A Trial of Degarelix in Men With Lower Urinary Tract Symptoms (LUTS) Associated With Benign Prostatic Hyperplasia (BPH)

Study Overview
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Brief Summary
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A dose-finding, multi-centre, double-blind, randomised, parallel, placebo-controlled trial to investigate efficacy and safety of degarelix in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH)

Official Title
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A Dose-Finding, Multi-Centre, Double-Blind, Randomised, Parallel, Placebo-Controlled Trial to Investigate Efficacy and Safety of Degarelix in Men With Lower Urinary Tract Symptoms (LUTS) Associated With Benign Prostatic Hyperplasia (BPH)

Conditions
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Lower Urinary Tract Symptoms (LUTS)

Intervention / Treatment
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* Drug: Placebo
* Drug: Degarelix 10 mg
* Drug: Degarelix 20 mg
* Drug: Degarelix 30 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent obtained before any trial-related activity is performed Men, aged 50 or older Clinical signs and symptoms of BPH for ≥6 months Moderate to severe LUTS at screening, as defined by International Prostate Symptom Score (IPSS) ≥13 An IPSS QoL score of ≥3 at screening Prostate specific antigen (PSA) at screening ≤10 ng/mL (responsibility of the Investigator to rule out prostate cancer when PSA is >4 ng/mL, except in the USA where patients with a PSA >4 and ≤10 ng/mL should undergo a prostatic biopsy or have a negative prostatic biopsy within 12 months prior to participation in the trial) Maximum urinary flow (Qmax) ranging between 5 to 15 mL/second with a minimum voided volume >125 mL at screening Exclusion Criteria: Post void residual volume (PVR) >250 mL Stone in the bladder or urethra causing symptoms Acute or chronic prostatitis Interstitial cystitis / painful bladder syndrome Acute or recurrent urinary tract infections History of acute urinary retention (AUR) Lower urinary tract instrumentation (including prostate biopsy) within 30 days of dosing at Visit 2 Clinical evidence of any of the following urinary tract conditions: Mullerian duct cysts Atonic, decompensated, or hypocontractile bladder Detrusor-sphincter dyssynergia (contraction of the detrusor without sphincter relaxation) History of any of the following pelvic conditions: Pelvic surgery or any other pelvic procedure, including radical prostatectomy, pelvic surgery for removal of malignancy, or open lower colonic or rectal surgery Pelvic radiotherapy Any prior surgical procedure of the urinary tract, including minimally invasive LUTS/BPH therapies Lower tract malignancy or trauma Clinically significant microscopic haematuria at screening History of significant renal insufficiency, defined as receiving renal dialysis or having an estimated creatinine clearance <30 mL/minute at screening Systolic blood pressure >180 or <90 mmHg or diastolic blood pressure >110 or <50 mmHg at screening or malignant hypertension Any causes other than BPH, which may affect evaluation of symptoms of urine flow (e.g. neurogenic bladder, bladder neck contracture, urethral stricture, and bladder malignancy) as judged by the Investigator Use of any prohibited therapies Elevated liver function tests at screening: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) >2 times the upper limit of normal Total bilirubin >1.5 times the upper limit of normal QTc interval on the screening ECG >450 ms, or a family history of long QT syndrome Any clinically significant disorder (other than BPH) including, but not limited to, renal, haematological, gastrointestinal, endocrine, cardiac, neurological, or psychiatric disease, or any other condition, which may affect the patient's health or the outcome of the trial as judged by the Investigator Diagnosed cancer within the last 5 years except for adequately managed basal cell carcinoma and squamous cell carcinoma of the skin History of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema Mental incapacity or language barrier precluding adequate understanding or co-operation History or current evidence of drug, alcohol, or substance abuse within 6 months prior to screening Hypersensitivity towards any component of the investigational medicinal product (IMP) Previous participation in any degarelix trial

Ages Eligible for Study
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Minimum Age: 50 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Mannitol 50 mg/mL solution<br>|
| Experimental: Degarelix 10 mg<br> | Drug: Degarelix 10 mg<br>* 10 mg degarelix, 40 mg/mL solution<br>* Other names: Firmagon;|
| Experimental: Degarelix 20 mg<br> | Drug: Degarelix 20 mg<br>* 20 mg degarelix, 40 mg/mL solution<br>* Other names: Firmagon;|
| Experimental: Degarelix 30 mg<br> | Drug: Degarelix 30 mg<br>* 30 mg degarelix, 40 mg/mL solution<br>* Other names: Firmagon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in International Prostate Symptom Score (IPSS) | This outcome measure was used to assess the dose-response of the 3 degarelix dose groups in terms of severity of lower urinary tract symptoms (LUTS) and progress of the disease process, versus the placebo group. One treatment month equals 28 days. The IPSS questionnaire is a tool commonly used to assess the severity of LUTS, and to monitor the progress of the symptoms during treatment. It contains 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5 (i.e. minimum total score is 0 and the maximum score is 35), where 0 corresponds to a response of not at all for the first six symptoms and none for nocturia, and 5 corresponds to a response of almost always for the first six symptoms and 5 times or more for nocturia. The IPSS also includes a question to evaluate a patient's quality of life in relation to his urinary symptoms, which is not included in the total IPSS score. | From Baseline to Month 3 after Dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in IPSS | This secondary outcome measure was used to assess the maintained dose-response of the 3 degarelix dose groups in terms of severity of LUTS and progress of the disease process, versus the placebo group. | From Baseline to Month 4, Month 5 and Month 6 after Dosing | 
| Odds Ratio (as Compared to Placebo) of Treatment Response in IPSS | A 3-point reduction in IPSS score compared to baseline is defined as a clinically meaningful treatment response. Percentage of participants who met criteria for a clinically meaningful treatment response and odds ratios of treatment responses between each degarelix dose group and the placebo group are presented. | At Month 3, Month 4, Month 5 and Month 6 after Dosing | 
| Mean Percentage Change in Total Prostate Volume (TPV) | TPV was measured directly by standardised trans-rectal ultrasound (TRUS). | From Baseline to Month 3 and Month 6 after Dosing | 
| Mean Change in Maximum Urinary Flow (Qmax) | Urinary flow rate (mL/second) was measured using uroflowmetry performed according to the recommendation from the International Continence Society (ICS). | From Baseline to Month 3 and Month 6 after Dosing |