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 |
|
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 efficacy of 2 dose combinations of solifenacin and mirabegron compared to solifenacin and mirabegron monotherapy. |
Evaluar la eficacia de 2 combinaciones de dosis de solifenacina y Mirabegron en comparación con monoterapias de solifenacina y Mirabegron |
|
E.2.2 | Secondary objectives of the trial |
? To evaluate the efficacy of 2 dose combinations of solifenacin and mirabegron compared to placebo ? To evaluate the safety and tolerability of 2 dose combinations of solifenacin and mirabegron compared to solifenacin and mirabegron monotherapy and placebo ? To evaluate the Health Related Outcomes Research (HEOR) outcomes of 2 dose combinations of solifenacin and mirabegron compared to solifenacin and mirabegron monotherapy and placebo ? To investigate the population pharmacokinetics and pharmacokinetic/ pharmacodynamic relationship of 2 dose combinations of solifenacin and mirabegron with solifenacin and mirabegron monotherapies |
? Evaluar la eficacia de 2 combinaciones de dosis de solifenacina y Mirabegron en comparación con placebo ? Evaluar la seguridad y tolerabilidad de 2 combinaciones de dosis de solifenacina y Mirabegron en comparación con monoterapias de solifenacina y Mirabegron y placebo ? Evaluar los resultados percibidos por el paciente (RPP) respecto a 2 combinaciones de dosis de solifenacina y Mirabegron en comparación con monoterapias de solifenacina y Mirabegron y placebo ? Investigar la farmacocinética poblacional y la relación farmacocinética/farmacodinámica de 2 combinaciones de dosis de solifenacina y Mirabegron con monoterapias de 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 (urinary frequency and urgency with incontinence) for at least 3 months; |
? El sujeto es un hombre o mujer de al menos 18 años de edad ? 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 ha tenido síntomas de VH ?húmeda? (frecuencia urinaria y urgencia con incontinencia) durante un mínimo de 3 meses |
|
E.4 | Principal exclusion criteria |
1. In the opinion of the investigator the subject has clinically significant bladder outflow obstruction at risk of urinary retention. 2. Subject has significant PVR volume (> 150 mL). 3. Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator. 4. Subject has a 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). 5. Subject has an indwelling catheter or practices intermittent self-catheterization. 6. Subject has chronic inflammation such as bladder pain syndrome / interstitial cystitis, symptomatic bladder stones or any previous or current radiation cystitis. 7. Subject has received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin. 8. Subject has moderate to severe hepatic impairment 9. Subject has severe renal impairment 10. Subject has a clinically significant abnormal ECG 11. Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening. 12. 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). 13. Subject has severe hypertension, which is defined as a sitting average systolic blood pressure ? 180 mmHg and/or average diastolic blood pressure ? 110 mmHg. |
1. En opinión del investigador, el sujeto sufre una obstrucción del flujo urinario clínicamente significativa, con riesgo de retención urinaria 2. El sujeto tiene un VRP significativo (>150 ml) 3. 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 4. 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) 5. El sujeto lleva una sonda urinaria permanente o practica autocateterismo intermitente. 6. El sujeto tiene inflamación crónica como síndrome de dolor vesical o cistitis intersticial, cálculos vesicales sintomáticos o cualquier cistitis por radiación previa o presente. 7. El sujeto ha recibido tratamiento intravesical en los últimos 12 meses, por ejemplo, con toxina botulínica, resiniferatoxina, capsaicina 8. El sujeto sufre disfunción hepática entre moderada y grave 9. El sujeto sufre de disfunción renal grave 10. El sujeto tiene un ECG con una anomalía clínicamente significativa. 11. 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. 12. 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. e.j., antecedentes familiares de síndrome del QT largo, hipopotasemia 13. El sujeto sufre de hipertensión grave, definida como una tensión arterial sistólica media ?180 mmHg o una tensión arterial diastólica media ?110 mmHg en posición sentada |
|
E.5 End points |
E.5.1 | Primary end point(s) |
? 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 |
? 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 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
EoT |
FdT (fin de tratamiento) |
|
E.5.2 | Secondary end point(s) |
? Change from baseline in mean volume voided per micturition at EoT ? Change from baseline in Symptom Bother as assessed by OAB-q at EoT ? Change from baseline in Subject assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS) at EoT |
? Cambio respecto a la situación basal en la media de volumen evacuado en cada micción en el FdT ? Cambio respecto a la situación basal en el nivel de molestia de los síntomas evaluados mediante el c-VH en el FdT ? Cambio respecto a la situación basal en la evaluación por parte del sujeto en la escala análoga visual de satisfacción con el tratamiento (EAV-ST) en el FdT |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 |
China |
Colombia |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
Greece |
Hong Kong |
Hungary |
India |
Indonesia |
Italy |
Korea, Republic of |
Latvia |
Lithuania |
Malaysia |
Netherlands |
New Zealand |
Norway |
Spain |
Sweden |
Thailand |
Mexico |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
Singapore |
Slovakia |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 16 |
E.8.9.2 | In all countries concerned by the trial days | 0 |