E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Overactive Bladder Syndrome |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
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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 quantify the extent of symptomatic relief provided by 20, 40, 80 and 120 mg SMP 986 (o.d) following 8-weeks of treatment in patients with OABS |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of 20, 40, 80 and 120 mg SMP 986 (o.d) following 8-weeks of treatment in patients with OABS
To determine the most clinically appropriate dose range for SMP-986 in terms of treatment benefit (efficacy, safety, tolerability and QOL outcomes) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for inclusion patients must:
1. Have given written informed consent to participate in the study
2. Be >= 20 - <= 80 years of age (at screening). Female subjects must be post-menopausal as defined by the following criteria: • Either >= 12 months of spontaneous amenorrhea or >= 6 - <= 12 months of spontaneous amenorrhea with FSH levels within the post menopausal range as determined by the central laboratory Or • Surgically sterile
3. Have a documented diagnosis of OABS based on symptomatic reporting of urinary frequency and urgency (with or without urgency incontinence) over a successive period of >= 6 months prior to screening
4. Have had an average of >= 8 micturition episodes/ 24 hrs during the 3 days prior to randomisation
5. Have experienced >= 3 episodes of urgency with or without urgency incontinence during the 3 days prior to randomisation |
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E.4 | Principal exclusion criteria |
Patients are not eligible for this study if they fulfil any of the following criteria:
1. Have a cardiac arrhythmia that requires treatment
2. Have a post-void residual volume >150 mL at screening
3. Have a maximum urine flow rate of <15mL/s at screening or at visit 2 (applicable to male patients only)
4. Have, or have had, a medical condition contraindicating the use of antimuscarinics (e.g. untreated narrow angle glaucoma, uncontrolled open angle glaucoma, xerostomia, myasthenia gravis) or a known hypersensitivity to anti-cholinergics
5. Have not discontinued use of the following prohibited medications from >= 14 days prior to randomisation: any drugs used to treat OABS or urinary incontinence, cholinergics, anti cholinergics, alpha adrenergic antagonists, opioid analgesics, compound analgesics containing an opioid, warfarin or other substrates of cytochrome P450 2C9 which have a narrow therapeutic index, potent cytochrome P450 3A4 and 2D6 inhibitors or inducers
6. Are not willing or able to complete a study diary during the 8-week study (patients capabilities’ in this respect will be assessed by the clinical site staff using patients’ diary data from the placebo run-in phase)
7. Have a drug compliance of <= 80 % for the placebo run-in period
8. Continued use of the following prohibited treatments from >= 14 days prior to screening: electro-stimulation therapy for OABS, bladder training programme if not stabilised before screening
9. Have an indwelling catheter or perform intermittent self catheterisation
10. Have participated in another clinical trial with an investigational drug within 8 weeks prior to randomisation
11. Have polyuria (a documented medical history and/or a study diary recording of an average of >= 3L urine passed/ 24 hrs during the 3 days prior to randomisation)
12. Have stress urinary incontinence or mixed urinary incontinence for which stress is the predominant factor
13. Have a neurological cause of OABS symptoms e.g. multiple sclerosis, Parkinson’s disease, full or partial spinal cord injury
14. Have painful bladder syndrome/interstitial cystitis, bladder stones or a symptomatic calculous disease (e.g. kidney stones) affecting the lower urinary tract
15. Have poorly controlled diabetes as indicated by an HbA1c result of >7% at screening
16. Have a documented past medical history of peripheral, autonomic or diabetic neuropathy
17. Have ever received any specialist pharmacological treatment for OABS e.g. treatment with botulinum toxin A, resiniferatoxin or capsaicin
18. Have a urinary tract infection (UTI) or, have had proven diagnoses of >= 3 episodes of UTI within the 12 months prior to screening
19. Have, or have had a malignancy with or without metastases within the last 5 years or have ever had a tumour (malignant or benign- but not including benign prostatic hyperplasia) affecting the genitourinary tract
20. Have had genitourinary surgery or lower bowel surgery within the 12 months prior to screening or have ever received pelvic radiation
21. Have >= stage 2 pelvic organ prolapse (as defined by the ICS pelvic organ prolapse quantification system)
22. Concomitant use of hormone replacement therapy or diuretics if the dose has not been stable for a period of >= 12 weeks prior to screening
23. Have, in the opinion of the Investigator, a significant history of constipation or have an active bowel disease (e.g. inflammatory bowel disease, colitis, diverticulitis)
24. Have any other clinically significant cardiac, neurological, hepatic, renal, respiratory, or haematological disorders, or any other illness (including any psychiatric disorder) which in the opinion of the Investigator would preclude the safe or compliant participation of a subject
25. Have ongoing, or a history of, known or suspected drug and/or alcohol abuse
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from baseline to week 8 in mean number of voids/24 hrs |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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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The end of the study is defined as the last patient undergoing the last visit of the study. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |