E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Benign Prostata Hypertropia (BPH) who fulfil the following criteria: a prostate volume of more than 30 mL, maximal uroflow of 12 mL/s or less; International Prostate Symptom Score (IPSS) of 13 or more, a serum prostate specific antigen (PSA) value below 10 ng/mL and no evidence of prostate cancer will be included in the study |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004447 |
E.1.2 | Term | Benign prostatic hypertrophy |
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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 explore the pharmakokinetic/pharmacodynamic relationships at different doses of degarelix in benign prostatic hyperplasia (BPH) patients and to select doses and dosing regime for Phase II efficacy trials. |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety of different doses of degarelix.
To explore possible pharmacodynamic effects of degarelix 64 mg (40 mg/mL) on the secretion of androgens from the adrenal glands.
To explore the long term efficacy at different doses of degarelix in BPH patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A signed written informed consent before any study related activity is performed. 2. Man, 45 to 75 years of age. 3. Clinical diagnose of BPH with a prostate volume more than 30 mL, a maximal uroflow of 12 mL/sec or less and an IPSS of 13 or more at screening. See Section 7.1.4 for a description of the assessments. 4. A PSA value less than 10 ng/mL and no clinical evidence of adenocarcinoma of the prostate at screening. If a biopsy of the prostate is performed, a period of 6 weeks should be allowed after the biopsy before the patient is enrolled into the study. 5. Has a baseline testosterone level above 3 ng/mL at screening. 6. A Body Mass Index (BMI) between 18 kg/m2 and 32 kg/m2 and a body weight between 50 kg and 120 kg. 7. Has negative serology for Human Immunodeficiency Virus (HIV) 1, HIV 2, hepatitis B surface antigen, and hepatitis C virus antibody.
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E.4 | Principal exclusion criteria |
1. Previous surgery of the prostate. 2. Previous treatment with GnRH agonists or GnRH antagonists. 3. Treatment with 5-alpha reductase inhibitors, e.g., finasteride (Prosca®)or dutasteride (Avodart®) within the past 12 months before the study. 4. Treatment with alpha-adrenergic antagonists, e.g., terazosin, doxazosin, tamsulosin, alfuzosin (see Appendix 4) within 2 weeks prior to Screening part II (or Part I, if IPSS is performed at Screening part I). 5. A clinically significant neurological, gastrointestinal, renal, hepatic cardiovascular, psychological, pulmonary, metabolic, endocrine, haematological, dermatological or infectious disorder or any other condition including excessive alcohol or drug abuse, which may interfere with trial participation or which may affect the conclusion of the study as judged by the investigator. 6. Diagnosed cancer within the last 10 years except for adequately managed basal cell carcinoma and squamous cell carcinoma of the skin. 7. Present or a history of severe allergy or anaphylactic reactions. 8. A history of hypersensitivity to or is hypersensitive to any component of the investigational medicinal product. 9. A significant acute illness within two weeks prior to screening. 10. Any clinically significant laboratory abnormalities, which in the judgement of the investigator would interfere with the patient’s participation in this study or evaluation of the study results. Liver transaminases must be within normal limits. 11. Treatment with any drug modifying the testosterone level (see Appendix 3) or function within 12 weeks before Screening visit part II (or Part I, if IPSS is performed at Screening part I). 12. Donation of more than 700 mL blood within the last 10 months before the start of study. 13. Has a mental incapacity or language barriers precluding adequate understanding, co-operation, and compliance. 14. Is considered by the Investigator unsuitable to participate in the study for any other reason. 15. Has received an investigational medicinal product within the last one month for single dose studies (otherwise three months) before entering the study or longer if judged by the investigator to possibly influence the outcome of the current study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacodynamics:
Testosterone concentration-time profiles Area of testosterone below the baseline, minimal value of testosterone at baseline (Cnadir) and time of Cnadir (tnadir), Area of testosterone when testosterone concentration is below 0.5 ng/mL, Time with testosterone concentrations below 0.5 ng/mL, Proportion of patients at or below a testosterone level of 0.5 ng/mL at each time point, Time for return to baseline. Proportion of patients with baseline testosterone levels at each time point. Other pharmacodynamic endpoints: Serum concentration values at each time point of DHT, LH, free testosterone and PSA Maximal change from baseline in serum concentration values of DHEA, DHEAS and androstendione Serum concentration values at each time point of DHEA, DHEAS and androstendione Endpoints relating to efficacy: Peak urinary flow, post-void residual volume (PVR), and prostate volume compared to baseline. Patient reported outcomes: IPSS score, IPSS global quality of life (QoL) and International Index of Erectile Function (IIEF) domain scores compared to baseline.
Pharmacokinetics:
AUC, AUCt, % Extrap AUC, Cmax, tmax, CL/F, Vz/F, λz and t½ of degarelix determined by non-compartmental analysis.
Safety:
Number and type of adverse events, vital signs, 12-lead electrocardiogram (ECG), clinical chemistry, haematology, urinalysis, and physical examination
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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 | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Different degarelix dosages and regimens |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |