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 | 9.1 |
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 assess efficacy, safety and tolerability of three different, repeated oral doses of netupitant in patients with symptoms of OAB |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female patients ≥ 18 years old 2. Symptoms of overactive bladder for at least 6 months before entering the run-in, single-blind treatment period 3. Able to read, understand and follow the study procedures and complete OAB diary 4. Willing and able to sign informed consent 5. If female, they must be either post-menopausal for at least 12 months or surgically sterilized. In case of fecund women, they must use a reliable method of contraception such as a combination of spermicidal / barrier method (condom, sponge, foam, jelly, or diaphragm) or intrauterine devices which do not involve the use of steroid hormones. 6. Baseline 3 day diary (to be recorded during the last three days before visit # 2), reporting ≥ 3 urgency episodes, with or without ≥ 3 incontinence episodes, and with 10-20 micturitions/24 hours
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E.4 | Principal exclusion criteria |
1. Breast feeding 2. Grade III/IV pelvic organ prolapse with or without cystocele 3. History of pelvic prolapse repair (cystocele or rectocele) or urethral diverticulectomy within 6 months of screening 4. Stress incontinence or mixed incontinence where the stress incontinence prevails 5. Urinary incontinence due to causes other than overactive bladder 6. Nocturnal enuresis only 7. Residual urinary volume > 200 ml measured by ultrasound 8. Current repeated Urinary Tract Infections (UTIs): > 4 episodes/year 9. Bladder cancer 10 History of unstable angina and/or congestive heart failure 11. History or predisposition to cardiac conduction abnormalities 12. History of risk factors for Torsade de Point (heart failure, hypokalemia, family history of Long QT Syndrome) 13. History of radiation cystitis or history of pelvic irradiation 14. Electro-stimulation, biofeedback, bladder training therapy (behavioral therapy) within 3 months of the screening visit and/or during the study 15. Investigational treatments within 30 days of start of run-in 16. Any neurological disease that may affect bladder function or muscle strength 17. Chronic alcohol or drug abuse 18. Diabetes insipidus 19. Diabetes mellitus type I or II with peripheral neuropathy and/or polyuria 20. Previous or concomitant local administration of botulinum toxin in the lower urinary tract 21.Chronic inflammatory bowel diseases such as Chron’s Disease and ulcerative colitis 22. Previous or concomitant treatment with NK1 receptor antagonists 23. Known contra-indications to NK1 receptor antagonists 24. Concomitant treatment with anti-muscarinic drugs. Patients on treatment with anti-muscarinic drugs and willing to participate will need to stop their administration from visit 1 throughout the study duration, including visit # 7. 25. Neoplastic disorder which is either active or has been in remission for less than one year 26. Chronic use of any CYP 3A4 substrates or inhibitors (e.g. terfenadine, cisapride, astemizole, clarythromycine, ketoconazole or itraconazole) 27. Chronic use of any CYP 3A4 inducers (e.g. barbiturates, rifampicin, rifabutin, phenytoin, or carbamazepine) 28. History or current diagnosis of HIV, or of any type of viral hepatitis 29. Concomitant use of α-blockers, α-adrenergic agonists, unless given at stable doses for at least 3 months of the screening visit and remaining stable throughout the study duration 30.Pregnancy 31. Polyuria (diuresis > 3 L/24 hours) 32. History of interstitial cystitis or bladder related pain 33. Any local pathology that might cause bladder symptoms 34. Severe, uncontrolled arterial hypertension or myocardial infarction < 3 months, congestive heart failure, active coronary artery disease 35. Use of concomitant medications that prolong the QT/QTc interval 36. History of any illness that, in the opinion of the investigator, may confound the results of the study or pose unwarranted risk in administering the study drug to the patient 37. Concomitant diseases likely to interfere with the study drug (capable of altering absorption, metabolism or excretion 38. Marked baseline prolongation of QT/QTc interval [QTc >460 msec]; QRS > 110 msec; PR > 240 msec; HR < 55 bpm; atrial fibrillation; complete left bundle branch block. For this purpose, the ECG performed at screening visit will be assessed. 39. Abnormal laboratory values including: a. AST (Aspartate Aminotransferase) > 2.5 x Upper Limit of Normal b. ALT (Alanine Aminotransferase) > 2.5 Upper Limit of Normal c. Bilirubin > 1.5 x Upper Limit of Normal d. Creatinine > 1.5 x Upper Limit of Normal |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage change from the baseline in the average number of daily micturitions (primary) at week 8. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |