Explorative Study of Degarelix for Treatment of Benign Prostatic Hyperplasia.

Study Overview
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Brief Summary
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This exploratory study will be conducted open label in a single investigational clinical unit. Altogether 52 patients with benign prostate hyperplasia (BPH) will be randomly assigned to receive 4 different treatments with degarelix.

Detailed Description
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The present study aims at exploring the potential of the currently available formulation of degarelix to treat BPH with only a short transient lowering of the serum testosterone concentration to or below the castration level defined as 0.5 ng/mL. Two doses and two dosing regimens (32 and 64 mg administered either as a single administration or as two administrations separated by 14 days) will be evaluated for 42 days.

Official Title
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A Single-centre, Open-label, Randomised Explorative Pharmacokinetic/Pharmacodynamic Study of the Gonadotropin-releasing Hormone Receptor Antagonist Degarelix (FE 200486) in Patients With Benign Prostatic Hyperplasia.

Conditions
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BPH

Intervention / Treatment
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* Drug: Degarelix
* Drug: Degarelix
* Drug: Degarelix
* Drug: Degarelix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each patient must comply with all of the following inclusion criteria to be allowed to be randomised into the study: Man, 55 to 75 years of age. Clinical diagnose of BPH with a prostate volume more than 30 mL, a maximal uroflow of 12 mL/sec or less and an international prostate sympton score (IPSS) of 13 or more at screening. A prostate specific antigen (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. Has a baseline testosterone level above 3 ng/mL at screening. Exclusion Criteria: Any patient meeting one or more of the following exclusion criteria will not be included into the study: Previous surgery of the prostate. Previous treatment with GnRH agonists or GnRH antagonists. Treatment with 5-alpha reductase inhibitors, e.g., finasteride (Prosca®)or dutasteride (Avodart®) within the past 12 months before the study. Treatment with alpha-adrenergic antagonists, e.g., terazosin, doxazosin, tamsulosin, alfuzosin within 2 weeks prior to Screening part II (or Part I, if IPSS is performed at Screening part I). Treatment with any drug modifying the testosterone level or function within 12 weeks before Screening visit part II (or Part I, if IPSS is performed at Screening part I).

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Degarelix 16+16 mg<br> | Drug: Degarelix<br>* Two doses of 16 mg each administered as two administrations (separated by 14 days) will be evaluated for 42 days.<br>|
| Experimental: Degarelix 32 mg<br> | Drug: Degarelix<br>* One dose of 32 mg administered as a single administration will be evaluated for 42 days.<br>|
| Experimental: Degarelix 32+32 mg<br> | Drug: Degarelix<br>* Two doses of 32 mg each administered as two administrations (separated by 14 days) will be evaluated for 42 days.<br>|
| Experimental: Degarelix 64 mg<br> | Drug: Degarelix<br>* One dose of 64 mg administered as a single administration will be evaluated for 42 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Testosterone Area Below Baseline Interval | The area of the testosterone concentration (ng/mL) vs. time (days) curve that is below the baseline interval concentration( i.e. 0.75 x baseline concentration) | 0-42 Days | 
| Time of Testosterone Concentration Below Baseline Interval | The time from when the testosterone concentration falls below the baseline interval limit (i.e. 0.75 x baseline concentration) until it returns above this limit | Day 0-42 | 
| Minimal Value of Testosterone (Cnadir) | The lowest concentration of testosterone measured within the time frame | Day 0-42 | 
| Time of Minimal Value of Testosterone (Tnadir) | The time point when the lowest testosterone concentration was measured | Day 0-42 | 
| Duration of Testosterone Concentration Below 0.5 ng/mL | The time from when the testosterone concentration falls below 0.5 ng/mL until it returns above that level | Day 0-42 | 
| Number of Subjects With Testosterone Concentration ≤0.5 ng/mL |  | Day 0-42 | 
| Number of Subjects With Testosterone Concentration at or Above the Baseline Interval Concentration | The baseline interval concentration is 0.75 x baseline concentration | Day 0-42 | 
| Prostate Specific Antigen (PSA) Concentration |  | Day 0-42 | 
| Prostate Volume | The prostatic volume was measured by transrectal ultrasound. The prostatic gland was sonicated from two directions perpendicular to one another resulting in three cursor positions set by the urologist, and the volume automatically calculated. | Day 0-42 | 
| Maximal Urinary Flow | Urinary flow was determined by flowmetry using a device that fulfils the International Continence Society standards for maximum urinary flow. | Day 0-42 | 
| Post-void Residual Urine Volume | The post-void residual urine volume in the bladder was evaluated by transabdominal ultrasound. The urine bladder was sonicated from two directions perpendicular to one another, and the volume calculated automatically. | Day 0-42 | 
| International Prostate Specific Symptom (IPSS) Score | The IPSS is a patient-administered questionnaire containing seven items to evaluate symptoms of urinary obstruction (incomplete emptying, frequency, hesitancy, urgency, weak stream, straining, nocturia) over the preceding week. Each urinary symptom question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The total score can therefore range from 0 to 35 (0-7: mildly symptomatic; 8-19: moderately symptomatic; 20-35: severely symptomatic). | Day 0-42 | 
| IPSS Global Quality of Life | Patients were asked about how they would feel if they were to spend the rest of their lives with their prostate symptoms just as they are now. The answers choices range from delighted to terrible or 0 to 6. | Day 0-42 | 
| Interntional Iindes of Erectile Function (IIEF) Score: Overall Satisfaction | The IIEF contains 15 items in 5 domains: Erectile Function (6 items), Orgasmic Function (2 items), Sexual Desire (2 items), Intercourse Satisfaction (3 items), and Overall Satisfaction (2 items). Item are scored on a scale from 'No sexual activity' to 'Almost always to always'. For the Erectile Function domain, a score of 1-10 indicates severe erectile dysfunction and 26-30 no dysfunction, the minimum score being 1 and the maximum 30. For all other domains, a higher score indicates less dysfunction. The IIEF does not yield a total score. | Day 0-42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters of Degarelix: AUCt | Area under the time-concentration curve (AUCt) was calculated by non-compartmental methods based on data up to Day 42 | 0-42 Days | 
| Pharmacokinetic Parameters of Degarelix: Cmax | Cmax was determined for concentration measurements up to Day 42 | Day 0-42 | 
| Pharmacokinetic Parameters of Degarelix: Tmax | The time for maximal concentration (tmax) was determined for data up to Day 42 | Day 0-42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Benign Prostate Hyperplasia, BPH, PK/PD, GnRH antagonist