E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Overactive Bladder |
Sindrome della vescica iperattiva. |
|
E.1.1.1 | Medical condition in easily understood language |
Overactive Bladder |
vescica iperattiva |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Physical Phenomena [G01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
E.1.2 | System Organ Class | 100000004857 |
|
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 safety and tolerability of long-term combination treatment of solifenacin (5 mg) with mirabegron (50 mg) compared to solifenacin and mirabegron monotherapy in subjects with overactive bladder (OAB) |
Valutare la sicurezza e la tollerabilità a lungo termine del trattamento combinatoa base di solifenacina (5 mg) e mirabegron (50 mg) rispetto alla monoterapia di solifenacina e mirabegron nei soggetti con vescica iperattiva. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate efficacy of long-term combination treatment with solifenacin and mirabegron
To evaluate Patient Reported Outcomes (PRO) during long-term combination treatment with solifenacin and mirabegron
|
Valutare l’efficacia a lungo termine del trattamento combinatoa base di solifenacina e mirabegron
Valutare i PRO (Patient Reported Outcomes) a lungo termine deltrattamentocombinatoa base di solifenacina e mirabegron
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject is male or female and at least 18 years of age;
• Subject is willing and able to complete the micturition diary and questionnaires correctly and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings;
• Subject has symptoms of “wet” OAB for at least three months |
- Il soggetto è di sesso maschile o femminile, e di almeno 18 anni di età.
- Il soggetto è disposto ed è in grado di compilare il diario sulla minzione e i questionari correttamente, ed è in grado di misurare i propri segni vitali a casa alle scadenze convenute, utilizzando il dispositivo fornito dal personale dello studio, e di registrare correttamente le letture.
- Il soggetto ha sintomi di OAB "bagnata" da almeno 3 mesi. |
|
E.4 | Principal exclusion criteria |
• Subject has neurological cause for detrusor overactivity (e.g.
neurogenic bladder, diabetic neuropathy or systemic or central
neurological disease such as multiple sclerosis and Parkinson's disease).
• Subject has chronic inflammation such as bladder pain syndrome /
interstitial cystitis, symptomatic bladder stones or any previous or
current radiation cystitis.
• Subject has moderate to severe hepatic impairment
• Subject has severe renal impairment
• Subject has a clinically significant abnormal ECG
• Subject has a concurrent malignancy or history of cancer (except
noninvasive skin cancer) within the last 5 years prior to screening.
• Subject has a QTcF interval > 450 ms for males or > 470 ms for
females or is at risk of QT prolongation (e.g., family history of long QT
syndrome, hypokalaemia).
• Subject has severe hypertension, which is defined as a sitting
average systolic blood pressure ≥ 180 mmHg and/or average diastolic
blood pressure ≥ 110 mmHg.
• In the opinion of the investigator the subject has clinically significant bladder outflow obstruction at risk of urinary retention;
• Subject has significant PVR volume (> 150 mL);
• Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator;
• Subject has an indwelling catheter or practices intermittent self-catheterization;
• Subject has evidence of urinary tract infection (UTI), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
• Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin; |
- Il soggetto presenta una causa neurologica di iperattività detrusoriale (per es. vescica neurogena, neuropatia diabetica o malattia neurologica sistemica o centrale come sclerosi multipla e morbo
di Parkinson).
- Il soggetto presenta un’infiammazione cronica come per esempio sindrome della vescica dolorosa/cistite interstiziale, calcoli vescicali sintomatici o qualunque forma presente o passata
di cistite da radiazioni.
- Il soggetto è affetto da compromissione epatica da moderata a grave.
- Il soggetto è affetto da compromissione renale grave.
- Il soggetto presenta un ECG non nella norma in modo clinicamente significativo.
-Il soggetto è affetto o è stato affetto da una patologia maligna o tumore ( ad eccezione del tumore della pelle) nei 5 anni precedenti lo screening.
- Il soggetto ha un intervallo QTcF > 450 ms nel caso di pazienti di sesso maschile o > 470 ms nel caso di pazienti di sesso femminile o è a rischio di prolungamento dell’intervallo QT (per es. anamnesi familiare che presenta sindrome del QT lungo, ipocalemia).
- Il soggetto è affetto da ipertensine grave, definita come pressione sistolica media rilevata in posizione seduta ≥ 180 mmHg e/o pressione arteriosa diastolica media ≥ 110 mmHg.
- A parere del ricercatore, il soggetto presenta un’ostruzione del flusso urinario clinicamente significativa, con rischio di ritenzione urinaria.
- Il soggetto presenta un volume di PVR significativo (> 150 mL).
- Secondo quanto determinato dal ricercatore, il soggetto presenta un’incontinenza da stress significativa o un’incontinenza mista da stress/urgenza in cui lo stress è il fattore predominante.
- Il soggetto ha un catetere a dimora o pratica l’autocateterizzazione intermittente
- Il soggetto presenta un’infiammazione cronica come per esempio sindrome della vescica dolorosa/cistite interstiziale, calcoli vescicali sintomatici o qualunque forma presente o passata di cistite da radiazioni.
- Il soggetto ha ricevuto trattamento intravescicale negli ultimi 12 mesi come per esempio tossina botulinica, resiniferatossina, capsaicina. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence and severity of treatment emergent adverse events (TEAEs)
Primary Efficacy Variables
• Change from baseline in mean number of incontinence episodes per 24 hours at EoT
• Change from baseline in mean number of micturitions per 24 hours at EoT |
Incidenza e severità degli eventi avversi derivanti dal trattamento (TEAE)
Variabili di efficacia primarie
• Variazione nel numero medio di episodi di incontinenza ogni 24 ore dalla baseline alla fine del trattamento
• Variazione nel numero medio di episodidi minzione ogni 24 ore dalla baseline alla fine del trattamento
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Vital signs
• Laboratory test
• ECG parameters
• PVR
|
• Segni vitali
• Test di laboratorio
• Parametri ECG
• Resistenza vascolare polmonare (Pulmonary Vascular Resistance - PVR)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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) | Yes |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 188 |
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 | No |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Denmark |
Estonia |
Finland |
France |
Germany |
Greece |
Hong Kong |
Hungary |
India |
Indonesia |
Italy |
Philippines |
Latvia |
Lithuania |
Malaysia |
Mexico |
Netherlands |
New Zealand |
Norway |
Peru |
Poland |
Romania |
Russian Federation |
Ukraine |
Czech Republic |
Korea, Republic of |
Singapore |
Slovakia |
Slovenia |
South Africa |
Spain |
Sweden |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
|
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
|
LVLS |
Ultima visita dell'ultimo soggetto in studio |
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |