Benign prostatic hyperplasia (BPH) is a non malignant enlargement of the prostate due to cellular hyperplasia of both glandular and stromal elements. As the prostate increases in size it may exert pressure on the lumen of the prostatic urethra, resulting in a gradual obstruction to urine flow. MedDRA version: 8.1 Level: LLT Classification code 10004446
Conditions
Interventions
Product Name: Silodosin
Product Code: KMD 3213
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Silodosin
CAS Number: 160970-54-7
Sponsors
Recordati S.p.A
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Male subjects aged 50 years or older; 2. Presence at Visits 2 (start of placebo run-in) and 3 (baseline), of an IPSS-1 score of =13; 3. Presence of less than 25% decrease of the IPSS-1 score between Visit 2 (start of placebo run-in) and Visit 3 (baseline); 4. Presence at Visits 2 (start of placebo run-in) and 3 (baseline), of bladder outlet obstruction, as defined by a Qmax (peak urine flow rate) between 4 and 15 mL/sec, with a minimum voided volume of =125 mL; 5. Presence of a satisfactory compliance to study medication (80-120%) at Visit 3 (baseline); 6. Able to comply with protocol procedures; 7. Able to give written informed consent before beginning any investigational procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Post void bladder residual volume of greater than 250 mL determined by ultrasound (not evaluated at Visit 2); 2. Intravesical obstruction from any cause other than BPH including vesicle neck contracture, Mullerian duct cysts, urethral stricture, valves, sclerosis, or other urethral tumor; 3. Bladder calculi; 4. History of, or current, neurogenic bladder and other conditions that may affect bladder function including detrusor-sphincter dyssynergia, spinal cord injury, brain or spinal cord tumors, multiple sclerosis, diabetic neuropathies or dementia; 5. History of any type of procedure in the past that is considered intervention for BPH or bladder neck obstruction including prior TURP, bladder neck resection, thermotherapy, laser therapy, TUNA therapy, or any other minimally invasive surgical therapies specifically designed for relief of BPH; 6. An active urinary tract infection, or a history of recurrent urinary tract infections defined as greater than 3 per year in the past two years; 7. Current prostatitis or a diagnosis of chronic prostatitis, or at Visit 1, a history of prostatitis within the past 3 months or recurrent prostatitis more than 3 times in the last year; 8. History of urinary retention, from a cause other than BPH, within the past 3 months; 9. History of prior prostate cancer, or prostate cancer as suspected by TRUS, DRE or clinical acumen. Subjects with a PSA greater than 10.0 ng/ml will be excluded. Subjects with a PSA between 4.0 and 10.0 should have prostate cancer ruled out to the satisfaction of the clinical Investigator with appropriate documentation of the physician’s assessment; 10. History of prior invasive bladder cancer. Subjects with superficial bladder cancers that have not recurred in 5 years are eligible for protocol inclusion; 11. Prior radiation to the pelvis regardless of the reason or dosage of radiation; 12. Bladder catheterization or bladder or prostate instrumentation within the past 30 days; 13. History of, or current significant postural hypotension, and/or have experienced significant postural hypotension upon initiating therapy with an a-blocker. Significant postural hypotension is defined as any one of the following observations upon standing: a) systolic blood pressure (SBP) decrease >30 mmHg, b) diastolic blood pressure (DBP) decrease >20 mmHg, c) heart rate (HR) decrease >20 bpm, d) symptoms upon change of position such as lightheadedness, fainting, blurring or temporary loss of vision, profound weakness, or syncope; 14. Clinical significant cardiovascular and cerebrovascular disease in the last 6 months including: angina pectoris (with the exception of chronic stable angina occurring with strenuous, rapid or prolonged exertion), severe CHF (NYHA classes III-IV, see section 17.5.), acute myocardial infarction, poorly controlled hypertension (sustained SBP>160, DBP>95 mmHg), endocarditis, cardiac arrhythmias, prosthetic heart valves, cardiac devices, stroke, transient ischemic attacks; 15. Poorly controlled diabetes (HbA1c >8%); 16. Renal insufficiency (serum creatinine >2.0 mg/dL); 17. Liver insufficiency (any LFT >2xULN); 18. Hematuria which has not been appropriately evaluated to determine safe subject
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to test the hypothesis that the effectiveness of silodosin 8 mg given once daily for 12 weeks is superior to placebo and non-inferior to tamsulosin 0.4 mg given once daily for the relief of symptoms of BPH as measured by a baseline to endpoint change in the total score (questions 1 to 7) of the International Prostate Symptom Score-1 (IPSS-1). ; Secondary Objective: The secondary objectives are to compare the effectiveness and safety of silodosin to tamsulosin in a baseline to endpoint change in the following parameters: irritative symptoms subscore; obstructive symptoms subscore; QoL due to urinary symptoms (question 8 of IPSS-1); maximum urine flow (Qmax); percentage of treatment responders by IPSS-1 and by Qmax; and evaluation of adverse events, vital signs, ECGs, clinical laboratory tests and physical examinations. In a further step, as an optional extension to this protocol, the objective of the long-term open-label study period is to obtain long-term (6 and 12 months) safety data on silodosin 8 mg given as once daily treatment. Efficacy parameters will be also evaluated during long-term treatment. ; Primary end point(s): The International Prostate Symptom Score (IPSS-1) is a 8-item questionnaire designed to quantify the symptoms encountered most frequently with BPH and it has become the international standard. For questions 1-6, questions are graded on a 6-point scale with 0 = "not at all" and 5 = "almost always". For question 7, the descriptors are 0 = "none" to 5 = "5 or more times". The total score (questions 1 to 7) is a sum of each question's result. The primary efficacy parameter is based on this total score. The standard IPSS-1 (see Appendix 14.8 of the study protocol) will be assessed at visit 2 (entry criteria), visit 3 (entry criteria and baseline value) and at visit 6, 7 and 8. Validated local translations will be used in each country. | — |
Countries
Finland, Italy, Spain, United Kingdom
Outcome results
None listed