Lower urinary tract symptoms (LUTS) in men with and without erectile dysfunction (ED). MedDRA version: 8.1 Level: LLT Classification code 10046566 Term: Urinary tract disorder
Conditions
Interventions
Product Name: UK-369,003-Besylate
Product Code: UK-369,003-26
Pharmaceutical Form: Modified-release tablet
CAS Number: 334827-98-4
Current Sponsor code: UK-369,003-26
Other descriptive name: UK-369,00
Sponsors
Pfizer Ltd
Eligibility
Sex/Gender
Male
Inclusion criteria
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
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) ( 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,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: ;Primary end point(s): The primary endpoint used to assess efficacy is the change in the IPSS total score from visit 3 (baseline) to visit 7 (end of treatment). Other endpoints; Erectile Function (EF) domain of International Index of Erectile Function (IIEF) Qmax Quality of Erection questionnaire (QEQ) Patient Reported Treatment Impact questionnaire (PRTI) ICIQ-MLUTS questionnaire LUTS diary Population pharmacokinetics;Main Objective: • Compare the efficacy of the 100mg modified release (MR) and 40mg immediate release (IR) formulations of UK-369,003 vs. placebo in men suffering from LUTS with and without ED. • Characterize the dose response relationship of the UK-369,003 modified release (MR) formulation in the treatment of men with LUTS with and without ED. • Investigate the efficacy of UK-369,003 MR doses relative to UK-369,003 40mg IR. • Investigate the efficacy of UK-369,003 MR doses relative to tamsulosin 0.4mg. • To evaluate the safety and tolerability of UK-369,003 in men with LUTS with and without ED. | — |
Countries
Belgium, Czech Republic, Denmark, Finland, Greece, Italy, Latvia, Lithuania, United Kingdom
Outcome results
None listed