E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced, recurrent, or metastatic carcinoma of the prostate indicated for endocrine therapy |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007462 |
E.1.2 | Term | Carcinoma prostate |
E.1.2 | System Organ Class | 100000004864 |
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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 demonstrate that Acino Goserelin 3.6 mg implant is effective in achieving and maintaining castration levels of testosterone. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males between 18 and 89 years of age at the start and for the duration of the study 2. Diagnosis of locally advanced, recurrent, or metastatic carcinoma of the prostate indicated for endocrine therapy 3. Testosterone values of >1.5 ng/mL at Screening (Visit 1) 4. Life expectancy of at least 6 months 5. Written informed consent
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E.4 | Principal exclusion criteria |
1. Hypersensitivity to Zoladex or to other gonadotropin releasing hormone (GnRH) analogs 2. Previous androgen deprivation therapy, treatment with GnRH analogs, treatment with antiandrogens or androgen receptor blockers is not allowed within 3 months before baseline, except treatment with non-steroidal antiandrogens as described in the protocol. 3. Concomitant treatment with any GnRH analogs. Patients who previously underwent an intermittent treatment scheme may be included if no more than 2 treatment cycles were received. A treatment cycle is defined as the continuous and repeated administration of a GnRH analog (according to the prescribing information) until a discontinuation of treatment based on the patient’s physical and / or disease status as judged by the investigator. The re-initiation of a subsequent GnRH analog administration (based on medical judgement) after the treatment discontinuation is defined as the start of a new treatment cycle. 4. Considered for curative therapy i.e. radical prostatectomy or radiotherapy within 2 months from inclusion 5. Cancer diagnosis within the last 5 years except prostate cancer, low grade bladder cancer, and surgically removed basocellular or squamous cell carcinoma of the skin 6. Uncontrolled cardiac disease, including myocardial infarction within 12 months before screening, congestive heart failure (CHF) New York Heart Association (NYHA) functional classification of ≥3, unstable angina, abnormal blood pressure, severe cardiac arrhythmias, electrolyte abnormalities, congenital long QT syndrome, or cerebrovascular disease including stroke within 3 years of screening. 7. History of abnormal blood pressure, unless adequately controlled with conventional treatment. Normal blood pressure is defined as BP <=140/90 mm Hg and >=90/60 mm Hg for those below 80 years of age, or <=150/90 mm Hg and >=90/60 mm Hg for those above 80 years of age. NOTE: In case patients present with abnormal BP readings at Visit 1 then they may get treated for hypertension by a doctor, and return for the Visit 2 assessments. If their BP values are found acceptable at Visit 2, they can still be included in the study. 8. Concomitant medication of class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medications as well as bupropion, moxifloxacin, and SSRIs. 9. Uncontrolled diabetes mellitus, or HbA1c>9%, at the time of screening or diabetic complications (retinopathy, neuropathy, nephropathy, PAD) within the past year. 10. Medical history or concurrent condition of psychiatric disorders, such as psychotic disorders and depression. 11. Medical history of seizures, convulsions, epilepsy, central nervous system anomalies, tumors, or anticonvulsive treatment. 12. Medical history or current condition osteoporosis. 13. Condition of ureteric obstruction or spinal cord compression. 14. Previous orchiectomy, adrenalectomy, or hypophysectomy 15. Medical history of any clinically significant neurological, gastrointestinal, renal, hepatic, respiratory, endocrine, hematological, dermatological or infectious disorder or other condition including alcohol or drug abuse, which may interfere with study participation or which may affect the conclusion of the study as judged by the investigator (using the ECOG [Eastern Cooperative Oncology Group] performance scale; patients who have an ECOG performance status of ≥3 will be excluded). 16. Mental incapacity or language barriers precluding adequate understanding or co-operation or willingness to follow study procedures 17. Previous participation in this study 18. Known allergy against one of the ingredients in the test or reference preparation 19. Having used any investigational medication or medical device in the 12 weeks prior to Screening or scheduled to use another investigational medication or medical device during the study 20. Participation in another clinical study within 30 days before screening 21. Absence of effective contraception (i.e. use of condoms or sexual abstinence) 22. Employee at the investigational site, relative or spouse of the investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
Testosterone response rate defined as testosterone values sustained below castration level (0.5 ng/mL) i.e. all testosterone values at and after Day 28 until Day 56 must be < 0.5 ng/mL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At and after Day 28 until Day 56 (Days 28, 31, 35, 42, 49 and 56) |
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E.5.2 | Secondary end point(s) |
Efficacy: E1 - Percentage of patients who have reached castration level of testosterone (<0.5 ng/mL) at the last visit (Day 56) E2 - Time course of testosterone levels on Days 28, 31, 35, 42, 49, 56 E3 - Time after first implantation until castration level of testosterone is achieved E4 - Rate of patients with testosterone values sustained below 0.2 ng/mL at and after Day 28 until Day 56 E5 - Results of clinical examination of the prostate E6 - Prostate-specific antigen (PSA) level
Pharmacokinetics and luteinizing hormone/folligcle stimulating hormone (LH/FSH): P1 - Plasma levels of goserelin, luteinizing hormone/follicle stimulating hormone (LH/FSH) between Day 0 (first implantation) and Day 56 (last visit)
Safety and tolerability: S1 - Adverse events S2 - Electrocardiogram (ECG) at the day of implantation, prior to implantation, and at study end S3 - Safety laboratory (including glucose and HbA1c) S4 - Vital signs, and body weight S5 - Local Tolerability
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy: E1 - Day 56 E2 - Days 28, 31, 35, 42, 49, 56 E3 - Day at which castration level of testosterone is achieved E4 - At and after Day 28 until Day 56 (Days 28, 31, 35, 42, 49 and 56) E5 - Day 56 E6 - Days 28, 31, 35, 42, 49, 56
Pharmacokinetics and luteinizing hormone/follicle stimulating hormone (LH/FSH): P1 - Days 1, 2, 4, 7, 14, 21, 28, 31, 35, 42, 49, 56
Safety and tolerability: S1 - Informed consent until all follow-ups have been concluded after the end of the study S2 - Day 56 S3 - Safety laboratory: Days 14, 28, 56; Glucose: Days 1, 2, 4, 7, 14, 21, 28, 31, 35, 42, 49, 56; HbA1c: Day 56 S4 - Vital signs: Days 1, 2, 4, 7, 14, 21, 28, 31, 35, 42, 49, 56; body weight: Day 28, Day 56 S5 - Days 1, 7, 28, 35, 56 |
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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 | Yes |
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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |