Clinical Trials Register

Summary
EudraCT Number:	2017-000605-20
Sponsor's Protocol Code Number:	FFIS/2017/01/SLT
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-05-29
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2017-000605-20

A.3

Full title of the trial

PERIPHERAL TRANSCUTANEOUS NEUROMODULATION OF THE POST-TIBIAL NERVE (T-PTNS) FOR SOLIFENACIN 10mg. IN THE TREATMENT OF HYPERACTIVE BLADDER SYNDROME: NON-INFERIORITY PHASE IV RANDOMIZED CLINICAL TRIAL

NEUROMODULACION TRANSCUTANEA PERIFÉRICA DEL NERVIO TIBIAL POSTERIOR (T-PTNS) FRENTE A SOLIFENACINA 10mg. EN EL TRATAMIENTO DEL SÍNDROME DE VEJIGA HIPERACTIVA: ENSAYO ALEATORIO FASE IV DE NO INFERIORIDAD

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

PERIPHERAL TRANSCUTANEOUS NEUROMODULATION OF THE POST-TIBIAL NERVE (T-PTNS) FOR SOLIFENACIN 10mg. IN THE TREATMENT OF HYPERACTIVE BLADDER SYNDROME: NON-INFERIORITY PHASE IV RANDOMIZED CLINICAL TRIAL

A.3.2

Name or abbreviated title of the trial where available

SoliTens

A.4.1

Sponsor's protocol code number

FFIS/2017/01/SLT

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	FFIS
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
B.5.2	Functional name of contact point	UICEC
B.5.3	Address:
B.5.3.1	Street Address	Luis Fontes Pagan 9, 1 planta
B.5.3.2	Town/ city	Murcia
B.5.3.3	Post code	30003
B.5.3.4	Country	Spain
B.5.4	Telephone number	34968359763
B.5.5	Fax number	34968359777/381289
B.5.6	E-mail	lola.serna@carm.es

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vesicare
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SOLIFENACIN
D.3.9.1	CAS number	242478-38-2
D.3.9.2	Current sponsor code	FFIS/2017/01/SLT
D.3.9.3	Other descriptive name	SOLIFENACIN SUCCINATE
D.3.9.4	EV Substance Code	SUB21028
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Overactive Bladder Syndrome

Síndrome de vejiga hiperactiva

E.1.1.1

Medical condition in easily understood language

Urinary incontinence

Incontinencia urinaria

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To determine if the T-PTNS is not inferior in the short term (3 months) to one of the usual pharmacological treatments (Solifenacin) in the treatment of SVHI and with respect to the percentage of patients that improve 50% any of the 3 signs (Urinary frequency, diurnal / nocturnal frequency, urgency and urinary incontinence).
- To determine prognostic factors associated with insufficient improvement (less than 50% in the 3 main signs of SVHI (urinary frequency, urgency and urinary incontinence frequency) after treatment with T-PTNS and Solifenacin.

- Determinar si la T-PTNS no es inferior en el corto plazo (3 meses) a uno de los tratamientos farmacológicos habituales (la Solifenacina) en el tratamiento del SVHI y con respecto al porcentaje de pacientes que mejoran un 50% alguno de los 3 signos principales del síndrome (frecuencia miccional diurna/nocturna, urgencia e incontinencia urinaria).
-Determinar factores pronósticos asociados con la insuficiente mejora (inferior al 50% en los 3 signos principales del SVHI (frecuencia miccional diurna/nocturna, urgencia e incontinencia urinaria) tras el tratamiento con T-PTNS y Solifenacina.

E.2.2

Secondary objectives of the trial

- To determine the short-term (3-month) effectiveness of T-PTNS versus Solifenacin in patients with SVHI with respect to: quality of life associated with overactive bladder and incontinence, change in urodynamic parameters and perception Subjective change.
- To determine the safety of the application of T-PTNS against Solifenacin in patients with SVHI with respect to the number of adverse effects produced.
- To determine prognostic factors associated with insufficient subjective improvement (less moderate change) after treatment of SVHI with T-PTNS and Solifenacin.

