence of severe urinary tract obstruction with threatening urinary retention, in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms
• Excruciating, severe pain from extensive osseous deposits, in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms
• Testosterone levels < 1.5 ng/mL at screening, locally determined at the laboratory of each clinical site
• Previous cancer systemic therapy such as chemotherapy, immunotherapy (e.g. antibody therapies, tumor-vaccines), biological response modifiers (e.g. cytokines) within 3 months of baseline
• Previous hormonal therapy for treatment of prostate cancer, such as luteinising hormone-releasing hormone (LHRH) analogues (e.g. Lupron®, Zoladex®, etc.) [no wash-out allowed]
• Previous treatment with androgen receptor (AR) blockers, such as Casodex®, Fugerel®, Megace®, Androcur® (no wash-out allowed)
• Previous orchiectomy, adrenalectomy or hypophysectomy
• Previous prostatic surgery (e.g. radical prostatectomy, transurethral resection of the prostate [TUR-P]) within 2 weeks of baseline
• Previous local therapy to the primary tumor with a curative attempt other than surgery (external beam radiotherapy, brachytherapy, thermotherapy, cryotherapy) within 2 weeks of baseline
• Any investigational drug within 5 half-lives of its physiological action or 3 months (whichever is longer) before baseline
• Administration of 5-alpha-reductase inhibitors (Proscar®, Avodart®, Propecia®) within 3 months before baseline
• Over-the-counter (OTC) or alternative medical therapies which have an estrogenic or anti-androgenic effect (i.e., PC-SPES, saw palmetto, Glycyrrhiza®, Urinozinc®, dehydroepiandrosterone [DHEA]) within the 3 months before baseline
• Hematological parameters (RBC, total and differential WBC count, platelet count, hemoglobin, hematocrit) outside 20% of the upper or lower limits of normal (ULN, LLN) for the clinical laboratory at screening
• Co-existent malignancy, according to the Investigator's opinion
• Uncontrolled congestive heart failure, myocardial infarction or a coronary vascular procedure (e.g. balloon angioplasty, coronary artery bypass graft) or significant symptomatic cardiovascular disease(s) within 6 months before baseline; resting uncontrolled hypertension: (>/= 160/100 mmHg) or symptomatic hypotension within 3 months before baseline
• Venous thrombosis within 6 months of baseline
• Insulin-dependent diabetes mellitus
• History of drug and/or alcohol abuse within 6 months of baseline
• Serious concomitant illness(es) or disease(s) [e.g., hematological, renal, hepatic, respiratory, endocrine, psychiatric] that may interfere with, or put patients at additional risk for, their ability to receive the treatment outlined in the protocol
• Patients receiving anticoagulants who have prothrombin and partial thromboplastin times outside of the normal range for the laboratory assays; patients who are on anticoagulation or antiplatelet medications (e.g. dipyridamole, ticlopidine, warfarin derivatives) who are not receiving a stable dose for 3 months before baseline; patients who are receiving warfarin-derivative anticoagulants who do not have an International Normalized Ratio (INR) in the therapeutic range for the clinical indication for which the anticoagulant has been prescribed.
• Blood donations/losses within 2 months of baseline, apart from previous prostatic surgery patients (see earlier exclusion [9]; please note that these patients should not be included in the pharmacokinetic [PK] group)
• Known hypersensitivity to GnRH, GnRH agonist, including any LHRH analogues, or any excipients of the study formulation

• History of the following prior to the study:

  • immunization (within 4 weeks of baseline);
  • flu shots (within 2 weeks of baseline);
  • anaphylaxis;
  • skin disease which would interfere with injection site evaluation;
  • dermatographism will be documented at screening and followed up while on treatment.