E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 evaluate the efficacy of twice daily dosing with 2 doses of XEN-D0501 on the urinary symptoms of subjects with OAB compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
To determine the safety and tolerability of twice daily dosing with 2 doses of XEN-D0501 in subjects with OAB compared to placebo. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetics sub-study |
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E.3 | Principal inclusion criteria |
1. Willing and able to give written, informed consent 2. Females, 40-80 years of age. If under 60 years of age, subjects must not be of child bearing potential (i.e., postmenopausal [defined as amenorrheic for at least 1 year (off hormone replacement therapy) AND have a serum follicle-stimulating hormone (FSH) level of at least 30 IU/L at Visit 1], or have undergone a hysterectomy or bilateral oophorectomy, or have other documented evidence of infertility. Note: Tubal ligation is not acceptable) 3. A current primary diagnosis of OAB (in accordance with International Continence Society [ICS] guidelines) with medical history indicating a mean of ≥ 8 voids/day and 1 or more episodes of urgency or incontinence/day 4. Evidence of frequency in combination with moderate to severe urgency episodes from the Placebo Run-in Period micturition diary, with a mean of ≥ 8 voids/day and a total of ≥3 episodes of moderate to severe urgency or incontinence during the 3 day urinary diary period before randomisation at Visit 2 5. Body mass index (BMI) between 18 and 32 kg/m2 6. Agree to refrain from blood donation during the course of the study 7. Agree to stop taking any existing medication that may interfere with study evaluation (e.g. diuretics, antimuscarinics, potent CYP3A4 inhibitors and antidepressants) from the start of Placebo Run-in Period to the final Follow-up Visit. |
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E.4 | Principal exclusion criteria |
1. Clinically significant unstable medical condition (other than idiopathic OAB) that might in the Investigator’s opinion interfere with assessment or follow-up 2. History or evidence of urinary retention or bladder outlet obstruction (defined as post-void residual volume >50mL or uroflow rate <15mL/sec with a void volume at least 120 ml) 3. Current (within past 3 months) bladder pain 4. History of QTc prolongation or QTc interval ≥470 msec at Visit 1 5. Predominant stress urinary incontinence versus urge urinaryincontinence based on subject history (e.g. exclude patients whose predominant symptoms are incontinence related to cough, sneezing, straining, etc.) 6. Neurogenic bladder (e.g. associated with spinal cord injury, multiple sclerosis) 7. Anatomic or structural abnormalities possibly causing urinary urgency or incontinence 8. Surgery on the lower urinary tract within previous 3 months of the baseline assessment (Visit 1) 9. History of ≥4 urinary tract infections (UTIs), interstitial cystitis or haematuria of unknown cause, or use of indwelling catheter in the previous 12 months or a current diagnosis of UTI as determined by the investigator; 10. Electro-stimulation therapy or starting bladder training or physiotherapy for bladder control within previous 2 weeks of Visit 1 11. Scheduled surgery or procedure during the study period 12. History (within previous 1 year of consent) of alcohol or substance dependence (except nicotine dependence) according to Diagnostic and Statistical Manual of Mental Disorders (DSM IV TR) criteria 13. History of any kind of cancer within the last 5 years unless non-invasive, in remission and approved in writing by Sponsor 14. Existing non-malignant tumours that could compromise the function and/or anatomy of the lower urinary tract 15. Urine output >3.0L/day 16. Concomitant disease or condition (or its treatment) which could interfere with the conduct of the study, or which would in the opinion of the Investigator, pose a risk to the subject in this study 17. Participation in an investigational drug or device study within 30 days prior to Visit 1 or within 5 half lives of the drug, whichever is the greater. 18. Botulinum toxin treatment within previous 9 months of Visit 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Change from baseline to the last on-treatment evaluation visit in the number of voids/24hrs (mean of the three days prior to the last on-treatment visit). |
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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 | 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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Single blind placebo run-in phase |
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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 | Yes |
E.8.2.3.1 | Comparator description |
2 mg XEN-D0501 versus 4 mg XEN-D0501 versus Placebo |
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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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
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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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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 | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |