Safety, Efficacy, and Pharmacokinetic Behavior of Leuprolide Mesylate (LMIS 25 mg) in Subjects With Prostate Cancer

An Open-Label, Single-Arm Study of The Efficacy, Safety, and Pharmacokinetic Behavior of Leuprolide Mesylate Injectable Suspension (LMIS 25 mg) in Subjects With Prostate Cancer

The study will evaluate if Leuprolide Mesylate is safe and effective in the treatment of subjects with prostate cancer, when administered as two injections twelve weeks apart.

This is a multi-national, multi-center, open-label, single-arm study. All subjects will be males with prostate cancer judged to be candidates for medical androgen ablation therapy and all will receive two injections of LMIS 25 mg twelve-week 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 opinion
   • Serum glucose within acceptable range according to investigator's opinion
   • HgbA1c within acceptable range according to investigator's opinion
   • 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:

1. 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.
2. Receipt of any vaccination (including influenza) within 4 weeks of screening visit
3. History of blood donation within 2 months of screening visit
4. History of anaphylaxis to any LH-RH analogues
5. Receipt of any LHRH suppressive therapy within 6 months of screening visit
6. Major surgery, including any prostatic surgery, within 4 weeks of screening visit
7. History and concomitant clinical and radiographic evidence of central nervous system/spinal cord metastases and subjects at risk for spinal cord compression
8. Clinical evidence of active urinary tract obstruction and subjects at risk for urinary obstruction
9. History of bilateral orchiectomy, adrenalectomy, or hypophysectomy
10. History or presence of hypogonadism, or receipt of exogenous testosterone supplementation within 6 months of Baseline
11. Clinically significant abnormal ECG and/or history of clinically significant cardiovascular disease as judged by the investigator
12. History of drug and/or alcohol abuse within 6 months of Baseline
13. Contraindication to leuprolide or an LHRH agonist as indicated on package labeling
14. Use of 5-alpha reductase inhibitor within the last 6 months of screening visit
15. History or presence of insulin-dependent diabetes mellitus (Type I). Presence of well controlled diabetes mellitus Type II will be allowed if only oral hypoglycemic are required. Prostate cancer subjects with poor controlled diabetes mellitus with Hb1Ac > 9.5% or urine glycosuria > 1.0 g/dL should be excluded.
16. Use of systemic corticosteroids at a dose >10 mg/d or anti-androgens
17. Use of any investigational agent within 4 weeks of screening visit
18. Use of any over-the-counter (OTC) medication within 4 weeks of screening visit except for those listed in the permitted Concomitant Treatment section.
19. 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