Clinical Trials Register

Summary
EudraCT Number:	2018-000913-19
Sponsor's Protocol Code Number:	BILA-3818/PD
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:	2018-04-09
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

2018-000913-19

A.3

Full title of the trial

Phase IV, single centre, randomised, open-label, two-period, two-way crossover clinical trial to assess the efficacy of Bilastine 20mg in the suppression of wheal and flare induced by intradermal histamine in healthy volunteers under fasted and fed conditions.

Ensayo clínico fase IV, unicéntrico, aleatorizado, abierto, dos períodos, cruzado, para valorar la eficacia de bilastina 20 mg en la supresión de la pápula y eritema inducido por histamina intradérmica en voluntarios sanos en condiciones de ayunas y con comida.

A.3.1

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

Efficacy of Bilastin in reduction of histaine-induce skin reactivity in healthy volunteers under fasted and fed conditions.

Eficacia de Bilastina en la reducción de la reactividad cutánea inducida por histamina en pacientes sanos en condiciones de ayunas y con comida.

A.4.1

Sponsor's protocol code number

BILA-3818/PD

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	FAES FARMA, 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	FAES FARMA, 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	FAES FARMA, S.A.
B.5.2	Functional name of contact point	Clinical Research Director
B.5.3	Address:
B.5.3.1	Street Address	Avda. Autonomia 10
B.5.3.2	Town/ city	Leioa / Vizcaya
B.5.3.3	Post code	48940
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034944818300
B.5.5	Fax number	0034944818309
B.5.6	E-mail	ccampo@faes.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	BILAXTEN
D.2.1.1.2	Name of the Marketing Authorisation holder	FAES FARMA, 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	BILASTINE
D.3.9.1	CAS number	202189-78-4
D.3.9.2	Current sponsor code	F-96221-BM1
D.3.9.3	Other descriptive name	BILASTINE
D.3.9.4	EV Substance Code	SUB37845
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	20
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

ALLERGIC RHINOCONJUNTIVIS AND CHRONIC URTICARIA

RINOCONJUNTIVITIS ALÉRGICA Y URTICARIA CRONICA

E.1.1.1

Medical condition in easily understood language

ALLERGIC RHINOCONJUNTIVIS AND CHRONIC URTICARIA

RINOCONJUNTIVITIS ALÉRGICA Y URTICARIA CRONICA

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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 compare the efficacy of Bilastine 20 mg administered orally under fasted and fed conditions (moderate-fat meal) in reduction of histamine-induced skin reactivity in healthy volunteers, taking into account the first treatment day (Day 1) and steady state (Day 4).

El objetivo primario de este estudio es comparar la eficacia de bilastina 20 mg administrada por vía oral en condiciones de ayunas y con comida (con contenido graso moderado) en la reducción de la pápula y eritema inducida por histamina en voluntarios sanos, teniendo en cuenta el primer día de tratamiento (Día 1) y en estado estacionario (Día 4).

E.2.2

Secondary objectives of the trial

To evaluate the onset of action, duration of the effect, maximum effect and maximum effect time of the wheal & flare surface areas. To evaluate the subjective sensation of itching after histamine inoculation. To assess the safety and tolerability of bilastine after repeated (4 days) single daily oral dose (20mg) administration in young male and female healthy volunteers.

Evaluar el inicio de acción, duración del efecto, máximo efecto y tiempo de máximo efecto en la superficie de las áreas de la pápula y eritema. Evaluar la sensación subjetiva de picor después de la inoculación de histamina. Evaluar el perfil de seguridad y tolerabilidad de la bilastina después de la administración repetida (4 días) de una dosis única oral diaria (20 mg) en voluntarios sanos.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Subjects of either gender (male or female) aged ≥18 and ≤ 45 years at the time of the enrolment. 2 Subjects free from organic or psychic conditions. 3 Medical records and physical examination at screening normal. 4 No clinically significant abnormalities in haematology, biochemistry, serology (Ag HBs, HC, antibodies, HIV antibodies) and urine tests. 5 Vital signs and electrocardiogram record within normal range. 6 Body weight within normal range (BMI ≥ 18.0 and < 28.0 kg/m2) expressed as weight (kg) / height (m2). 7 Subjects must be willing to use a medically acceptable barrier method of contraception throughout the study. Hormonal contraceptives and IUDs are not permitted. 8 Induced wheal area values within the reference range of the Research Institute [0.5521 cm2 – 2.5941 cm2], in the histamine skin reaction test performed during the selection. 9 Free acceptance to participate in the study by means of a signed informed consent form approved by the Ethics Committee of the Hospital (CEIC).

1 Sujetos de ambos sexos (hombre o mujer) con edad ≥18 y ≤ 45 años en el momento de ser incluídos. 2 Sujetos libres de condiciones orgánicas o psíquicas. 3 Historia médica y exámen físico normales en la selección. 4 No anomalías clínicamente significativas en hematología, bioquímica, serología (Ag HBs, HC, anticuerpos, anticuerpos del VIH) y pruebas de orina. 5 Signos vitales y electrocardiograma dentro de los valores normales. 6 Peso corporal dentro de los valores normales (IMC ≥ 18,0 y < 28,0 kg/m2) expresado el peso (kg) / altura (m2). 7 Los sujetos deben estar dispuestos a usar métodos anticonceptivos de barrera médicamente aceptables a los largo del estudio. Los anticonceptivos hormonales y DIUs no están permitidos. 8 Valores del área de pápula inducida dentro del rango de referencia del Instituto de Investigación [0,5521 cm2 - 2,5941 cm2], en la prueba de reacción de la piel con histamina realizada durante la selección. 9 Aceptación libre para participar en el estudio mediante la firma un formulario de consentimiento informado y aprobado por el Comité de Ética del Hospital (CEIC).

E.4

Principal exclusion criteria

1 Background of allergy, idiosyncrasy or hypersensitivity to drugs or any related products (including excipients of the formulations). 2 Heavy consumer of stimulating drinks (>5 cups of coffee, tea, chocolate or cola drinks per day). 3 Background History of alcohol dependence or drug abuse in the last 5 years or daily consumption of alcohol > 40 gr/day for men or 24 gr/day for women. 4 Intake of any medication within 2 weeks prior taking the study treatment (except for use of paracetamol in short-term symptomatic treatments, according to the investigator criteria), including over-the-counter products (including natural food supplements, vitamins and medicinal plants products). 5 Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results. 6 Positive results for abuse drugs in urine test or ethanol in breath test. 7 Background or clinical evidence of cardiovascular, respiratory, renal, hepatic, endocrine, gastrointestinal, haematological, neurological disease or other chronic diseases. 8 Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. 9 Females with positive results from the pregnancy test or breast-feeding. 10 Smokers (refrained from any tobacco usage, including smokeless tobacco, nicotine patches, electronic cigarettes, etc.) for 6 months prior to the study medication intake. 11 To have participated in another clinical trial during the 3 months prior to study start in which an investigational drug or a commercially available drug was tested. 12 To have donated blood within the 4 weeks period before inclusion in the study. 13 Mentally or legally incapacitated at screening. 14 Unwillingness or inability to follow the procedures outlined in the protocol. 15 Any condition that, in the opinion of the investigator, may jeopardise the trial conduct according to the protocol. 16 History of difficulty in swallowing. 17 Positive dermographism.

