| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Storage male lower urinary tract symptoms (LUTS) with and without erectile dysfunction (ED). |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10046566 |
| E.1.2 | Term | Urinary tract disorder |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Estimate the efficacy of UK-369,003 MR versus placebo for the treatment of storage
male LUTS with and without ED. |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of UK-369,003 in men with storage LUTS with and without ED.
• Characterize the dose response relationship of UK-369,003 in men with storage LUTS with and without ED. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male subjects aged 18 years and above, with documented clinical diagnosis of OAB as verified by the screening LUTS diary defined by:
• Mean urinary frequency ≥8 times /24 hours.
• Mean number of urgency episodes, with or without urgency incontinence ≥1 episode /24 hours.
2. Mean voided volume <300 ml as verified by the bladder diary completed prior to
randomization.
3. Qmax >5 ml/sec with a voided volume >150 ml.
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 aspects of the trial.
6. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests and other trial procedures. |
|
| E.4 | Principal 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 screening visit or during the course of the trial.
2. Post-void residual urine volume >200 ml based on bladder ultrasound at screening visit.
3. Documented urinary tract infection (UTI) at screening visit; 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 screening visit, unless fully investigated prior to randomization (baseline visit) to rule out significant urological disease.
5. 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 at baseline visit).
6. 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).
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 screening visit (includes intermittent self-catheterization).
9. Use of any electrostimulation or bladder training in the past 30 days or who are expected to start such treatment during the study.
10. Subjects with a total volume voided of > 3000 ml on average per 24 hours, as confirmed by the LUTS diary completed prior to randomization.
11. Subjects receiving or who are likely to receive any of the following medications or
treatments during the trial period:
• α-blockers, muscarinic receptor antagonists, PDE5 inhibitors, and agents known to
affect vesico-urethral function or erectile function (including vacuum devices). Such
treatments must be terminated at least four weeks prior to randomization at baseline visit and must not be taken at any time during the trial.
• 5-α-RIs (unless at stable dose for six months prior to randomization at baseline visit, and stable dose maintained through duration of the trial).
• Diuretics, beta-blockers or other anti-hypertensive agents (unless stable for four
weeks prior to visit 3 (baseline) and stable dose maintained throughout the duration of the trial).
• Nitrates or nitric oxide donors in any form on either regular or intermittent basis (oral, sublingual, buccal, transdermal, inhalation or aerosols).
• Potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, miconazole,
clotrimazole, nefazadone, clarithromycin, troleandomycin, ritonavir and saquinavir).
Topical agents are permitted.
• Warfarin.
12. Significant allergy to or known hypersensitivity or intolerance to PDE5 inhibitors or any of the excipients in the formulation.
13. Increased susceptibility to vasodilators including those subjects with left ventricular outflow obstruction (e.g., hypertrophic obstructive cardiomyopathy).
14. Poorly controlled type I or type II diabetes mellitus as defined by HbA1C >7% at
screening visit.
15. Loss of vision in one eye due to non-arteritic ischemic optic neuropathy (NAION)
regardless of whether or not this event was temporally associated with the use of a PDE5 inhibitor.
16. Hereditary degenerative retinal disorders (e.g. retinitis pigmentosa).
17. History of recurrent syncope or evidence of low blood pressure (BP) (<90 mmHg systolic or <40 mmHg 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).
18. Any relevant clinically significant abnormalities on the Screening visit physical
examination or laboratory tests including subjects with moderate liver function tests
abnormalities (>1.5 times the upper limit of normal) and renal function abnormalities
(serum creatinine ≥2.5 mg/dl or ≥220 µmol/l).
19. 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.
20. Risk of priapism e.g. sickle cell disease, multiple myeloma and myeloproliferative
disorders (e.g. myeloid leukemia, polycythemia, thrombocythemia).
21. 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.
22. Any malignancy not considered cured (except basal cell carcinoma of the skin).
Exclusion criteria 23, 24 and 25 are not listed due to limitation of characters. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. LUTS diary:
a. Mean voided volume
b. Urgency episode frequency
c. Severity of urgency episodes
d. Micturition frequency.
e. Normalized micturition frequency (NMF)
f. Incontinence episode frequency
g. Micturition episodes associated with urgency
h. Nocturnal frequency
2. International Prostate Symptom Score (IPSS)
3. Overactive Bladder questionnaire – Short Form (OAB-q SF)
4. Patient Perception of Bladder Condition (PPBC)
5. International Consultation on Incontinence Questionnaire – Male Lower
Urinary Tract Symptoms (ICIQ-MLUTS)
6. Erectile Function (EF) domain of International Index of Erectile Function
(IIEF)
7. Quality of Erection questionnaire (QEQ)
8. Patient Reported Treatment Index questionnaire (PRTI)
9. Population Pharmacokinetics |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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