| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subjects with overactive bladder syndrome with urinary urge. |
|
| 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 |
| Comparison of 180 mg b.i.d. NS-8 versus placebo regarding primary efficacy variable (change in mean number of incontinence episodes within 3 days before Day 56 versus baseline). |
|
| E.2.2 | Secondary objectives of the trial |
1. Assessment of dose-relationship regarding primary efficacy variable.
2. Comparison of 240 mg b.i.d. NS-8 and 120 mg b.i.d. NS-8 versus placebo regarding primary efficacy variable;
3. Comparison of 180 mg b.i.d. NS-8, 240 mg b.i.d. NS-8 and 120 mg b.i.d. NS-8 versus active control regarding primary efficacy variable;
4. Comparison of efficacy of 120, 180 and 240 mg b.i.d. NS-8 versus placebo and active control regarding the secondary efficacy variables;
5. Comparison of safety and tolerability of NS-8 versus placebo and active control;
6. Assessment of variability and linearity of NS-8 trough levels in blood.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Subjets with overactive bladder will be enrolled in this trial and randomised only if they meet all of the following criteria:
1. Are able to provide written informed consent;
2. Are minimum or older than 18 years of age;
3. Have at least 2 incontinence episodes within 3 days before Day 0;
4. Have at least 8 micturitions per 24 hours (mean of last 3 days before Day 0);
5. Females must not be pregnant or plan to become pregnant during the trial.
Females with childbearing potential must provide a negative urine pregnancy test at Visits 1 and 2 and must be using an appropriate method of contraception |
|
| E.4 | Principal exclusion criteria |
Patients will be enrolled in this trial only if they meet none of the following criteria:
1. Stress incontinence (involuntary loss of urine during coughing, sneezing, going upstairs or change of position); Note: A patient with mixed incontinence can be enrolled if urge incontinence is the predominant symptom of the patient's incontinence.
2. Intermittent catheterisation;
3. Neurogenic bladder dysfunction, spina bifida, quadriplegia, multiple sclerosis;
4. Benign prostatic hypertrophy syndrome with a significant degree of bladder outflow obstruction resulting in post-void residual urine ≥100 mL;
5. Females and males with post-void residual urine ≥100 mL;
6. Interstitial cystitis;
7. Single voided micturition volume >400 mL;
8. Mean volume per micturition within 24 hours >300 mL;
9. Mean voided volume >3 L within 24 hours;
10. Acute urinary tract infection within 7 days before and during randomisation proven by urinalysis and urine culture;
11. Chronic urinary tract infection (³105 bacteria/mL urine);
12. Electrostimulation therapy if performed within 4 weeks before Visit 1;
13. Anomalies of the lower genitourinary tract (e.g., fistulas, urethral or meatal stenosis, severe prolapse);
14. Radiation bladder, bladder calculi, urethral calculi, untreated bladder carcinoma;
15. Operations of the lower genitourinary tract within the last 6 months (e.g., Transurethral Prostatic Surgery [TUR-P] or total prostatectomy, bladder tumour operation, operative intervention for incontinence);
16. Have a progressive fatal disease/life expectancy of less than 5 years;
17. Have severe disease likely to jeopardise the planned completion of the trial (e.g., cancer, cardiac infarct, unstable angina pectoris);
18. Have impaired hepatic function
19. Diabetes insipidus;
20. Pre-existing medical contraindications for COX-inhibitors;
21. Tachyarrhythmia, hypotension;
22. Patients with QTc prolongation (QTc >500 ms) and patients with risk factors for QTc prolongation, e.g., cardiac insufficiency, hypokalaemia, congenital QT-long-syndrome as well as intake of medications with a potential to prolong the QTc interval;
23. History of, or known current problems with, drug or alcohol abuse;
24. Concomitant medication known to have a potential to interfere with the trial medication (see section 5.7.2);
25. Are likely to require treatment during the trial with drugs not permitted by the trial protocol (see section 5.7.2)
26. Known hypersensitivity to NS-8, oxybutynin or excipients contained in the trial medication;
27. Pregnant or nursing women, or women of childbearing potential without reliable contraceptive method;
28. History or suspicion of unreliability, poor co-operation or non-compliance with medical treatment;
29. Patients who are not able to swallow the largest capsule;
30. Any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the trial;
31. Have received treatment with any other investigational drug in the last 30 days before Visit 1.
32. Have previously been enrolled in this trial.
33. Patients with contraindications to the use of oxybutynin;
34. Patients with untreated or suboptimally treated thyroid diseases manifested by clinically relevant abnormal blood concentrations of thyroid hormones (TSH, T3, thyroxine [T4]);
35. Patients with a history of sensitivity to photosensitising drugs (e.g., psoralen, tetracyclines, St. Johns Wort) displayed as photoallergies or phototoxicities;
36. Patients taking CYP?3A4 inhibitors |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Number of incontinence episodes within 3 days before Day 56, change versus baseline. |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 | 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) | Yes |
| 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.8.5 | 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 | 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 |
|
| 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
|
| The entire trial will terminate after the last visit of the last patient. The sponsor can terminate the entire trial prematurely if an unexpected, significant, or unacceptable risk to the patients is discovered or if they decide to suspend or discontinue development of NS-8 for medical reasons. |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 6 |
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