1 Antecedentes de alergia, idiosincrasia o hipersensibilidad a medicamentos o productos relacionados (incluidos excipientes de las formulaciones). 2 Gran consumidor de bebidas estimulantes (> 5 tazas de café, té, chocolate o bebidas de cola por día). 3 Antecedentes de dependencia del alcohol o abuso de drogas en los últimos 5 años o consumo diario de alcohol > 40 gr/día para hombres o 24 gr/día para mujeres. 4 Ingesta de cualquier medicamento dentro de las 2 semanas previas al tratamiento del estudio (excepto el uso de paracetamol en tratamientos sintomáticos a corto plazo, de acuerdo con los criterios del investigador), incluidos productos de venta libre (incluidos suplementos alimenticios naturales, vitaminas y plantas medicinales). 5 Resultados positivos del antígeno de superficie de la hepatitis B (AgHBs), del anticuerpo del virus de la hepatitis C (Ab de VHC) o del virus de la inmunodeficiencia humana (VIH). 6 Resultados positivos por drogas de abuso en la prueba de orina o etanol en la prueba de aliento. 7 Antecedentes o evidencia clínica de enfermedades cardiovasculares, respiratorias, renales, hepáticas, endocrinas, gastrointestinales, hematológicas, neurológicas u otras enfermedades crónicas. 8 Problemas hereditarios raros de intolerancia a la galactosa, deficiencia de lactasa de Lapp o malabsorción de glucosa-galactosa. 9 Mujeres con resultados positivos de la prueba de embarazo o en periodo de lactancia. 10 Fumadores (absteniéndose de cualquier consumo de tabaco, incluido el tabaco sin humo, parches de nicotina, cigarrillos electrónicos, etc.) durante 6 meses antes de la ingesta del medicamento del estudio. 11 Haber participado en otro ensayo clínico durante los 3 meses previos al inicio del estudio en el que se probó un fármaco en investigación o un medicamento comercialmente disponible. 12 Haber donado sangre dentro del período de 4 semanas antes de la inclusión en el estudio. 13 Incapacitado mental o legalmente en el momento de la selección. 14 Falta de voluntad o incapacidad para seguir los procedimientos descritos en el protocolo. 15 Cualquier condición que, en opinión del investigador, pueda poner en peligro el desarrollo del ensayo de acuerdo con el protocolo. 16 Historia de dificultad para tragar. 17 Dermografismo positivo.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint will be the mean AUC0͢͢͢͢-24 (± standard deviation) of percentages of reduction versus baseline values of the wheal and flare surface areas in each time point.
The mean AUC0͢͢͢͢-24 (± SD) will be calculated for Day 1 and Day 4 of each group, that is, under fasted and fed conditions.
Baseline value: It is defined as the skin test measurements obtained before the volunteers have been exposed to the study drug, that means pre-dose assessment performed on Day 1 of each period.

La variable principal será el AUC0 24 media (± desviación estándar) de los porcentaje de reducción versus el valor basal del área de la pápula y del eritema obtenidos en cada punto temporal.
AUC0 24 media (± SD) se calculará el Día 1 y Día 4 para cada grupo, es decir en condiciones de ayunas y con comida.
Valor basal: se define como la medición de la prueba cutánea obtenida antes de que los voluntarios hayan estado expuestos al fármaco del estudio, es decir la evaluación previa a la dosis realizada el Día 1 de cada período.

E.5.1.1

Timepoint(s) of evaluation of this end point

From Day 1 up to Day 4 of each group, that is, under fasted and fed conditions.

Desde el Día 1 hasta el Día 4 para cada grupo, es decir en condiciones de ayunas y con comida.

E.5.2

Secondary end point(s)

The mean values of wheal and flare surface areas expressed as percentage (%) of reduction respect to their baseline values in each time points, for Day 1 and Day 4, under fasted and fed conditions.
Onset of action: the first time point (h) where wheal and flare surface areas show statistically significant differences, compared to their baseline values.
Duration of the effect: last time point (h) in which the wheal and flare surface areas show statistically significant differences, compared to their baseline values.
Maximum effect: maximum percentage of reduction of the wheal and flare surface areas.
Maximum effect time: time point (h) in which the maximum percentage of reduction of wheal and flare surface areas is reached.
Itching sensation: percentage of variation (reduction) in the VAS score versus their corresponding baseline values, in each time points and in both groups (fasting and feeding).
All the parameters calculated for wheal and flare surface area values will be applied to itching sensation scores.
Changes in the tolerability parameters (clinical laboratory tests, vital signs recording, ECG parameters) evaluated in terms of clinical relevance.
Incidence of adverse events.