-Determinar la efectividad a corto plazo (3 meses) de la T-PTNS frente a la Solifenacina en pacientes con SVHI con respecto a: la calidad de vida asociada a la vejiga hiperactiva y la incontinencia, el cambio de los parámetros urodinámicos y la percepción subjetiva de cambio.
-Determinar la seguridad de la aplicación de la T-PTNS frente a la Solifenacina en pacientes con SVHI con respecto al número de efectos adversos producidos.
- Determinar factores pronósticos asociados con la insuficiente mejora subjetiva (menor de moderado cambio) tras el tratamiento del SVHI con T-PTNS y Solifenacina.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Women> 18 years, diagnosed with SVHI for at least 6 months of evolution and who have taken Beta 3 agonists.

Mujeres >18 años, diagnosticadas de SVHI durante al menos 6 meses de evolución y que hayan tomado Beta 3 agonistas.

E.4

Principal exclusion criteria

1) Patients who can contribute biased information: have previously consumed and abandoned anticholinergic drugs due to lack of efficacy or side effects; Suffering from overactive bladder of neurogenic origin (multiple sclerosis, Parkinson's, spinal cord injury); Present cystocele or any prolapse of pelvic organs grade> 2 according to POP-Q classification (39).
2) Patients who may become worse with the interventions envisaged in the study: being a pacemaker-ICD; Who can not take anticholinergics (for hypersensitivity, megacolon, myasthenia gravis, narrow-angle glaucoma); With cutaneous alterations in lower extremities that prevent the placement of electrodes on the surface; Pregnant women or who may be pregnant during the duration of the clinical trial ..

1) Pacientes que puedan aportar una información sesgada: haber consumido y abandonado previamente fármacos anticolinérgicos por falta de eficacia o efectos secundarios; padecer vejiga hiperactiva de origen neurogénico (esclerosis múltiple, Parkinson, lesiones medulares); presentar cistocele o cualquier prolapso de órganos pélvicos grado > 2 según la clasificación de POP-Q (39).
2) Pacientes que puedan empeorar con las intervenciones previstas en el estudio: ser portador de marcapasos-DAI; que no puedan tomar anticolinérgicos (por hipersensibilidad, megacolon, miastenia gravis, glaucoma de ángulo estrecho); con alteraciones cutáneas en extremidades inferiores que impidan la colocación de electrodos en superficie; mujeres embarazadas o que puedan estarlo durante la duración del ensayo clínico..

E.5 End points

E.5.1

Primary end point(s)

Occurrence of a relevant reduction (equal or greater than 50%) in any of the 3 main signs of SVHI (urinary frequency, diurnal / nocturnal frequency, urgency and urinary incontinence). The three signs will be measured with a voiding diary of 3 days in the baseline study weeks and the completion of the first and third month. 3-day urination diaries are a reliable tool and have been shown to be sensitive to change.

The 3-day voiding diary (DM3d) has been validated in Spain in the evaluation of STUI in women, and is available through the website of the Spanish Association of Urology

Ocurrencia de una reducción relevante (igual o mayor del 50%) en alguno de los 3 signos principales del SVHI (frecuencia miccional diurna/nocturna, urgencia e incontinencia urinaria). Los tres signos se medirán con un diario miccional de 3 días en las semanas del estudio basal y la que se cumplan el primer y tercer mes. Los diarios miccionales de 3 días son una herramienta fiable y que han mostrado ser sensibles al cambio .

El diario miccional de 3 días (DM3d) ha sido validado en España en la evaluación de STUI en mujeres, y se encuentra disponible a través de la página de la Asociación Española de Urología.

E.5.1.1

Timepoint(s) of evaluation of this end point

During three days the three following months

Durante tres días los primeros tres meses

E.5.2

Secondary end point(s)

1. Urodynamic changes occurring at 3 months in relation to the following parameters: (i) Mical volume at which the first uninhibited contraction originates, in case of detrusoric hyperactivity; (Ii) extent of uninhibited contractions; (Iii) Total bladder capacity (iv) Post-admixture; V) Flowmetry: Qmax, mean Q, time of urination. All these parameters will be measured with instruments calibrated and available in each center for urodynamic studies.

