E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stress urinary incontinence |
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MedDRA Classification |
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 evaluate efficacy of treatment with PSD503 compared with placebo in female volunteer patients with Stress Urinary Incontinence (SUI) as measured by the change in pad weight gain following the exercise stress pad test at pre-dose compared to the pad weight gain following the exercise stress pad test post-dose administration.
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E.2.2 | Secondary objectives of the trial |
To evaluate: • plasma concentrations of PSD503 in female volunteer patients with SUI at 1 and 3 hours after dose administration. • changes in blood pressure and pulse after treatment with PSD503 compared with placebo in female volunteer patients with SUI over 3 hours after dose administration. • safety and tolerability of PSD503 compared with placebo in female volunteer patients with SUI.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A subject will be invited to participate if she meets the following inclusion criteria: 1. Is willing and able to provide written informed consent 2. Is female and aged 18–75 years inclusive 3. Has SUI confirmed by a urinary (cough) stress test and urodynamic assessment within 36 months of Screening 4. Has a SUI episode frequency ≥7 and ≤21 per week confirmed by a Frequency Volume Chart (FVC). If the subject has not completed a FVC prior to Screening, the subject will be asked to complete a FVC for a minimum of 3 days and to return this on Treatment Day 1 5. Has normal filling cystometry conducted as part of a urodynamic assessment within 36 months of Screening (a bladder filling capacity of ≥300mL and a first sensation of filling >100mL)
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E.4 | Principal exclusion criteria |
A subject will be excluded from study participation if she meets any of the following criteria: 1. Has predominantly symptoms of urge urinary incontinence (>10 voids / 24 hours; >1 nocturia / night; urgency; urge incontinence) confirmed by a FVC. If the subject has not completed a FVC prior to Screening, the subject will be asked to complete a FVC for a minimum of 3 days and to return this on Treatment Day 1 2. Has detrusor overactivity and / or a post-void residual volume >150mL diagnosed by urodynamic examination within 36 months of Screening 3. Is unable to perform the physical exercises as required by the exercise stress pad test in the opinion of the Investigator 4. Has a current or past history of any cardiac abnormality or disease, or tachycardia, or any clinically significant abnormality in the opinion of the Investigator on electrocardiogram (ECG) at Screening 5. Has a current or past history of hypertension (systolic blood pressure [SBP] ≥140mmHg or a diastolic blood pressure [DBP] ≥90mmHg). (If the subject has a SBP ≥140mmHg or a DBP ≥90mmHg on admission on any Treatment Day then they must be withdrawn) 6. Has any significant medical history, including a current history of hyperthyroid disease, glaucoma, asthma or insulin dependent diabetes mellitus 7. Has a current or past history of (a) atherosclerotic disease including ischaemic heart disease, stroke, transient ischaemic attacks or with known aneurysm(s) or (b) vasospastic diseases e.g. Raynaud’s phenomenon and migraine 8. Has a known hypersensitivity to phenylephrine or any component in the preparation of PSD503 or has a known intolerance to sympathomimetics 9. Has received within the 4 weeks prior to Screening or is continuing to receive any treatment which could: a) interact with phenylephrine (antihypertensives, atropine, monoamine-oxidase inhibitors [MAOIs], tricyclic antidepressants, selective serotonin reuptake inhibitors [SSRIs], serotonin / noradrenaline reuptake inhibitors [SNRIs], cyclopropane, halothane, sympathomimetics, cardiac glycosides, quinidine, doxapram, oxytocin, ergotamine, methysergide, dopexamine and entacapone) b) contain phenylephrine and related substances (e.g. Sudafed and Contac) c) cause phenylephrine-like side-effects 10. Has received or is continuing to receive any treatment for SUI in the 4 weeks prior to Screening. (Subjects who have consistently performed Kegel exercises for at least 4 weeks prior to Screening and are committed to continue to perform them regularly throughout the study may participate) 11. Has a urogenital prolapse >grade 1, cystocele, or has a previous history resulting in scarring in the pelvic region (e.g. surgery / radiotherapy) 12. Has a history of recurring proven urinary infections (i.e. more than 2 in past year) or cystitis or is known to be suffering from any sexually transmitted disease 13. Is lactating, or pregnant or at risk of pregnancy during the study. The subject must be either using secure contraceptive precautions, or have been surgically sterilised or be post-menopausal (defined as at least two years since the last menstrual period) 14. Has a history of alcohol or drug abuse 15. Has any clinically significant findings on urinalysis, chemical pathology, physical examination, vital signs or clinically significant concurrent illness at Screening that in the opinion of the Investigator precludes inclusion / further participation in the study 16. Has participated in a clinical trial within 30 days of Screening 17. Is unable to read and / or understand English 18. Is unwilling or unable to abide by the protocol or in the opinion of the Investigator, a subject who is not likely to complete the study for any reason
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage change in pad weight gain from pre-dose to that post-dose administration following the exercise stress pad test
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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 | No |
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 | 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
| 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 | 8 |
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 | 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
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As this is a 2-way cross-over study, subjects will receive each treatment once |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |