E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stress Urinary Incontinence (SUI) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.1 |
E.1.2 | Level | VTc |
E.1.2 | Classification code | 10042213 |
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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 |
To assess the utility of urethral reflectometry in the detection of pharmacologically induced pressure changes in the female urethra.
To compare urethral reflectometry against standard urodynamic assessment of opening and closing urethral pressure using urethral pressure profilometry (UPP) in women with SUI. |
|
E.2.2 | Secondary objectives of the trial |
To assess the effect of [S,S]-Reboxetine on urethral function in women with SUI. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial. 2. Female outpatients aged 18 to 65 years. 3. Clinically significant stress urinary incontinence (SUI) presenting either as pure SUI, or as part of mixed urinary incontinence (MUI) with predominant symptoms of SUI present. 4. Objective evidence of SUI (without concomitant evidence of detrusor overactivity associated with urinary incontinence) as shown by either: - previous evidence of urodynamically proven SUI within 12 months of screening. - or during cystometry performed at the screening visit (as described in section 7.7 of protocol). 5. Subjects must be non-pregnant and non-lactating, and be either postmenopausal (greater than 1 year without menses), surgically sterilized, or using a hormonal contraceptive. (If the subject uses hormonal contraceptives (oral, injected, transdermal or implanted) they must have been using the contraceptive for ≥3 months prior to the study to ensure effectiveness and must remain on the same treatment regime throughout the entire study). Subjects of childbearing potential must have confirmed negative pregnancy tests prior to randomization. 6. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, diary, and other trial procedures. |
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E.4 | Principal exclusion criteria |
1. Symptoms of SUI < 3 months. 2. Presence of nocturnal enuresis. (This will be calculated from the self-reported diary data collected prior to randomization). 3. History of relevant neurological disease (e.g. multiple sclerosis). 4. History of lower urinary tract anatomical anomaly, e.g. clinically significant (grades ≥2) urogenital prolapse. 5. History or evidence of urinary outlet obstruction or urinary retention, including post void residual (PVR) urine volume > 50 ml (on 3 repeated measurements) at Visit 3. 6. Chronic persistent local pathology that may cause urinary symptoms, e.g. interstitial cystitis, genitourinary tumor, bladder stone, recurrent urinary tract infection (UTI) - i.e., 3 or more UTI’s over the past 2 years. 7. Subjects using any pharmacological agent or device for their urinary incontinence (excluding incontinence pads). 8. Subjects with any of the following conditions: i) Indwelling urinary catheters or who perform Intermittent Self Catheterization (ISC). ii) Passive urinary incontinence (eg vesicovaginal fistula). iii) Not capable of independent toileting. 9. Subjects who intend to start a bladder-training program or physiotherapy regimen during the study. Subjects on an established regimen for at least 3 months prior to study start may remain on this as long as it remains unchanged for the duration of the study. 10. Subjects with a documented and untreated urinary tract infection (UTI) at screening. Subjects with a positive (1+ or greater) leukocyte or nitrite result in their urine dipstick test will be excluded unless a UTI can be ruled out via urine culture (please refer to section 7.12 of protocol). Subjects with a documented UTI at screening can undergo a course of treatment. Following treatment, subjects must be asymptomatic and have a repeat negative urine culture. Further participation in the study must be delayed until at least 2 weeks after successful treatment. 11. Subjects with greater than 1+ of haematuria on dipstick test, unless fully investigated prior to randomization to rule out significant urological disease. NB: subjects who are menstruating may be re-screened once menstruation has ceased if they have been found to have haematuria on dipstick testing. 12. History of recurrent syncope or evidence of low blood pressure (BP) (<90mmHg systolic or <40mmHg diastolic). 13. 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 (from sitting). 14. Subjects with a history of transient ischaemic attacks (TIA’s), stroke, or the presence of a carotid bruit (unless significant carotid stenosis (>70%) has been ruled out by appropriate investigation). 15. Narrow angle glaucoma. 16. Major depressive disorder (as defined by DSM-IV diagnostic criteria – see Appendix 2 of the protocol). 17. Subjects receiving prohibited concomitant medications such as antidepressants, MAOI’s, CYP3A4 inhibitors and antimuscarinics (Further details can be found in section 5.5 of the protocol). 18. Subjects who require systemic or topically applied Hormone Replacement Therapy (HRT) must have been using this at a stable dose for at least 3 months prior to study entry. Any change in dose or type of HRT taken during the study will be considered a protocol violation. 19. Subjects taking any medication for an unlicensed indication. 20. Creatinine clearance ≤ 30 ml/min (see section 7.12 of protocol). 21. Subjects with significant hepatic impairment (moderate, i.e., Child-Pugh score of 7 to 9, and severe, i.e., Child-Pugh score of 10 to 15– see Appendix 1 of the protocol). 22. Clinically significant abnormal 12-lead ECG taken at screening e.g. evidence of heart block or other cardiac arrhythmias (see Appendix 3 of the protocol). 23. Malignancy within the past 2 years with the exception of basal cell carcinoma. 24. Subjects with a history of alcohol or drug abuse in the past 2 years 25. Subjects who are unable to swallow oral medication (tablets). Tablets are not to be crushed. 26. Subjects who in the opinion of the investigator, or that of the Pfizer clinician, are unable and/or unlikely to comprehend the nature, scope and possible consequences of the study and to follow the study procedures and instructions and complete all study related measurements. This includes poor compliance with the trial medication, and subjects who demonstrate uncooperative behavior. 27. Hypersensitivity to, or previous intolerance of, [S,S]-Reboxetine, racemic reboxetine, other norepinephrine re-uptake inhibitors. 28. Intention to donate blood / blood products during the study or up to one month after completion of the study. 29. Recent (up to 30 days or 5 x half life, whichever is longer) receipt of any other investigational drug. 30. Subjects judged clinically to be a serious suicidal risk. 31. Subjects who have a history of a seizure disorder. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Opening urethral pressure (Reflectometry) |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |