• Change from baseline in Prostate Specific antigen (PSA) levels. [ Time Frame: At each treatment visit ] [ Designated as safety issue: No ]
• Mean testosterone concentration [ Time Frame: Measured at each treatment visit ] [ Designated as safety issue: No ]
• "Acute-on-chronic" changes in testosterone and Luteinizing Hormone (LH) levels [ Time Frame: From just prior to the second (Week 24) injection through the visit 14 days post-second injection ] [ Designated as safety issue: No ]

• Change from baseline in PSA levels [ Time Frame: At each treatment visit ] [ Designated as safety issue: No ]
• Mean testosterone concentration [ Time Frame: Measured at each treatment visit ] [ Designated as safety issue: No ]
• "Acute-on-chronic" changes in testosterone and LH levels [ Time Frame: From just prior to the second (Week 24) injection through the visit 14 days post-second injection ] [ Designated as safety issue: No ]

The purpose of this study is to access the efficacy and safety of two new formulations of leuprolide acetate 45 mg 6-month depot formulations in treating patients with prostate cancer.

Subjects will receive a total of two intramuscular injections, administered 24 weeks apart.

Approximately 300 male subjects will be enrolled. The first 150 enrolled will receive Formulation A for both injections and the next 150 will receive Formulation B for both injections.

This study will be conducted by approximately 60-80 investigative sites. Patients will participate in the trial for approximately 14 months.

This trial includes a Screening Period (up to 4 weeks), 12-month Treatment Period (two 6 month treatment cycles), and a Follow-Up Period (30 days). This trial will include a total of 20 visits (Screening Visit, 18 Treatment Period Visits, and a Post-Treatment Follow-Up Visit).

• Drug: Leuprolide acetate formulation A
• Drug: Leuprolide acetate formulation B

• Experimental: Leuprolide acetate Formulation A
• Experimental: Leuprolide acetate Formulation B

Inclusion Criteria:

• Voluntarily sign an IRB-approved informed consent form and any required privacy statement/authorization form.
• Pre-trial serum testosterone level >150 ng/dL.

• Histologically-confirmed prostatic adenocarcinoma in Jewett Clinical Stage A2, B, C or D and TNM* classification cT1b-4, N: any, M: any.

  *Tumor/Nodes/Metastases

• Subjects with a rising PSA following radical prostatectomy defined as an increase of 0.2 ng/dL from the previous test on two consecutive testings or rising PSA following prostate irradiation using Phoenix Definition of a rise of greater than or equal to 2.0 ng/dL above the nadir.
• Prostate cancer and general clinical status is sufficient to warrant at least 48 weeks of continuous androgen deprivation treatment, without concomitant antiandrogen treatment.
• Eastern Cooperative Oncology Group (ECOG) Performance status grades 0,1,or 2 at the time of pre-trial screening.
• Life expectancy of at least 18 months.
• Subjects with serum creatinine ≤1.9 mg/dL, bilirubin ≤2.0 mg/dL (unless Gilbert's syndrome with normal AST, ALT); AST and ALT ≤2.5 times the ULN.

Exclusion Criteria:

• Requires additional treatment including radical prostatectomy, radiotherapy or cryotherapy of local disease
• Historical, clinical, or radiographic evidence of central nervous system metastases, including spinal cord metastasis.
• Clinical evidence of urinary tract obstruction.
• History of bilateral orchiectomy, adrenalectomy, or hypophysectomy.
• History of clinical hypogonadism.
• Current malignancy or history of malignancy except for prostate cancer or basal or squamous cell carcinoma of the skin.
• Clinical or laboratory evidence of any severe underlying disease state (excluding prostate cancer) that would place subjects in additional jeopardy by participating in this trial.
• Hypersensitivity to leuprolide, polylactic acid, or any excipient of the drug.
• Incomplete recovery from the effects of any major surgery.
• History of receiving of the following prostate cancer therapies within 8 weeks prior to the Screening Visit: chemotherapy, immunotherapy, antiandrogen, radiation therapy, cryotherapy, strontium, or biological response modifiers.
• History of prostatic surgery within 4 weeks prior to the Screening Visit.
• Received hormonal therapy, including GnRH analogs (less than or equal to 6 month depot administration), estrogen, Megace and phytotherapy, within 32 weeks prior to the Screening Visit and during the trial.
• Alternative medical therapies which have an estrogenic, androgenic, or antiandrogenic effect (including phyto-estrogens and phyto-androgens) within 12 weeks prior to the Screening Visit and during the trial.
• Requires the chronic use of systemic corticosteroids and anticonvulsants that may affect bone loss such as carbamazepine, phenobarbital, phenytoin, valproic acid or primidone.
• May require antiandrogen, immuno-, or surgical therapy for prostate cancer during the trial.
• History of alcoholism or consumes >14 alcoholic beverages per week or illicit drug abuse within 12 months prior to screening.
• Received therapy with a GnRH analog 1 year implant within 60 weeks prior to the Screening Visit.
• Received therapy with finasteride or ketoconazole within 1 week prior to the Screening Visit; dutasteride within 25 weeks prior to the Screening Visit.