Clinical Trials Register

Summary
EudraCT Number:	2014-001484-12
Sponsor's Protocol Code Number:	BUL-1/EEA
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-07-10
Trial results	View 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

2014-001484-12

A.3

Full title of the trial

Double-blind, randomized, placebo-controlled, phase III trial on the efficacy and tolerability of a 6-week treatment with budesonide effervescent tablets vs. placebo for induction of clinico-pathological remission in adult patients with active eosinophilic esophagitis

Ensayo doble ciego, aleatorizado, controlado con placebo y de fase III sobre la eficacia y la tolerabilidad de un tratamiento de 6 semanas con comprimidos efervescentes de budesonida frente al placebo para la inducción de remisión clinicopatológica en pacientes adultos con esofagitis eosinofílica activa

A.3.1

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

Double-blind (neither physician nor patient knows of the actual treatment which can with or without active substance), randomized (patient will be allocated to a certain treatment group by chance), placebo-controlled (tested against tablets without active substance), phase III study on the efficacy and tolerability of a 6-week treatment with budesonide effervescent tablets vs. placebo for induction of clinico-pathological remission in adult patients with active eosinophilic esophagitis

Ensayo doble ciego (ni el medico ni el paciente saben cual es el tratamiento) , aleatorizado (el paciente será asignado al grupo de tratamiento al azar), controlado con placebo (sustancia inactiva) y de fase III sobre la eficacia y la tolerabilidad de un tratamiento de 6 semanas con comprimidos efervescentes de budesonida frente al placebo para la inducción de remisión clinicopatológica en pacientes adultos con esofagitis eosinofílica activa

A.3.2

Name or abbreviated title of the trial where available

Induction of remission with budesonide effervescent tablets vs. placebo in eosinophilic esophagitis

Induccion a la remision con budesonida vs placebo en esofagitis eosinofílica activa

A.4.1

Sponsor's protocol code number

BUL-1/EEA

A.5.4

Other Identifiers

Name:

EOS-1

Number:

Acronym

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	Dr. Falk Pharma GmbH
B.1.3.4	Country	Germany
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	Dr. Falk Pharma GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SERMES PLANIFICACION S.L
B.5.2	Functional name of contact point	Unidad de Puesta en Marcha
B.5.3	Address:
B.5.3.1	Street Address	C/ Rufino González 14, Esc.1ª-2ºD
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28037
B.5.3.4	Country	Spain
B.5.4	Telephone number	+349134756930
B.5.5	Fax number	+34917542721
B.5.6	E-mail	start-up@sermescro.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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1181
D.3 Description of the IMP
D.3.1	Product name	1 mg budesonide effervescent tablet for orodispersible use
D.3.2	Product code	BUET 1mg
D.3.4	Pharmaceutical form	Effervescent 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	BUDESONIDE
D.3.9.1	CAS number	51333-22-3
D.3.9.4	EV Substance Code	SUB05955MIG
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	1
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Orodispersible tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Active eosinophilic esophagitis

Esofagitis eosinofilica activa

E.1.1.1

Medical condition in easily understood language

Chronic allergic/immune-mediated inflammatory disease of the gullet in its active phase

Enfermedad alérgica/ inmune inflamatoria del esófago en fase activa

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10064220
E.1.2	Term	Eosinophilic esophagitis
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of budesonide effervescent tablets vs. placebo for the induction of clinico-pathological remission in adult patients with active eosinophilic esophagitis (EoE).

Evaluar la eficacia de comprimidos efervescentes de budesonida frente a placebo para la inducción de remisión clinicopatológica en pacientes adultos con esofagitis eosinofílica (EE) activa

E.2.2

Secondary objectives of the trial

-To study safety and tolerability in the form of adverse events and laboratory parameters,
-To assess patients quality of life.
Exploratory:
-To study biomarkers in EoE.

-Estudiar la seguridad y la tolerabilidad en forma de acontecimientos adversos y parámetros analíticos.
-Evaluar la calidad de vida del paciente
-Estudiar los biomarcadores de la EE.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Signed informed consent,
- Male or female patients, 18 to 75 years of age,
- Confirmed clinico-pathological diagnosis of EoE according to established diagnostic criteria ,
- Active symptomatic and histological EoE,
- A documented trial with proton pump inhibitors (PPIs) in order to rule out PPI-responsive esophageal eosinophilia,
- Negative pregnancy test in females of childbearing potential at baseline visit

-Firma del consentimiento informado.
-Pacientes varones o mujeres de 18 a 75 años, ambos inclusive.
-Diagnóstico clinicopatológico confirmado de EE según los criterios diagnósticos establecidos
-EEA sintomática e histológica activa
-Un ensayo documentado con inhibidores de la bomba de protones (IBP) para descartar eosinofilia esofágica sensible a los IBP
-Prueba de embarazo negativa en mujeres en edad fértil en la visita inicial.

