Prostatic Neoplasms
Conditions
Keywords
Prostate Neoplasm Cancer Carcinoma
Brief summary
The study will evaluate if Leuprolide Mesylate is safe and effective in the treatment of subjects with advanced prostate carcinoma, when administered as two injections six months apart.
Detailed description
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.
Interventions
Subcutaneous injection of 50mg Leuprolide Mesylate
Sponsors
Foresee Pharmaceuticals Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Leuprolide Mesylate (LMIS 50mg) | baseline to 28 days, 28 days to 336 days | The percentage of subjects with a serum testosterone concentration suppressed to castrate levels (≤ 50 ng/dL) following the first injection of LMIS 50 mg from Day 28 through Day 336 (remaining duration of the study). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | 336 days | Safety analysis was based on the safety information from the laboratory evaluations, AEs, and SAEs. |
Countries
Austria, Czechia, Germany, Lithuania, Poland, Slovakia, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Leuprolide Mesylate 50mg All subjects were males with advanced prostate carcinoma. They were injected twice with a depot formulation containing 50 mg of Leuprolide Mesylate. The first dose on day 0 the second dose on day 168 (six months apart). Subjects were followed until day 336.
Leuprolide Mesylate: Subcutaneous injection of 50mg Leuprolide Mesylate | 137 |
| Total | 137 |
Baseline characteristics
| Characteristic | Leuprolide Mesylate 50mg |
|---|---|
| Age, Continuous | 71.1 years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 73 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 123 Participants |
| Region of Enrollment Austria | 1 Participants |
| Region of Enrollment Czechia | 17 Participants |
| Region of Enrollment Germany | 1 Participants |
| Region of Enrollment Lithuania | 29 Participants |
| Region of Enrollment Poland | 5 Participants |
| Region of Enrollment Slovakia | 18 Participants |
| Region of Enrollment Taiwan | 2 Participants |
| Region of Enrollment United States | 64 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 137 |
| other Total, other adverse events | 114 / 137 |
| serious Total, serious adverse events | 20 / 137 |
Outcome results
Primary
Efficacy of Leuprolide Mesylate (LMIS 50mg)
The percentage of subjects with a serum testosterone concentration suppressed to castrate levels (≤ 50 ng/dL) following the first injection of LMIS 50 mg from Day 28 through Day 336 (remaining duration of the study).
Time frame: baseline to 28 days, 28 days to 336 days
Population: ITT
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Leuprolide Mesylate 50mg | Efficacy of Leuprolide Mesylate (LMIS 50mg) | 97.0 percentage of participants |
Secondary
Number of Participants With Adverse Events (AEs)
Safety analysis was based on the safety information from the laboratory evaluations, AEs, and SAEs.
Time frame: 336 days
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Leuprolide Mesylate 50mg | Number of Participants With Adverse Events (AEs) | TEAE | 114 Participants |
| Leuprolide Mesylate 50mg | Number of Participants With Adverse Events (AEs) | Drug-related AEs | 85 Participants |
| Leuprolide Mesylate 50mg | Number of Participants With Adverse Events (AEs) | SAE | 20 Participants |