A MULTI-CENTER, RANDOMIZED, CROSS-OVER, DOUBLE-BLIND, THIRD PARTY OPEN, PLACEBO CONTROLLED, PILOT STUDY TO ASSESS THE URODYNAMIC EFFECTS OF MODIFIED RELEASE UK-369,003 IN MEN WITH LOWER URINARY TRACT SYMPTOMS (LUTS)

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 20

Inclusion Criteria

*Male subjects, aged 40 years and above, with documented LUTS with an International Prostate Symptom Score =13 at both screening and baseline visit.
*Clinical diagnosis of BPH
*Qmax 5 to 15 ml/sec with a voided volume of >150 ml at screening visit.
*Urodynamically defined bladder outlet obstruction based on bladder outlet obstruction index >40; calculated as PdetQmax –2Qmax and measured at visit 2 (baseline).
*A minimum of 50% of the patient population will also have urodynamically confirmed DO (an involuntary detrusor contraction of = 10cm H2O during baseline filling cystometry and volume to first contraction = 350ml)
*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 aspects of the trial.
*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

*History, evidence or suspicion of prostate cancer (includes total PSA value > 10 ng/ml unless prostate cancer previously excluded by biopsy)
*Post-void residual urine volume >200 ml based on bladder ultrasound at screening
*Documented UTI; 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.
*Greater than 1+ of hematuria on dipstick test, unless fully investigated prior to randomization to rule out significant urological disease.
*History of relevant urological surgery or procedures that may contribute to LUTS (e.g. prostatectomy, bladder neck surgery, minimally invasive procedures of the prostate, prostatic stent insertion, pelvic irradiation, cystoscopy < 30 days prior to randomization)
*Chronic persistent local lower urinary tract pathology (e.g. bladder neck contracture, prostatitis, bladder stone, cystitis, urethral stricture, carcinoma, large bladder diverticulum, recurrent gross hematuria).
*Known primary neurological condition such as multiple sclerosis, Parkinson’s disease, or other neurological diseases known to affect bladder function.
*History of catheterization for outflow obstruction in the previous 12 month (includes intermittent self-catheterization).
*Subjects with history of difficult catheterization.
*Subjects receiving or who are likely to receive during the study any of the medications:
• a-blockers, muscarinic receptor antagonists, PDE5 inhibitors, and agents known to affect vesico-urethral function.
• 5-a-RIs
• Diuretics, beta-blockers or other anti-hypertensive agents
• Nitrates or nitric oxide donors in any form on either regular or intermittent basis (oral, sublingual, buccal, transdermal, inhalation or aerosols).
• Potent CYP3A4 inhibitors
• Topical agents are permitted.
• Warfarin.
*Significant allergy to or known hypersensitivity or intolerance to PDE5 inhibitors.
*Increased susceptibility to vasodilators including those with left ventricular outflow obstruction (e.g., hypertrophic obstructive cardiomyopathy)
*Poorly controlled type I or type II diabetes mellitus as defined by Hemoglobin A1C >7%.
*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.
*Hereditary degenerative retinal disorders (e.g. retinitis pigmentosa).
*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.
*Any relevant clinically significant abnormalities on the screening physical exam or laboratory tests including patients with moderate liver function tests abnormalities (>1.5 x upper limit of normal) and renal function abnormalities (serum creatinine =2.5 mg/dl or =220 µmol/l).
*Family history of prolonged QT syndrome or who themselves have a QTc of >450msec at the screening visit as measured by a 12-lead supine ECG.
*Risk of priapism e.g. sickle cell disease, multiple myeloma and myeloproliferative disorders (e.g. myeloid leukemia, polycythemia, thrombocythemia).
*Subjects currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the study, or to comply with the requirements of the protocol, including: dermatolo

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials