E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007113 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy of the study treatment in reducing plasma testosterone below castration levels |
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E.2.2 | Secondary objectives of the trial |
Determination of serum LH, FSH and PSA concentrations; World Health Organization/Eastern Cooperative or Group (WHO/ECOG) performance status, bone pain, urinary symptoms and urinary pain after administration.
Evaluation of the safety of the new formulation based on: adverse events, local tolerability, vital signs, ECGs and clinical laboratory parameters.
Determination of plasma leuprolide levels (only 12 subjects - PK group) |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Males at least 18 years of age or above, with histologically proven carcinoma of prostate, who might benefit from medical androgen deprivation therapy; life expectancy of at least 1 year; World Health Organization/Eastern Cooperative or Group (WHO/ECOG) performance status of 0, 1, or 2; adequate renal function at screening as defined by serum creatinine less than or equal to 1.6 times the ULN (upper limit of normal) for the clinical laboratory; adequate and stable hepatic function as defined by bilirubin less than or equal to 1.5 times the ULN and transaminases (i.e. SGOT, SGPT) less than or equal to 2.5 times the ULN for the clinical laboratory at screening; 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; signed written informed consent prior to inclusion in the study. |
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E.4 | Principal exclusion criteria |
Evidence of brain metastases, spinal cord compression, evidence of severe urinary tract obstruction with threatening urinary retention and excruciating, severe pain from extensive osseous deposits in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms; testosterone levels < 1.5 ng/mL at screening; previous cancer systemic therapy such as chemotherapy, immunotherapy (e.g. antibody therapies, tumor-vaccines), biological response modifiers (e.g. cytokines) within 3 months of baseline; previous hormonal therapy for treatment of prostate cancer, such as LHRH analogues (e.g. Lupron®, Zoladex®); previous treatment with AR-receptor blockers, such as Casodex®, Fugerel®, Megace®, Androcur®; previous orchiectomy, adrenalectomy or hypophysectomy; previous prostatic surgery (e.g. radical prostatectomy, TUR-P) within 2 weeks of baseline; previous local therapy to the primary tumor with a curative attempt other than surgery (external beam radiotherapy, brachytherapy, thermotherapy, cryotherapy) within 2 weeks of baseline; any investigational drug within 5 half-lives of its physiological action or 3 months, whichever is longer, of baseline; administration of 5-a-reductase inhibitors (Proscar®, Avodart®, Propecia®) within 3 months of baseline; OTC or alternative medical therapies which have an estrogenic or anti-androgenic effect within the 3 months of baseline; hematological parameters (RBC, total and differential WBC count, platelet count, hemoglobin, hematocrit) outside 20% of the upper or lower limits of normal (ULN, LLN) for the clinical laboratory at screening; co-existent malignancy; uncontrolled congestive heart failure, myocardial infarction or a coronary vascular procedure or significant symptomatic cardiovascular disease(s) within 6 months of baseline; resting uncontrolled hypertension or symptomatic hypotension within 3 months of baseline; venous thrombosis within 6 months of baseline; insulin-dependent diabetes mellitus; history of drug and/or alcohol abuse within 6 months of baseline; serious concomitant illness(es) or disease(s); patients receiving anticoagulants who have prothrombin and partial thromboplastin times outside of the normal range for the laboratory assays. Patients who are on anticoagulation or antiplatelet medications (e.g. dipyridamole, ticlopidine, warfarin derivatives) who are not receiving a stable dose for 3 months before baseline. Patients who are receiving warfarin-derivative anticoagulants who do not have an International Normalized Ratio (INR) in the therapeutic range for the clinical indication for which the anticoagulant has been prescribed; blood donations/losses within 2 months of baseline, apart from previous prostatic surgery patients (please note that these patients should not be included in the PK group); known hypersensitivity to GnRH, GnRH agonist, including any LHRH analogues, or any excipients of the study formulation; history of 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine:
1. The proportion of patients achieving castration levels of plasma testosterone (defined as <0.5 ng/mL) 4 weeks after the 1st administration; 2. The proportion of patients maintaining castration levels of plasma testosterone from week 4 to study end; 3. The proportion of patients showing acute rises in plasma testosterone levels upon repeated dosing (the so-called “acute-on-chronic” phenomenon).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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the last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |