Symptomatic Study Investigating Degarelix in Patients Suffering From Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial was to see how well a new trial drug (degarelix) worked on lower urinary tract symptoms (also known as LUTS) in prostate cancer patients as compared to how a standard drug hormonal treatment worked on the same symptoms. The advancement/worsening of prostate cancer may be associated with LUTS and the symptoms may impact the ability to urinate normally and thereby the quality of life for these patients. Patients were randomly selected (like flipping a coin) to receive either degarelix or standard hormone therapy (combination of goserelin and bicalutamide) for a 3 month treatment period. During this period the relief of urinary symptoms was evaluated via a questionnaire filled in by patients and addressing the severity and frequency of their symptoms.

Official Title
-----------------
A Randomised, Parallel-arm, Open-label Trial Comparing Degarelix With Goserelin Plus Anti-androgen Flare Protection (Bicalutamide), in Terms of Reduction in International Prostate Symptom Score (IPSS), in Patients With Lower Urinary Tract Symptoms (LUTS) Secondary to Locally Advanced Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Degarelix
* Drug: Goserelin
* Drug: Bicalutamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has given written informed consent before any trial-related activity is performed Has a confirmed prostate cancer in which this type of treatment is needed. Exclusion Criteria: Previous treatment for prostate cancer Previous trans-urethral resection of the prostate Current use of 5-alpha reductase inhibitor or α-adrenoceptor antagonist. Patients in need of external beam radiotherapy to be started at the same time as hormone therapy Certain risk factors for abnormal heart rhythms/QT prolongation (corrected QT interval over 450 msec., Torsades de Pointes or use of certain medications with potential risk) History of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema. Hypersensitivity towards any component of the investigational product Other previous cancers within the last five years with the exception of prostate cancer and some types of skin cancer. Clinical disorders other than prostate cancer including but not limited to renal, haematological, gastrointestinal, endocrine, cardiac, neurological, psychiatric disease, alcohol or drug abuse or other conditionals as judged by the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 240 mg/80 mg<br>Degarelix 240 mg (40 mg/mL) + 80 mg (20 mg/mL) | Drug: Degarelix<br>* The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.<br>* Other names: FE200486;|
| Active Comparator: Goserelin (3.6 mg) + bicalutamide (50 mg)<br>Goserelin (3.6 mg) + bicalutamide (50 mg) | Drug: Goserelin<br>* Goserelin implants (3.6 mg) were inserted s.c. into the abdominal wall every 28 days. The second and third doses of goserelin were administered on Days 31 and 59, respectively.<br>* Other names: Zoladex;Drug: Bicalutamide<br>* On Day 0, three days before the first dose of goserelin on Day 3, patients began once-daily per-oral (p.o.) treatment with bicalutamide (50 mg) as anti-androgen flare protection; this treatment continued for 14 days after the first dose of goserelin.<br>* Other names: Casodex;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total International Prostate Symptom Score (IPSS) at Week 12 | The IPSS is a tool commonly used to assess the severity of lower urinary tract symptoms (LUTS), and to monitor the progress of the disease once treatment has been initiated. The participant completes a questionnaire containing 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5. The total score is then classified according to the following scale: 0 to 7 = mildly symptomatic; 8 to 19 = moderately symptomatic; and 20 to 35 = severely symptomatic. | After treatment of 12 weeks compared to Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total IPSS at Weeks 4 and 8 | The IPSS is a tool commonly used to assess the severity of lower urinary tract symptoms (LUTS), and to monitor the progress of the disease once treatment has been initiated. The participant completes a questionnaire containing 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5. The total score is then classified according to the following scale: 0 to 7 = mildly symptomatic; 8 to 19 = moderately symptomatic; and 20 to 35 = severely symptomatic. | After treatment of 4 and 8 weeks compared to Baseline | 
| Change From Baseline in Maximum Urine Flow (Qmax) at Each Visit | Uroflowmetry was used to quantify the maximum urine flow (Qmax; mL/sec) | After treatment of 4, 8 and 12 weeks compared to Baseline | 
| Change From Baseline in Residual Volume (Vresidual) at Each Visit | Uroflowmetry was used to quantify the residual volume (Vresidual; mL) | After treatment of 4, 8 and 12 weeks compared to Baseline | 
| Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 | TRUS is a method of measuring the size of the prostate. | After 12 weeks treatment compared to Baseline | 
| Number of Participants With Testosterone <=0.5 Nanograms/Milliliter at Each Visit |  | After treatment of 4, 8 and 12 weeks compared to Baseline | 
| Percentage Change From Baseline in Prostate-specific Antigen (PSA) Concentration at Each Visit |  | After treatment of 4, 8 and 12 weeks compared to Baseline | 
| Change From Baseline in Quality of Life (QoL) Related to Urinary Symptoms at Each Visit | The IPSS questionnaire included an additional single question to assess the participant's QoL in relation to his urinary symptoms. The question was: 'If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that?' The possible answers to this question ranged from 'delighted' (a score of '0') to 'terrible' (a score of '6'). The figures in the tables present the change (ie decrease) in IPSS QoL score, i.e. the bigger the decrease the better QoL. | After treatment of 4, 8 and 12 weeks compared to Baseline | 
| Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight | This outcome measure included incidence of markedly abnormal changes in blood pressure (systolic and diastolic), pulse, and body weight. The table presents the number of participants with normal baseline and at least one post-baseline markedly abnormal value. | Baseline to 12 weeks of treatment | 
| Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables | The figures present the number of participants who had abnormal (defined as above upper limit of normal range (ULN)) levels of safety laboratory variables. Only the laboratory variables that had at least on participant with one abnormal value are presented, many more variables were included in the trial. | Baseline to 12 weeks of treatment |