A MULTI-CENTER, RANDOMIZED, PARALLEL GROUP, DOUBLE-BLIND, PLACEBO CONTROLLED PROOF OF CONCEPT AND DOSE RANGING STUDY WITH AN ACTIVE CONTROL TO ASSESS THE EFFICACY AND SAFETY/TOLERABILITY OF UK-369,003 IMMEDIATE RELEASE (IR) AND MODIFIED RELEASE (MR) IN THE TREATMENT OF MEN WITH LOWER URINARY TRACT SYMPTOMS (LUTS) WITH AND WITHOUT ERECTILE DYSFUNCTION (ED)

Conditions: ower urinary tract symptoms (LUTS) in men with and without erectile dysfunction (ED).
MedDRA version: 8.1Level: LLTClassification code 10046566Term: Urinary tract disorder

Registration Number: EUCTR2006-004378-28-LV

Lead Sponsor: Pfizer Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 414

Inclusion Criteria

1. Male subjects aged 40 years and above, with documented LUTS with an International Prostate Symptom Score (IPSS) =13 at both visit 1 (screening) and visit 3 (baseline).
2. Clinical diagnosis of BPH.
3. Qmax 5 to 15ml/sec with a voided volume of =150ml at visit 1 (screening).
4. Stable sexual partner for the duration of the trial.
5. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspectsof the trial.
6. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests and other trial 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

1. History, evidence or suspicion of prostate cancer (includes total Prostate Specific Antigen (PSA) value > 10 ng/ml unless prostate cancer previously excluded by biopsy) at visit 1 (screening) or during the course of the trial.
2. Post-void residual urine volume >200ml based on bladder ultrasound at visit 1
(screening).
3. Documented urinary tract infection (UTI) at visit 1 (screening) or visit 3 (baseline);
subjects with a positive (1+ or greater) leukocyte or nitrite result in urine dipstick test will be excluded unless UTI can be ruled out via urine culture.
4. Greater than 1+ of hematuria on dipstick test at visit 1 (screening), unless fully
investigated prior to randomization at visit 3 (baseline) to rule out significant urological disease.
5. History of relevant urological surgery or procedures that may contribute to LUTS
6. Chronic persistent local lower urinary tract pathology
7. Known primary neurological conditions such as multiple sclerosis, Parkinson’s disease, or other neurological diseases known to affect bladder function.
8. History of catheterization for outflow obstruction in the previous 12 months prior to visit 1 (screening) or visit 3 (baseline).
9. Subjects receiving or who are likely to receive any of the following medications or
treatments during the trial period.
a. a-blockers, muscarinic receptor antagonists, PDE5 inhibitors, and agents known to
affect vesico-urethral function or erectile function
b. 5-a-RIs such as dutasteride and finasteride
c. Diuretics, beta-blockers or other anti-hypertensive agents
d. Nitrates or nitric oxide donors in any form on either regular or intermittent basis
e. Potent CYP3A4 inhibitors. Topical agents are permitted.
f. Warfarin.
10. Significant allergy to or known hypersensitivity or intolerance to a-blockers or PDE5 inhibitors.
11. Increased susceptibility to vasodilators including those subjects with left ventricular outflow obstruction (e.g., hypertrophic obstructive cardiomyopathy).
12. Poorly controlled type I or type II diabetes mellitus as defined by HbA1C >7% at visit 1 (screening).
13. Loss of vision in one eye due to non-arteritic ischemic optic neuropathy (NAION)
regardless of whether or not this event was temporarily associated with the use of a PDE5 inhibitor.
14. Hereditary degenerative retinal disorders (e.g. retinitis pigmentosa).
15. History of recurrent syncope or evidence of low blood pressure (BP) (<90mmHg systolic or <40mmHg diastolic) or evidence of symptomatic postural hypotension. This includes relevant postural symptoms associated with fall in systolic BP of > 20 mmHg or diastolic BP > 10 mmHg on standing at visit 1(screening) or visit 3 (baseline).
16. Any relevant clinically significant abnormalities on visit 1 (screening) physical
examination or laboratory tests including subjects with moderate liver function tests
abnormalities (see Appendix 8) and renal function abnormalities (serum creatinine =2.5 mg/dl or =220 µmol/l).
17. Family history of prolonged QT syndrome or who themselves have a QTc of >450 msec at visit 1 (screening) as measured by a 12-lead supine ECG.
18. Risk of priapism e.g. sickle cell disease, multiple myeloma and myeloproliferative
disorders (e.g. myeloid leukemia, polycythemia, thrombocythemia).
19. Subjects currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the trial, or to comply with the requirements of the protocol, including: dermatologic disease,