E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
sexual function of women with overactive bladder syndrome |
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E.1.1.1 | Medical condition in easily understood language |
sexual function of women with overactive bladder syndrome |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040482 |
E.1.2 | Term | Sexual function abnormal |
E.1.2 | System Organ Class | 100000004872 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
E.1.2 | System Organ Class | 100000004857 |
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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 |
The primary objective is to assess the impact on sexual function, after 12 weeks flexible dose fesoterodine in women with OAB compared to baseline. |
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E.2.2 | Secondary objectives of the trial |
• To assess the use of flexible dosing of fesoterodine on micturition frequency per 24 hours, nocturnal micturitions per 24 hours, urinary urgency incontinence episodes per 24 hours and urgency episodes per 24 hours after 12 weeks compared to baseline.
• To assess the effect of flexible dose fesoterodine on treatment satisfaction and health related quality of life measure at 12 weeks compared to baseline.
• To assess the tolerability of flexible dose fesoterodine in women with OAB.
• To assess the impact of fesoterodine on bowel function.
• To assess if changes in sexual function are independent of urodynamic variables
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female outpatients aged 18 – 80 years.
2. Overactive bladder symptoms (subject reported) for ≥3 months prior to screening visit according to ICS guidelines.
3. Mean number of Urgency episodes ≥3 per 24 hours as verified by the screening bladder diary prior to baseline / Visit 2.
4. Sexually active .
5. Able and willing to complete the micturition bladder diaries and all trial related questionnaires, comply with scheduled clinic visits and clinical trial procedures.
6. Capability of understanding and having signed the informed consent form after full discussion of the treatment and its risks and benefits.
7. Able to speak, read and write in English. |
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E.4 | Principal exclusion criteria |
1. Any condition that would contraindicate the use of fesoterodine including, but not limited to: hyposensitivity to the active substance (fesoterodine fumarate) or any of the excipients, or to peanut, lactose or soya; urinary retention; gastric retention; uncontrolled narrow angle glaucoma; myasthesia gravis; moderate or severe hepatic impairment; severe renal impairment; severe ulcerative colitis; and toxic megacolon.
2. Stage 3 or greater pelvic organ prolapse, defined as tissue protuding to or beyond the introitus in lithotomy position at rest (without increase in intra abdominal pressure).
3. History of lower urinary tract surgery (eg. Incontinence surgery, diverticulectomy, OTIS urethrotomy) with the exception of any minor surgery (eg. Cystoscopic procedures).
4. A known history of interstitial cystitis or a significant pain component associated with OAB symptoms, uninvestigated haematuria, urogenital cancer, interstitial or external radiation to the pelvis or external genitalia, or bladder outlet obstruction, radiation cystitis, genitor-urinary tuberculosis, bladder calculi, urethral obstruction or detrusor-sphincter dysynergia.
5. Subjects with bladder stones. Subjects with a previous history of bladder stones may be included.
6. Previous history of acute urinary retention requiring catheterisation, clinically relevant bladder outlet obstruction or severe voiding difficulties in the judgement of the investigator prior to Visit 2 (baseline).
7. Use of an indwelling or an intermittent self-catheterisation programme.
8. Symptoms of incontinence being predominantly stress urinary incontinence as determined by the investigator.
9. Urinary tract infection (UTI) as shown by the results of the urinalysis at screening or recurrent urinary tract infections (RUTIs) defined as treatment for UTI ≥3 times in the last year.
10. Use of any electrostimulation, bladder training, or pelvic floor exercises (with certified incontinence practitioners) within 4 weeks prior to Visit 1 (Screening).
11. Treatment with antimuscarinic OAB medication with 2 weeks prior to Visit 2 (baseline), including any preparation containing: darifenacin, oxybutynin, propiverine, tolterodine, fesoterodine, solifenacin and trospium.
