Safety, Efficacy, and Pharmacokinetic Behavior of Leuprolide Mesylate in Subjects With Advanced Prostate Carcinoma

This is a multi-center, open-label, single-arm study conducted in 2 parts. Part I was
established to provide a vanguard of the first 30 subjects who will have more frequent
monitoring of their safety. If safety is established, the remainder of the subjects will be
entered into the clinical study (i.e., Part II). All subjects will be males with advanced
prostate carcinoma judged to be candidates for medical androgen ablation therapy, and all
will receive two injections of LMIS 50 mg six-month apart in an unblinded fashion.

Inclusion Criteria:

1. Males aged ≥ 18 years old

2. Males with histologically confirmed carcinoma of the prostate

3. Subjects who are judged by the attending physician and/or Principal Investigator to be
a candidate for androgen ablation therapy

4. Baseline morning serum testosterone level > 150 ng/dL performed at Screening Visit

5. Eastern Cooperative Oncology Group (ECOG) Performance score ≤ 2

6. Life expectancy of at least 18 months

7. Laboratory values

- Absolute neutrophil count ≥ 1,500 cells/µL

- Platelets ≥ 100,000 cells/µL

- Hemoglobin ≥ 10 gm/dL

- Total bilirubin ≤ 1.5 × upper limit of normal (ULN)

- AST (SGOT) ≤ 2.5 × ULN

- ALT (SGPT) ≤ 2.5 × ULN

- Serum creatinine ≤ 1.5 mg/dL

- Lipid profile within acceptable range according to investigator's judgment

- HgbA1c within acceptable range according to investigator's judgment

- Clinical chemistries (K, Na, Mg, Ca and P) within acceptable range according to
investigator's judgment

- Serum glucose within acceptable range according to investigator's judgement

- Urinalysis within normal range according to the investigator's judgment

8. Agree to use male contraceptive methods during study trial

9. Based on the Investigator's judgment, the ability to understand the nature of the
study and any hazards of participation, and to communicate satisfactorily with the
Investigator and to participate in, and to comply with, the requirements of the entire
protocol

10. All aspects of the protocol explained and written informed consent obtained

Exclusion Criteria:

- Receipt of chemotherapy, immunotherapy, cryotherapy, radiotherapy, or anti- androgen
therapy concomitantly, or within 8 weeks prior to Screening Visit, for treatment of
carcinoma of the prostate. Radiation for pain control will be allowed during the
study.

- Receipt of any vaccination (including influenza) within 4 weeks of Baseline

- History of blood donation within 2 months of Baseline

- History of anaphylaxis to any LH-RH analogues

- Receipt of any LHRH suppressive therapy within 6 months of Baseline

- Major surgery, including any prostatic surgery, within 4 weeks of Baseline

- History and concomitant clinical and radiographic evidence of central nervous
system/spinal cord metastases. Subjects at risk for spinal cord compression will be
excluded.

- Clinical evidence of active urinary tract obstruction and subjects at risk for urinary
obstruction

- History of bilateral orchiectomy, adrenalectomy, or hypophysectomy

- History or presence of hypogonadism, or receipt of exogenous testosterone
supplementation within 6 months of Baseline

- Clinically significant abnormal ECG and/or history of clinically significant
cardiovascular disease as judged by the investigator

- History of drug and/or alcohol abuse within 6 months of Baseline

- Contraindication to leuprolide or an LHRH agonist as indicated on package labeling

- Use of 5-alpha reductase inhibitor within the last 6 months of Baseline

- History or presence of insulin-dependent diabetes mellitus (Type I). Presence of well
controlled diabetes mellitus Type II will be allowed

- Use of systemic corticosteroids at a dose >10 mg/d or anti-androgens

- Use of any investigational agent within 4 weeks of Baseline

- Use of any over-the-counter (OTC) medication within 4 weeks of Baseline except for
those listed in the permitted Concomitant Treatment section.

- Uncontrolled intercurrent illness that would jeopardize the subject's safety,
interfere with the objectives of the protocol, or limit the subject's compliance with
study requirements, as determined by the Investigator in consultation with the Sponsor