E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Overactive Bladder |
Vejiga hiperactiva |
|
E.1.1.1 | Medical condition in easily understood language |
Overactive Bladder |
Vejiga hiperactiva |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
E.1.2 | System Organ Class | 100000004857 |
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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 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) |
Evaluar la seguridad y la tolerabilidad del tratamiento combinado a largo plazo con solifenacina (5 mg) y Mirabegron (50 mg) en comparación con monoterapias de solifenacina y Mirabegron en sujetos con vejoga hiperactiva |
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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 |
Evaluar la eficacia del tratamiento combinado a largo plazo con solifenacina y Mirabegron
Evaluar los resultados percibidos por el paciente (RPP) durante el tratamiento combinado a largo plazo con solifenacina y 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 |
? El sujeto es hombre o mujer con una edad mínima de 18 años. ? El sujeto está dispuesto y es capaz de rellenar correctamente el diario de micciones y los cuestionarios, y es capaz de tomar sus constantes vitales en su hogar en momentos estipulados, mediante el dispositivo proporcionado por el personal del estudio, y registrar de forma adecuada los valores observados. ? El sujeto presenta síntomas de VH ?húmeda? durante al menos 3 meses. |
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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; |
- Hay una causa neurológica para la hiperactividad del detrusor del paciente (p. ej., vejiga neurogénica, neuropatía diabética o sistémica o enfermedad del sistema neurológico central, como esclerosis múltiple y enfermedad de Parkinson). - El sujeto tiene inflamación crónica como síndrome de dolor vesical o cistitis intersticial, cálculos vesicales sintomáticos o cualquier cistitis por radiación previa o presente. - El sujeto sufre disfunción hepática entre moderada y grave. - El sujeto sufre de disfunción renal grave. - El sujeto tiene un ECG con una anomalía clínicamente significativa. - El sujeto padece una enfermedad maligna o posee historia de cáncer (excepto cáncer de piel no invasivo) en los 5 años previos a la selección. - El sujeto tiene un intervalo QTcF > 450 ms si es hombre o > 470 ms si es mujer, o sufre riesgo de prolongación del QT (p. ej., antecedentes familiares de síndrome del QT largo, hipopotasemia). - El sujeto sufre de hipertensión grave, definida como una tensión arterial sistólica media ? 180 mmHg y/o una tensión arterial diastólica media ?110 mmHg en posición sentada. - En opinión del investigador, el sujeto sufre una obstrucción del flujo urinario clínicamente significativa, con riesgo de retención urinaria. - El sujeto tiene un VRP significativo (>150 ml). - El sujeto padece incontinencia de esfuerzo o una combinación de incontinencia de esfuerzo y de urgencia combinadas, con el esfuerzo como factor predominante según el criterio del investigador. - El sujeto lleva una sonda urinaria permanente o se somete autocateterismo intermitente. - El sujeto muestra signos de infección del tracto urinario (ITU), inflamación crónica como cistitis intersticial, cálculos vesicales , cistitis por radiación previa o padece una enfermedad pélvica maligna. - El sujeto ha recibido tratamiento intravesical en los últimos 12 meses, por ejemplo, con toxina botulínica, resiniferatoxina, capsaicina |
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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 |
- Incidencia y gravedad de los acontecimientos adversos aparecidos durante el tratamiento (AAAT)
Variables de eficacia principales ? Cambio respecto a la situación basal en la media de episodios de incontinencia por periodo de 24 horas en el FdT ? Cambio respecto a la situación basal en la media de micciones por periodo de 24 horas en el FdT |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
EoT |
FdT (fin de tratamiento) |
|
E.5.2 | Secondary end point(s) |
? Vital signs ? Laboratory test ? ECG parameters ? PVR |
? Constantes vitales: ? Pruebas de laboratorio: ? Parámetros del ECG ? VRP |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
EoT |
FdT (fin de tratamiento) |
|
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 | 8 |
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 |
Belgium |
Bulgaria |
Canada |
China |
Denmark |
France |
Greece |
Italy |
Netherlands |
New Zealand |
Norway |
Romania |
Slovakia |
Sweden |
Argentina |
Australia |
Brazil |
Chile |
Colombia |
Czech Republic |
Estonia |
Finland |
Germany |
Hong Kong |
Hungary |
India |
Indonesia |
Korea, Republic of |
Latvia |
Lithuania |
Malaysia |
Spain |
Thailand |
Mexico |
Peru |
Philippines |
Poland |
Russian Federation |
Singapore |
Slovenia |
South Africa |
Taiwan |
Turkey |
Ukraine |
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 |
Última visita del último paciente |
|
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 |