12. Initiation of treatment during the 12 week trial period with:
a. Any other drug treatment for OAB
b. Any drugs with significant anticholinergic, antispasmodic, parasympathetic, or cholinergic agonistic effects
13. Intermittent or unstable use of diuretics or alpha blockers, or tricyclic antidepressants, oestrogen therapy and any 5AR inhibitors or initiation of such treatment(s) within 2 weeks prior to Visit 2 (baseline).
14. Use of potent CYP3A4 inhibitors, such as grapefruit juice, macrolide antibiotics (erythromycin, clarithromycin), immunosuppressants (cyclosporine), azole antifungal agents (ketonazole, itraconazole), protease inhibitors within 3 weeks prior to Visit 2 (baseline), or the expectation to start any during the trial.
15. Administration of medication capable of inducing hepatic enzyme metabolism or transport (eg rifampicin, carbamazepine, phenytoin, phenobarbital, or St John’s Wort) at any point in the study or within the 6 weeks prior to Visit 2 (baseline).
16. Treatment with potent CYP2D6 inhibitors such as bupropion, cinacalcet, fluoxetine, paroxetine or quinine at any point during the study
17. Participated in any interventional clinical trial or received an investigational drug within 4 weeks prior to Visit 2.
18. History of alcohol abuse and /or any other drug in the opinion of the investigator.
19. Female subjects who are pregnant, nursing, or who are intending to become pregnant during the trial or within three months after the completion of the trial.
20. Female subjects of childbearing potential who are heterosexually active but not using an adequate form of contraception. Reliable contraception methods defined as hormonal methods of contraception (including oral, patches, injected, implants, IUDs, condom with spermicidal foam/gel/film/cream/suppository, tubal ligation male partner who has had a vasectomy for a least 4 months).
21. Subjects who have any medical (including known history of major haematological, renal, cardiovascular or hepatic abnormalities) or psychological condition or social circumstances that would impair their ability to participate reliably in the trial, or those who may increase the risk to themselves or others by participating.
22. Has any current malignancy except
c. Those ≥5 years ago without recurrence
d. Excised basal cell skin carcinoma or squamous cell cancer
23. Subjects who, in the opinion of the investigator, are not likely to complete the trial for any reason.
24. Subjects with an uncontrolled cardiac arrhythmia or congestive heart failure.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in item scores of the Pelvic Organ Prolapse and Urinary Incontinence Sexual Questionnaire – short form (PISQ-12) and the Sexual Quality of Life questionnaire (SQOL) at week 12 relative to baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 12 weeks relative to baseline |
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E.5.2 | Secondary end point(s) |
Bladder Diary
• Change in mean number of micturitions per 24hours at week 12 relative to baseline.
• Change in mean number of nocturnal micturitions per 24 hours at week 12 relative to baseline in subjects with >0 episodes during the 3-day baseline diary period. (Nocturnal micturitions are defined as those occurring between the time the subject goes to bed with the intention of sleeping and the time she rises to start the next day).
• Percentage change in urinary urgency incontinence (UUI) episodes per 24 hours at week 12 relative to baseline in subjects with >0 UUI episodes during the 3-day baseline diary period.
• Change in mean number of urgency episodes per 24 hours at week 12 relative to baseline. (Urgency episodes are defined as those with a Patient Perception of Intensity of Urgency Score (PPIUS) rating of ≥3 in the diary.
• Percentage change in urgency episodes per 24 hours at week 12 relative to baseline.
Subtracted Cystometry (in forty subjects only)
• Change in first sensation
• Change in maximum cystometric capacity
• Change in time to first detrusor contraction
• Presence of detrusor overactivity
Patient Questionnaires
Patient Perception of Bladder Condition (PPBC)
• Change in PPBC at week 12 relative to baseline.
King’s Health Questionnaire (KHQ)
• Change in total score of each domain at week 12 relative to baseline.
Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL)
• Change in total score of each domain at week 12 relative to baseline
Self Assessment Goal Achievement Questionnaire (SAGA)
• Achievement of patient orientated goals at 12 weeks relative to baseline.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 12 weeks relative to baseline |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 4 |
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 | No |
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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End of trial is defined as the last patient's final visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 29 |