E.4

Principal exclusion criteria

- Clinical signs (i.e., acid regurgitation and/or heart burn) and endoscopic signs (at least Los Angeles Classification of Esophagitis Grade A) of gastroesophageal reflux disease (GERD),
- History of abnormal results in case of an optionally performed pH monitoring of the distal esophagus,
- Patients with PPI-responsive esophageal eosinophilia
- Achalasia, scleroderma esophagus, or systemic sclerosis,
- Other clinically evident causes than EoE for esophageal eosinophilia,
- Any concomitant esophageal disease and relevant gastro-intestinal disease (celiac disease, inflammatory bowel disease, oropharyngeal or esophageal bacterial, viral, or fungal infection [candida esophagitis]),
- Any relevant systemic disease (e.g., AIDS, active tuberculosis),
- If careful medical monitoring is not ensured: cardiovascular disease, diabetes mellitus, osteoporosis, active peptic ulcer disease, glaucoma, cataract, or infection,
- Liver cirrhosis or portal hypertension,
- History of cancer in the last five years,
- History of esophageal surgery at any time or of esophageal dilation procedures within the last 8 weeks prior to screening visit,
- Upper gastrointestinal bleeding within 8 weeks prior to screening visit,
- Existing or intended pregnancy or breast-feeding.

-Signos clínicos (es decir, regurgitación ácida y/o acidez de estómago) y signos endoscópicos (al menos Grado A según la clasificación de esofagitis de Los Ángeles) de enfermedad de reflujo gastroesofágico (ERGE).
-Antecedentes de resultados anómalos en caso de un control opcional del pH de la parte distal del esófago.
-Pacientes con EES-IBP
-Acalasia, esclerodermia esofágica o esclerosis sistémica.
-Otras causas clínicamente evidentes distintas de la EE para la eosinofilia esofágica (es decir, enfermedad de Crohn, gastroenteritis eosinofílica, enfermedad del tejido conjuntivo, vasculitis, síndrome hipereosinofílico, enfermedad de injerto contra huésped, respuesta de hipersensibilidad farmacológica, infestación parasitaria [en los últimos 3 meses previos a la visita de la selección]).
-Cualquier enfermedad esofágica concomitante y enfermedad gastrointestinal relevante (celiaquía, enfermedad inflamatoria intestinal, infección orofaríngea o esofágica bacteriana, vírica o fúngica [esofagitis por cándida]).
-Cualquier enfermedad sistémica relevante (p. ej., sida, tuberculosis activa).
-Si el control médico minucioso no está garantizado: enfermedad cardiovascular, diabetes mellitus, osteoporosis, enfermedad por úlcera péptica activa, glaucoma, cataratas o infección.
-Cirrosis hepática o hipertensión portal.
-Antecedentes de cáncer en los últimos 5 años.
-Antecedentes de cirugía esofágica en cualquier momento o de procedimientos de dilatación esofágica en las 8 semanas previas a la visita de selección.
-Embarazo existente o intención de quedarse embarazada o en período de lactancia.

E.5 End points

E.5.1

Primary end point(s)

Rate of patients with clinico-pathological remission

Tasa de pacientes con remisión clinicopatológica

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 6 (LOCF)

semana 6 (LOCF)

E.5.2

Secondary end point(s)

- Rate of patients with histological remission,
- Change from baseline in histology
- Rate of patients with resolution of symptoms (i.e., no or only minimal problems of EoE).

-Tasa de pacientes con remisión histológica
-Cambio en el valor máximo entre el inicio y la semana 6 (LOCF).
-Tasa de pacientes con resolución de los síntomas (es decir, ausencia de problemas o problemas mínimos)

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 6 (LOCF)

semana 6 (LOCF)

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

Yes

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

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

6 week open label phase after 6 weeks of treatment for patients not having reached remission

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Switzerland

E.8.7

Trial has a data monitoring committee

Yes

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

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Patients in remission after 6 weeks of treatment in the double-blind phase or in remission after 6 weeks in the open-label phase may enroll the maintenance of remission study BUL-2/EER.
Otherwise, the treatment after trial end (either after the double-blind phase when a patient is in remission or after follow-up visit as end of the follow-up phase) is left to the investigator?s discretion.

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

2015-08-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-08-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-10-04

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