Clinical Trials Register

Summary
EudraCT Number:	2018-001448-78
Sponsor's Protocol Code Number:	Cyst2018_01
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-10-25
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

2018-001448-78

A.3

Full title of the trial

Single-site, open, randomized clinical trial to assess the non-inferiority of
Cysticlean® versus Fosfomicina in the treatment of cystitis in women in
Spain.

Ensayo clínico unicéntrico, abierto y con asignación aleatoria para valorar
la no inferioridad de Cysticlean® comparado con Fosfomicina en el
tratamiento de la cistitis en mujeres en España.

A.3.1

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

Single-site, open, randomized clinical trial to assess the non-inferiority of Cysticlean® versus Fosfomicina in the treatment of cystitis in women in Spain.

Ensayo clínico unicéntrico, abierto y con asignación al azar para valorar la no inferioridad de Cysticlean® comparado con Fosfomicina en el tratamiento de la cistitis en mujeres en España.

A.4.1

Sponsor's protocol code number

Cyst2018_01

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	Vita Green Europa S.A.
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Vita Green Europa S.A.
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	Vita Green Europa S.A.
B.5.2	Functional name of contact point	Dr. Xavier Gras
B.5.3	Address:
B.5.3.1	Street Address	Tuset 19
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08006
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034932695160
B.5.6	E-mail	xavier.gras@vitagreen.com

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	Cysticlean
D.2.1.1.2	Name of the Marketing Authorisation holder	Vita Green Europa SA
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.3.1	Product name	Cysticlean
D.3.2	Product code	Cyst
D.3.4	Pharmaceutical form	Capsule
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	cranberry extract
D.3.9.2	Current sponsor code	Cyst2018_01
D.3.9.3	Other descriptive name	CRANBERRY
D.3.9.4	EV Substance Code	SUB20559
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	250
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	Yes
D.3.11.13.1	Other medicinal product type	Medical device, class IIa.
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Fosfomycin
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.3.1	Product name	Fosfomycin
D.3.2	Product code	Fos
D.3.4	Pharmaceutical form	Capsule
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	FOSFOMYCIN TROMETAMOL
D.3.9.2	Current sponsor code	Fosfomycin
D.3.9.4	EV Substance Code	SUB02263MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
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

Urinary Tract Infection (UTI)

Infecciones urinarias

E.1.1.1

Medical condition in easily understood language

Urinary Tract Infection (cystitis)

Infección urinaria (cistitis)

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10011790
E.1.2	Term	Cystitis escherichia
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assessment of non-inferiority of Cysticlean® versus Fosfomycin in the treatment of cystitis caused by Escherichia coli in women.

Demostrar la no inferioridad clínica de Cysticlean® con respecto a Fosfomicina en el tratamiento de la cistitis provocada por Escherichia Coli en mujeres.

E.2.2

Secondary objectives of the trial

Assessment of the incidence of patients with resistance to Fosfomycin in the overall sample.

Determinar la incidencia de pacientes con resistencia a Fosfomicina en el global de la muestra.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Women aged between 18 and 64 years.
2. With at least of two of the following signs / symptoms of cystitis: Dysuria, Stinging, Hematuria, Frequent, Urinary urgency
3. Cystitis caused by Escherichia coli
4. Written informed consent to participate in this clinical trial.

1. Mujeres con edades comprendidas entre los 18 y 64 años.
2. Con al menos dos de los siguientes signos/síntomas de cistitis: Disuria, Escozor, Hematuria, Polaquiuria, Urgencia miccional
3. Cistitis causada por Escherichia Coli
4. Que otorgan su consentimiento informado por escrito para participar
en este ensayo clínico.

E.4

Principal exclusion criteria

1. Malaise
2. Currently receiving or has received antibiotics for any reason in the last month before entering the study
3. Active treatment with warfarin
4. Allergy to cranberry or any component of Cysticlean® or Fosfomycin
5. History of repeated episodes of acute pyelonephritis during the last year
6. Chills, malaise, fever or temperature higher than 37°C
7. Known morphological abnormalities of the urinary tract
8. Patients with known coagulation disorder
9. Women no to take highly effective contraceptive
10. Immunocompromised patients
11. Patients with urinary tract infection that is not caused by Escherichia coli
12. Patients with advanced cancer or with treatment
13. Patients with severe renal impairment
14.Patients undergoing hemodialysis
15. Patients who are allergic to acetylsalicylic acid
16. Patients taking metocloparamida
17. Participation in another interventional clinical study that could interfere with the results of this trial
18. In the investigator's opinion, is unable to meet the requirements of the study

1. Malestar general
2. Que esté recibiendo actualmente o que haya recibido tratamiento antibiótico por cualquier motivo en el último mes antes de entrar en el estudio
3. Pacientes con tratamiento activo con warfarina
4. Alergia al arándano rojo o alguno de los componentes de Cysticlean® o Fosfomicina
5. Antecedentes de episodios repetidos de pielonefritis aguda en el último año
6. Escalofríos, decaimiento, febrícula o temperatura mayor de 37ºC
7. Alteraciones morfológicas conocidas del tracto urinario
8. Pacientes con alteración conocida de la coagulación
9. Mujeres que no tomen medidas anticonceptivas altamente efectivas que den lugar a una tasa de embarazo baja. ( P.e. menos de 1% al año)
10. Pacientes inmunocomprometidos
11. Pacientes con infección del tracto urinario que no esté causada por Escherichia Coli
12. Pacientes con cáncer en tratamiento o avanzado
13. Pacientes con insuficiencia renal grave
14. Pacientes sometidos a hemodiálisis
15. Pacientes con alergia al ácido acetil-salicílico
16. Pacientes que tomen metocloparamida
17. Participación en otro estudio clínico intervencionista que podría interferir con los resultados de este ensayo
18. En opinión del investigador, no es capaz de cumplir los requisitos del estudio

E.5 End points

E.5.1

Primary end point(s)

Percentage of patients without "treatment failure", defined failure as (presence of at least one of the following):
- Patient reported symptoms / signs of cystitis persist during the test
- Patient should take a new dose of Fosfomycin at some point during the study
- Change of treatment for the cystitis during the study
- Escherichia coli positive urine culture (>100.000 cfu) at the end of the trial

Porcentaje de pacientes que no presenten fracaso de tratamiento, definido el fracaso como (presencia de al menos uno de los siguientes):
- Que la paciente reporte que los síntomas/signos de cistitis persisten durante el ensayo
- Que la paciente deba tomar una nueva dosis de Fosfomicina en algún momento durante el ensayo
- Cambio de tratamiento para la cistitis durante el ensayo
- Urocultivo positivo a Escherichia Coli al final del ensayo con más de 100.000 colonias.

E.5.1.1

Timepoint(s) of evaluation of this end point

At 2 months

A los 2 meses

E.5.2

Secondary end point(s)

Percentage of patients with resistance to Fosfomycin in the overall sample.

Porcentaje de pacientes con resistencia a Fosfomicina en el global de la muestra.

E.5.2.1

Timepoint(s) of evaluation of this end point

At 2-3 days

A los 2-3 días

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

Yes

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

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

2 months after initiation of the treatment.

2 meses tras el inicio del tratamiento.

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:

128

F.1.3

Elderly (>=65 years)

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

128

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

2018-11-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-29

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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