La media de los valores de las áreas de la pápula y eritema expresado como porcentaje (%) de reducción respecto a sus valores basales correspondientes en cada punto temporal, para el Día 1 y Día 4, en condiciones de ayunas y con comida.
Inicio de acción: El primer punto temporal (h) donde el área de la pápula y eritema muestran diferencias estadísticamente significativas, comparados con los valores basales correspondientes.
Duración del efecto: último punto temporal (h) donde el área de la pápula y eritema muestran una diferencia estadísticamente significativa, comparados con los valores basales correspondientes.
Máximo efecto: máximo porcentaje de reducción del área de la pápula y eritema.
Tiempo de máximo efecto: Punto temporal (h) en el cual se observa el máximo porcentaje de reducción del área de la pápula y eritema.
Sensación de picor: cambios (mm) en el VAS respecto a los valores basales correspondientes, en cada punto temporal y en ambos grupos (ayunas y con comida).
Cambios en los parámetros de tolerabilidad (pruebas de laboratorio, constantes vitales, parámetros ECG) evaluados en términos de relevancia clínica.
Incidencia de los efectos adversos.

E.5.2.1

Timepoint(s) of evaluation of this end point

Antihistamine activity will be assessed by measurement of the wheal and flare area induced by histamine skin test before and after a single daily dose treatment of bilastine. Treatment in each period will last 4 days. Skin tests will be performed on Days 1 and Day 4 of each period, at the following time points: pre-dose, +0.5h, +1h, +2h, +4h, +6h, +9h, +12h, +24h. Vital signs (systolic and diastolic pressure, heart rate and axillary temperature) will be evaluated at the following time points: baseline [pre-dose], [+1h], [+4h], [+9h], [+12h], and [+24h] post-drug administration.
Adverse events and concomitant medication will be monitored in a continuous way.

La actividad antihistamínica se evaluará mediante la medición del áerea de la pápula y eritema inducida por la prueba de la piel con histamina antes y después de un tratamiento de dosis única diaria de bilastina. El tratamiento en cada período durará 4 días. Las pruebas cutáneas se realizarán en los días 1 y 4 de cada período, en los siguientes puntos de tiempo: predosis, + 0,5 h, + 1 h, + 2 h, + 4 h, + 6 h, + 9 h, + 12 h, + 24 h. Los signos vitales (presión sistólica y diastólica, frecuencia cardíaca y temperatura axilar) se evaluarán en los siguientes puntos de tiempo: basal [predosis], [+ 1h], [+ 4h], [+ 9h], [+ 12h], y [+ 24h] administración posterior a la medicación.
Los eventos adversos y la medicación concomitante se controlarán de forma continua.

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

E.8.1.6

Cross over

Yes

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

Mismo fármaco en condiciones de ayuno y con comida

Same drug under fasted and fed conditions

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

The end of the study is the last visit and it is established at +24h after the last study drug administration (second period) and should coincide with Day 5 of the second period of bilastine treatment.

El final del estudio es la última visita y se establece a +24 horas después de la última administración de medicamentos del estudio (segundo período) y debe coincidir con el día 5 del segundo período de tratamiento con bilastina.

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 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)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

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.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)

It is not applicable as it is a study in healthy voluntees to evaluate the efficacy of bilastine under fasted and fed conditions.

No es aplicable ya que es un estudio en voluntarios sanos para evaluar la eficacia de bilastina en ayunas y condiciones de alimentación.

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

2018-05-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-04-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-06-30

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