2. Perception of change in treatment over each of the 3 main signs of overactive bladder syndrome (frequency, nocturia, urinary incontinence), scored by the patient on a valid and reliable seven-point scale (markedly worse, moderately worse , Slightly worse, equal, slightly better, moderately better and markedly better). Change will be considered when the patient has moderately or markedly improved. Insufficient improvement in the rest of the answers.

3. Number of adverse effects related to the mouth per month and 3 months of follow-up. At each visit, a blind assessor will determine if there was any adverse effect during the previous month. The effects may be related to deterioration in dry mouth (or xerostomia), salivary flow and oral quality of life compared to basal.
Xerostomia will be measured using a validated questionnaire (36) consisting of 7 items related to oral dryness and a last item where the patient scores overall their level of dryness, this questionnaire that allows us to measure the intensity of oral symptoms using Scales Analog Visuals (EVAs). The amount of saliva will be measured with the non-stimulated salivary flow test. This test allows to know changes in the secretion and if it performs a normal or low salivary secretion. Oral quality of life will be measured using the Oral Health Impact Profile (OHIP-14) test in its Spanish-validated version. It is presented in the form of questions about everyday situations that the patient must respond to as often as they happen.

4. Number of other adverse effects. It will measure the new onset of tingling in legs constipation, dyspepsia, vomiting, heartburn, dry eyes, and others. All of them will be measured from the patient's self-report.

1. Cambios urodinámicos acontecidos a los 3 meses en relación a los siguientes parámetros: i)Volumen miccional al cual se origina la primera contracción no inhibida, en caso de hiperactividad detrusoriana; ii) Amplitud de las contracciones no inhibidas; iii) Capacidad vesical total iv) Residuo postmiccional; v) Flujometría: Qmax, Q medio, tiempo de micción. Todos estos parámetros serán medidos con instrumentos calibrados y disponibles en cada centro para la realización de estudios urodinámicos.

2. Percepción de cambio acontecido con el tratamiento sobre cada uno de los 3 signos principales del síndrome de vejiga hiperactiva (frecuencia, nocturia, incontinencia urinaria), puntuada por el paciente sobre una escala válida y fiable de siete puntos (marcadamente peor, moderadamente peor, ligeramente peor, igual, ligeramente mejor, moderadamente mejor y marcadamente mejor). Se considerará cambio cuando el paciente haya mejorado moderada o marcadamente. Insuficiente mejora en el resto de respuestas.

3. Número de efectos adversos relacionados con la boca al mes y 3 meses de seguimiento. En cada visita, un evaluador ciego determinará si existió algún efecto adverso durante el mes anterior. Los efectos podrán ser relativos a un deterioro en la sequedad de boca (o xerostomía), el flujo salival y la calidad de vida oral comparada con basal.
La xerostomía se medirá mediante un cuestionario validado formado por 7 ítems relacionados con la sequedad oral y un último ítem donde el paciente puntúa de forma global su nivel de sequedad, este cuestionario que nos permite medir la intensidad de los síntomas orales mediante Escalas Visuales Analógicas (EVAs). La cantidad de saliva se medirá con el test de flujo salival no estimulado . Este test permite saber cambios en la secreción y si realiza una secreción salival normal o baja. La calidad de vida oral se medirá con el test Perfil de Impacto de Salud Oral (OHIP-14) en su versión validada al español . Se presenta en forma de preguntas sobre situaciones de su día a día, que el paciente debe responder según con la frecuencia en que le suceden.

4. Número de otros efectos adversos. Se medirá la nueva aparición de hormigueo en piernas estreñimiento, dispepsia, vómitos, pirosis, sequedad de ojos, y otros. Todos ellos serán medidos a partir del autoinforme del paciente.

E.5.2.1

Timepoint(s) of evaluation of this end point

During three days the three following months

Durante tres días los primeros tres meses

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Producto sanitario

Medical device

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

last visit of the last subject undergoing the trial

Última visita del último paciente reclutado

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

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

116

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Ninguna

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-07-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-24

P. End of Trial
P.	End of Trial Status	Ongoing

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