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

An Open-Labeled, Singled-Arm Study of the Safety, Efficacy, and Pharmacokinetic Behavior of Leuprolide Mesylate for Injectable Suspension (LMIS 50 mg) in Subjects With Advanced Prostate Carcinoma

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.

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: Leuprolide Mesylate

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.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Universitätsklinik für Urologie und Andrologie, Landeskrankenhaus Salzburg (University hospital for Urology and Andrology)
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4020
      • AKH Linz GmbH, Department of Urology
• Czechia
  • Hradec Králové, Czechia, 500 05
    • University Hospital Hradec Kralove
  • Olomouc, Czechia, 779 00
    • University Hospital Olomouc
  • Praha 4 - Krč
    • Praha, Praha 4 - Krč, Czechia, 140 59
      • Thomayerova nemocnice Urologické oddělení
• Germany
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
      • Universitätsklinikum RWTH Aachen, Klinik für Urologie
• Lithuania
  • Kaunas, Lithuania, 50009
    • PI Hospital of Lithuanian University of Health Sciences, Kauno Klinikos
  • Klaipėda, Lithuania, 92288
    • PI Klaipėda University Hospital
  • Vilnius, Lithuania, 08661
    • PI Vilnius University Hospital, Santariškių Klinikos
• Poland
  • Gdańsk, Poland, 80-402
    • Uniwersyteckie Centrum Kliniczne, Klinika Urologii
  • Warzawa, Poland, 02-507
    • Centralny Szpital Kliniczny MSW w Warszawie, Klinika Urologii i Urologii Onkologicznej
  • Warzawa, Poland, 02-781
    • Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Układu Moczowego
  • Łódź, Poland, 90-265
    • "DERMED" Centrum Medyczne Sp. z o.o.
• Slovakia
  • Prešov, Slovakia
    • UROCENTRUM MILAB, s.r.o.
  • Žilina, Slovakia, 012 07
    • Fakultná nemocnica s poliklinikou Žilina Urológia
• Taiwan
  • Taoyuan City, Taiwan, 333
    • Chang Gung Memorial Hospital, LinKou (CGMH-LK)
  • Pingtung
    • Kaohsiung City, Pingtung, Taiwan, 813
      • Kaohsiung Veteran General Hospital (VGHKS)
  • Taichung
    • Taichung City, Taichung, Taiwan, 404
      • China Medical University Hospital (CMUH)
    • Taichung City, Taichung, Taiwan, 407
      • Taichung Veteran General Hospital (VGHTC)
  • Tainan
    • Tainan City, Tainan, Taiwan, 704
      • National Cheng Kung University Hospital (NCKUH)
  • Taipei
    • Taipei City, Taipei, Taiwan, 100
      • National Taiwan University Hospital (NTUH)
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Urology Centers Of Alabama
  • California
    • Laguna Hills, California, United States, 92653
      • Alliance Research Centers
    • San Diego, California, United States, 92123
      • Genesis Research, LLC
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute - Meridian
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • AdvanceMed Research
  • North Carolina
    • Concord, North Carolina, United States, 28025
      • Carolina Clinical Trials, LLC
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Washington
    • Burien, Washington, United States, 98166
      • Seattle Urology Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Leuprolide Mesylate 50mg; All subjects will be males with advanced prostate carcinoma. They will be 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 will be followed until day 336.	Drug: Leuprolide Mesylate; Subcutaneous injection of 50mg Leuprolide Mesylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	baseline to 28 days, 28 days to 336 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	Safety analysis was based on the safety information from the laboratory evaluations, AEs, and SAEs.	336 days

Collaborators and Investigators

• Sponsor: Foresee Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ACTUAL): August 30, 2016
• Study Completion (ACTUAL): January 5, 2017

Study Registration Dates

• First Submitted: September 1, 2014
• First Submitted That Met QC Criteria: September 4, 2014
• First Posted (ESTIMATE): September 9, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 5, 2019
• Last Update Submitted That Met QC Criteria: February 20, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Prostate Neoplasm Cancer Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Carcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: FP01C-13-001; 2013-001790-25 (EUDRACT_NUMBER)