Pharmacokinetics, pharmacodynamics and safety of a new Leuprolide acetate 22.5 mg depot formulation, when given as palliative treatment to prostate cancer patients

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-005964-24-GB
• Date of registration: 07/01/2007
• Prospective Registration: Yes
• Primary sponsor: Italfarmaco S.p.A.
• Public title: Pharmacokinetics, pharmacodynamics and safety of a new Leuprolide acetate 22.5 mg depot formulation, when given as palliative treatment to prostate cancer patients
• Scientific title: Pharmacokinetics, pharmacodynamics and safety of a new Leuprolide acetate 22.5 mg depot formulation, when given as palliative treatment to prostate cancer patients
• Date of first enrolment: 03/04/2007
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005964-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: Double blind: Parallel group: yes Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: administration route

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males >= 18 years of age, with histologically proven carcinoma of prostate, who might benefit from medical androgen deprivation therapy;
2. life expectancy of at least 1 year;
3. World Health Organization/Eastern Cooperative Oncology Group (WHO/ECOG) performance status of 0, 1, or 2;
4. adequate renal function at screening as defined by serum creatinine <= 1.5 times the upper limit of normal (ULN) for the clinical laboratory;
5. adequate and stable hepatic function as defined by bilirubin <= 1.5 times the ULN and transaminases (i.e. AST, ALT) <= 2.5 times the ULN for the clinical laboratory at screening;
6. ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study;
7. signed written informed consent prior to inclusion in the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Evidence of brain metastases, taking into account medical history, clinical observations and symptoms; evidence of spinal cord compression, taking into account medical history, clinical observations and symptoms; evidence of severe urinary tract obstruction with threatening urinary retention, taking into account medical history, clinical observations and symptoms; presence of any tumour in the immediate vicinity which could cause cord compression; severe pain from extensive osseous deposits, taking into account medical history, clinical observations and symptoms; testosterone levels less than 1.5 ng/mL at screening, locally determined at the laboratory of each clinical site; previous cancer systemic therapy such as chemotherapy, immunotherapy (e.g. antibody therapies, tumour-vaccines), biological response modifiers (e.g. cytokines) within 3 months of baseline; previous hormonal therapy for treatment of prostate cancer, such as LHRH analogues (no wash-out allowed); previous treatment with androgen receptor blockers, such as Casodex®, Fugerel®, Megace®, Androcur® (no wash-out allowed); previous orchiectomy, adrenalectomy or hypophysectomy; previous prostatic surgery within 2 weeks of baseline; previous local therapy to the primary tumour with a curative attempt other than surgery within 2 weeks of baseline; any investigational drug within 5 half-lives of its pharmacological action or 3 months, whichever is longer, before baseline; administration of 5-?-reductase inhibitors within 3 months before baseline; OTC or alternative medical therapies which have an estrogenic or anti-androgenic effect within the 3 months before baseline; haematological parameters outside 20% of the upper or lower limits of normal for the clinical laboratory at screening;
co-existent malignancy other than prostate cancer; uncontrolled congestive heart failure, myocardial infarction or a coronary vascular procedure or significant symptomatic cardiovascular disease(s) within 6 months before baseline; resting uncontrolled hypertension: (? 160/100 mmHg) or symptomatic hypotension within 3 months before baseline; venous thrombosis within 6 months of baseline;
uncontrolled diabetes (patients with uncontrolled diabetes need to compensate the metabolic disorder before treatment with LH-RH analogues); history of drug and/or alcohol abuse within 6 months of baseline; serious concomitant illness(es) or disease(s) that may interfere with, or put patients at additional risk for, their ability to receive the treatment outlined in the protocol; patients on anticoagulant therapy; blood donations/losses within 2 months of baseline, apart from previous prostatic surgery patients; known hypersensitivity to GnRH, GnRH agonist, including any LHRH analogues, or any excipients of the study formulation
history of the following prior to the study: immunization (within 4 weeks of baseline); flu shots (within 2 weeks of baseline); anaphylaxis; skin disease which would interfere with injection site evaluation; dermatographism will be documented at screening and followed up while on treatment



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Prostate cancer
MedDRA version: 8.1 Level: LLT Classification code 10007113 Term: Cancer of prostate

Intervention(s)

Product Name: Leuprolide acetate
Product Code: LF-LH
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: LEUPRORELIN ACETATE
CAS Number: 74381536
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 22.5-

Primary Outcome(s)

Primary end point(s): Part A:
- At least seven out of eight patients (i.e. 87.5%) achieving castrate levels of serum testosterone (< 0.5 ng/ml) on study day 28, and maintaining castrate levels of serum testosterone throughout the study up to study day 84 after single i.m. or s.c. injection of leuprolide acetate 22.5 mg.
- Leuprolide PK parameters after single i.m. or s.c. injection of leuprolide acetate 22.5 mg.

Part B:
- Number of patients achieving castrate levels of serum testosterone (< 0.5 ng/ml) on study day 28 and maintaining castrate levels of serum testosterone throughout the study up to day 84 following i.m. or s.c. administration of leuprolide acetate 22.5 mg.
- Leuprolide PK parameters after single i.m. or s.c. injection of leuprolide acetate 22.5 mg.

Main Objective: Part A: preliminary investigation of the safety, pharmacodynamics and pharmacokinetics of a new leuprolide acetate depot 3-month formulation after i.m. or s.c. administration to patients with prostate cancer.

Part B: investigation of the safety, pharmacodynamics and pharmacokinetics of a new leuprolide 3-month formulation in patients with prostate cancer after administration of a single dose of 22.5 mg leuprolide acetate by i.m. or s.c. injection (according to the results of study part A, see § 3.2).

Secondary Objective: -Main testosterone PD parameters (see § 9.2.1).
-Serum FSH / LH concentrations, PSA concentrations.
-WHO/ECOG performance status (scores) (see Appendix B), bone pain, urinary pain/urinary symptoms.

Secondary ID(s)

CRO-06-78 / DSC/06/LEU15/01