Prostate Carcinoma MedDRA version: 20.0 Level: LLT Classification code 10036921 Term: Prostate carcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Leuprolide Mesylate injectable suspension 25mg
Product Code: LMIS 25 mg
Pharmaceutical Form: Suspension for injection in pre-filled syringe
INN or Proposed INN: Leuprolide Mesylate
Curre
Sponsors
Foresee Pharmaceuticals Co., Ltd.
Eligibility
Sex/Gender
Male
Inclusion criteria
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 o Absolute neutrophil count = 1,500 cells/µL o Platelets = 100,000 cells/µL o Hemoglobin = 10 gm/dL o Total bilirubin = 1.5 × upper limit of normal (ULN) o AST (SGOT) = 2.5 × ULN o ALT (SGPT) = 2.5 × ULN o Serum creatinine = 1.5 mg/dL o Lipid profile within acceptable range according to investigator’s opinion o Serum glucose within acceptable range according to investigator’s opinion o HbA1c = 9.5% o Clinical chemistries (K, Na, Mg, Ca and P) within acceptable range according to Investigator’s opinion o Normal urinalysis results within: • RBCs = 3 RBCs/hpf • WBCs = 5 WBCs/hpf • Nitrate: negative • Glucose: =65 years) yes F.1.3.1 Number of subjects for this age range 123
Exclusion criteria
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) Patients who were previously enrolled in the LMIS 50 mg study (7) Major surgery, including any prostatic surgery, within 4 weeks of screening visit (8) History and concomitant clinical and radiographic evidence of central nervous system/spinal cord metastases and subjects at risk for spinal cord compression (9) Clinical evidence of active urinary tract obstruction and subjects at risk for urinary obstruction (10) History of bilateral orchiectomy, adrenalectomy, or hypophysectomy (11) History or presence of hypogonadism; or receipt of exogenous testosterone supplementation within 6 months of screening visit (12) Clinically significant abnormal ECG and/or history of clinically significant cardiovascular disease as judged by the investigator (13) History of drug and/or alcohol abuse within 6 months of screening visit (14) Contraindication to leuprolide or an LHRH agonist as indicated on package labeling (15) Use of 5-alpha reductase inhibitor within the last 6 months of screening visit (16) 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. (17) Use of systemic corticosteroids at a dose > 10 mg/d or anti-androgens (18) Use of any investigational agent within 4 weeks of screening visit (19) Use of any over-the-counter (OTC) medication within 4 weeks of screening visit except for those listed in the permitted Concomitant Treatment section (20) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: LMIS 25 mg is the mesylate salt of leuprolide and has the same biological activity profile as leuprolide acetate salt. It is a luteinizing hormone-releasing hormone (LH-RH) agonist acting as a potent inhibitor of gonadotropin secretion when given in therapeutic doses, and lowers testosterone levels to castrate levels. Leuprolide is the standard of care for palliative treatment of prostate cancer. This study is designed to evaluate the safety, efficacy, and pharmacokinetic (PK) profile of LMIS 25 mg when given as two separate subcutaneous injections administered 12 weeks apart in subjects with prostate cancer. 1. Primary objective: To assess the efficacy and safety of LMIS 25 mg for up to 24 weeks following 2 subcutaneous doses given 12 weeks apart in subjects with prostate cancer. ;Secondary Objective: To establish a PK profile of serum leuprolide for LMIS 25 mg in a subset of subjects with prostate cancer. ;Primary end point(s): To determine the percentage of subjects with a serum testosterone concentration suppressed to castrate levels (= 50 ng/dL) on Day 28 ± 1 day (week 4) following administration of LMIS 25 mg, and the proportion of subjects with serum testosterone suppression (= 50 ng/dL) maintained from Day 28 ± 1 day (week 4) through Day 168 ± 5 days (week 24). ;Timepoint(s) of evaluation of this end point: 1. Safety and tolerability Endpoints: Visits 1-23 2. Efficacy evaluation: Visits 1-23 3. Evaluation of pharmacokinetics: Visits 2-23 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. The proportion of subjects exhibiting post-suppression excursions of serum testosterone: Visits 2-23 2. Effect of LMIS 25 mg on serum PSA levels: Visits 2-23 3. Effect of LMIS 25 mg on serum LH levels: Visits 2-23;Secondary end point(s): 2.1 Efficacy: • The mean acute-on-chronic (surge) changes in testosterone and LH levels from just prior to the second injection through 14 days after the second injection of LMIS 25 mg (Day 98, week 14) • Effect of LMIS 25 mg on serum LH levels • Effect of LMIS 25 mg on serum prostate-specific antigen (PSA) levels • The percentage of subject with PSA relapse defined as after achieving the serum PSA level = 4 ng/mL post LMIS 25 mg injection but with an increase in serum PSA of >50% PSA nadir by Day 168± 5 days (week 24) • The percentage of subject achieving normal serum PSA level (<4 ng/dL) on Day 168 ± 5 days (week 24) • The percentage of subjects with enhanced serum testosterone concentration suppression to = 20 ng/dL on Day 28 ± 1 day (week4) and on Day 168 ± 5 days (week 24). 2.2 Safety: • Adverse event (AE)/ serious adverse event (SAE) reporting • Assessment of injection site reaction • Change in bone pain measurement (by Visual Analogue Scale [VAS] scale) • Change in urinary signs and symptoms and total scores assessed by the International Prostate Symptom Score (I-PSS) sheet • Change in vital signs (BP, HR, RR, weight) • Change in physical examinations with clinical significance compared to baseline by principal investigator’s judgment • Change in lab data, including liver function (AST, ALT, ALP), renal function (BUN, SCr), complete blood count with platelets, clinical chemistries (K, Na, Mg, Ca and P), urinalysis, serum glucose, lipid profile (LDL, HDL, triglycerides) and HbA1c level • Clinically significant changes in 12-lead resting electrocardiogram (ECG) per the investigator’s judgment. 2.3 Pharmacokinetic: • The serum pharmacokinetic profile of leuprolide for up to 26 | — |
Countries
Czech Republic, Korea, Republic of, Lithuania, Slovakia, United States
Contacts
Public ContactClinical Trials Information
Clinical Accelerator Ltd.
Outcome results
None listed